You're viewing our updated article page. If you need more time to adjust, you can return to the old layout.

REVIEW article

Front. Oncol., 12 September 2025

Sec. Gynecological Oncology

Volume 15 - 2025 | https://doi.org/10.3389/fonc.2025.1664340

Gold nanoparticles in the diagnosis and treatment of ovarian and cervical cancers: a comprehensive understanding

  • 1. Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, China

  • 2. Department of Breast Cancer Center, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China

Article metrics

View details

2,2k

Views

510

Downloads

Abstract

Cervical and ovarian cancers pose a significant global threat to women’s health. Despite substantial medical advances in recent decades, gynecological malignancies remain a leading cause of female mortality, constrained by factors such as multidrug resistance, treatment toxicity, asymptomatic presentation in early stages, and genetic heterogeneity. Gold nanoparticles (AuNPs), leveraging their exceptional biocompatibility and multifunctional capabilities, demonstrate considerable potential across diverse fields including bioimaging, liquid biopsy, photothermal therapy, and targeted chemotherapy, thereby advancing precision oncology. Accordingly, this review synthesizes and analyzes the emerging applications of AuNPs in gynecological tumors over the past five years. Moving beyond superficial descriptions of functional features often limited in previous reviews, it places greater emphasis on elucidating the intrinsic relationships and mechanisms between functions from the perspective of their physicochemical properties. It further highlights the critical importance of AuNPs for constructing integrated diagnostic and therapeutic platforms. Simultaneously, this review provides a balanced examination of the challenges hindering the clinical translation of AuNPs and offers insights and perspectives on addressing these issues. It is anticipated that AuNPs may evolve into highly effective diagnostic and therapeutic strategies in the future.

1 Introduction

Cervical and ovarian cancers represent the most lethal gynecological malignancies, each posing distinct clinical challenges. HPV infection constitutes the primary etiological factor for most cervical carcinomas, thus establishing HPV testing as critical for early screening (1). Organized screening and HPV vaccination provide key prevention strategies, especially in developing nations (2). The protracted asymptomatic latency spanning decades from cervical intraepithelial neoplasia to invasive carcinoma creates significant fertility preservation challenges for reproductive-aged patients, given that radical hysterectomy remain primary therapeutic options (3, 4). Ovarian cancer demonstrates the highest aggressiveness among gynecological malignancies, with its characteristically asymptomatic early-stage presentation resulting in fewer than 50% of patients surviving beyond five years post-diagnosis (5, 6). Molecular heterogeneity, intrinsic chemoresistance, and rapid metastatic dissemination collectively contribute to its elevated mortality (7).

Conventional strategies lack early precision and fail to prevent multidrug resistance, necessitating advanced approaches (8, 9). With advancements in oncology, nanotechnology has emerged as a promising frontier (10, 11). Therapeutically, multifunctional nanoparticle-based drug delivery platforms enable cancer cell-specific targeting while sparing healthy tissues, thereby reducing systemic drug exposure, minimizing toxicity, and delaying resistance emergence (1214). Diagnostically, nanoparticles enhance tumor biomarker detection sensitivity, facilitating earlier clinical intervention (15, 16).

Among diverse nanomaterials, gold nanoparticles (AuNPs) stand out due to exceptional biocompatibility and their defining optical property (17). AuNPs are synthesized through established methods including the Turkevich citrate reduction, biological synthesis using plant/microbial extracts, and physical approaches like laser ablation, enabling precise control over size, morphology, and surface functionalization for biomedical applications (18). Localized Surface Plasmon Resonance (LSPR) arises from collective electron oscillations, generating intense, tunable absorption/scattering for colorimetric sensing and enabling Surface-enhanced Raman scattering (SERS) via electromagnetic “hot spots” for trace analyte detection (19, 20). Critically, LSPR drives efficient light-to-energy conversion, underpinning AuNPs’ efficacy as potent photothermal agents and photosensitizers in photothermal therapy (PTT) and photodynamic therapy (PDT) (21). As the morphology progressively evolves, AuNPs’ amplified surface-area-to-volume ratio enhances biomolecular interactions, while exceptional electrical conductivity (>105 S/m for 20-nm particles) facilitates ultrasensitive detection (18, 22, 23). LSPR “hot spots” also modulate fluorescence and enable fluorescence resonance energy transfer (FRET) (24).

AuNPs’ surfaces are readily functionalized via covalent conjugation, biomolecular assembly, or polymeric encapsulation (e.g., thiol anchoring, amide bonds, click chemistry, electrostatic adsorption) to confer targeting specificity, colloidal stability, and multifunctionality (25, 26). This enables active targeting (antibodies/peptides/aptamers) (27) or passive magnetic guidance (Fe3O4 composites) (28), allowing their use as multimodal contrast agents (MRI/X-ray/OCT) (29). Furthermore, AuNPs exhibit distinct catalytic activity in redox reactions, enabling applications in electrochemical biosensors (30). Collectively, these physicochemical properties underpin AuNPs’ transformative potential in diagnosing and treating gynecological malignancies.

Collectively, AuNPs represent a pivotal milestone in precision medicine, offering transformative potential for timely cancer intervention. The following sections detail the application of AuNPs, critically evaluating their contributions to diagnosing and treating gynecological malignancies to establish a reference framework for clinical practice.

2 AuNPs in cervical cancer

2.1 Diagnosis

2.1.1 Colorimetric detection utilizing AuNPs

Functionalized AuNPs undergo LSPR peak shifts and visible color changes upon binding target molecules. AuNPs-based colorimetric assays thus exploit this phenomenon to assess levels of cervical cancer biomarkers through readily observable color transitions (31). microRNA-378 is consistently dysregulated in cervical cancer. Run and colleagues developed a colorimetric assay using catalytic hairpin assembly (CHA) and AuNPs for its detection (31). Target miRNA-378 triggers CHA between two hairpin probes, generating polymeric products. Multiple polyadenine blocks on these products adsorb and cross-link AuNPs (~13nm, Citrate-reduced) under acidic conditions, inducing aggregation. This shifts the LSPR, causing a visible color change from red to purple (Figure 1) (31). The assay leverages nucleic acid hybridization specificity, offering operational simplicity, high sensitivity, and strong specificity, with a LOD of 20.7 pM (31).

Figure 1

Diagram illustrating a DNA-based catalytic hairpin assembly (CHA) mechanism involving hairpin structures HP1 and HP2. In the presence of microRNA (miRNA), DNA forms complexes, influencing aggregation behavior. At low pH, reactions lead to sphere formation, depicted as purple circles on the right, and orange spheres on the left with no miRNA. Arrows indicate the flow and interaction of molecules.

Schematic diagram of the detection process of smiRNA378 by colorimetric method based on AuNP design (31).(copyright permission obtained).

Motivated by the high cost of target-specific AuNP functionalization, label-free C-ColAur was developed as an alternative (32). Label-free C-ColAur is a nonspecific detection method leveraging AuNPs color shifts from LSPR. Target binding protects AuNPs from salt-induced aggregation, enabling rapid on-site pathogen screening via visible color changes, particularly in resource-limited settings (32). Applied to cervicovaginal fluid, it shows distinct color changes: AuNPs turn blue in healthy samples but remain unchanged in cancer samples, achieving high diagnostic accuracy (96% sensitivity, 87% specificity; Figure 2) (33). Transmission Electron Microscope (TEM) revealed significantly larger AuNP diameters (250~400nm, Citrate-reduced, Quasi-Spherical) in patients versus controls (15~30nm, Citrate-reduced, Quasi-Spherical), with reduced particle numbers and absence of aggregation in cancer samples (33). Tejaswini et al. proposed that cancer cell membrane components induce aggregation (34). Experimental validation confirmed that synthetic lipids, but not proteins or lipid-protein mixtures, replicated the color or spectral shift when reacted with HAuCl4·3H2O and ascorbic acid, indicating lipid-specific organization drives the mechanism (34).

Figure 2

Diagram showing the process of in-situ formation of gold nanoparticles for colorimetric detection of cervical cancer. It compares a blank sample with pink spheres, a control with blue clusters, and a test with gray circles representing cervical fluid. The term “C-CoIAur” is labeled alongside a figure representing a female, indicating the source of the cervical fluid samples used in the test for cancerous versus healthy samples.

Schematic showing the colorimetric detection of cervical cancer using the label-free “C-ColAur” technique (33).

HR-HPV is the primary cause of cervical cancer. Conventional detection (qPCR, isothermal amplification, dot blot) faces limitations including contamination risk, incomplete subtyping, and high cost (35). AuNP-based colorimetric assays (57.7 ± 4.2nm, Citrate-reduced, Quasi-spherical with dendritic protrusions) enable instrument-free, visual or smartphone-based readout of HPV-16/18, permitting quantitative results acquisition by untrained personnel without specialized equipmen (36). Carlos conjugated AuNPs (21.6 ± 0.1nm, Turkevich) with anti-HPV-16/18 L1 antibodies (37). Applied to 173 cervical samples, infection caused a color shift(red to purple) and LSPR red-shift (523~525 nm to 524~590 nm) (37). The assay detected HPV-16 L1 (linear range: 0.4~2.0μg/mL, LOD: 0.18μg/mL) and HPV-18 L1 (0.2~1.2μg/mL), identifying PCR-missed variants potentially via conserved L1 epitope recognition (37). To expand coverage, Jixue and team developed a multiplexed closed-tube PCR, detecting 17 HPV types (LOD: 0.5copies/μL, linear range: 0~1000copies/μL) with 99.05% accuracy (38).

2.1.2 AuNPs-engineered electrochemical biosensors

Colorimetry lacks micro-scale sensitivity. Electrochemical biosensors convert biorecognition events to electrical signals (39). CEA, SCCA, Ki67, p53, and p16INK4a are key cervical cancer biomarkers (35). Antibody-conjugated AuNPs enable their multiplexed detection. Electrochemical sensors universally use: 1) conductive substrates (Pt/Co/MoS2/WS2/rGO) to amplify AuNPs signals, and 2) engineered porous architectures (SiO2 dendrimers, multilayered nanoparticles, 3D networks) to enhance target capture and conductivity (Table 1) (4042). These AuNPs-centered platforms show diagnostic promise (40). In a recent study, Hiranmoy et al. developed an ultrasensitive electrochemical immunosensor for cervical cancer biomarker p16INK4a detection by modifying a glassy carbon electrode through sequential deposition of graphene oxide and ~70nm spherical AuNPs (43). The sensor utilized cysteamine-glutaraldehyde crosslinking to immobilize p16INK4a monoclonal antibodies on the electrode surface (43). Compared to bare electrodes, Au/rGO-modified electrodes exhibited significantly enhanced peak currents with charge transfer resistance (Rct) reduced from 245 Ω to 14 Ω, demonstrating AuNPs’ capacity to facilitate electron transfer. Clinical serum analysis via square wave voltammetry achieved 100% accuracy with a detection limit of 167 fg/mL and linear range from 500 fg/mL to 100 ng/mL (43). The AuNP-engineered sensor demonstrated exceptional selectivity, storage stability, repeatability, reproducibility and regeneration capability.

Table 1

No Particle size Targe Surface functionalization Highlights of Study Clinical sample LOD Linear range Reference
1 317.4 ± 12.3nm miRNA-21 Thiolation MoS2/AuNPs composite-modified electrode and multilayered nanoneedle structure Artificial serum 38aM 10aM~1uM (41)
2 SCCA Thiolation Bimetallic PtCo nanoframe-modified electrode and dendritic DM-SiO2@AuPt core–shell nanostructures Artificial serum 7.33fM 22.22fM~2.67µM (42)
3 13.2 ± 2.32nm p16INK4a; P53; Ki67 Thiolation; Electrostatic adsorption Schematic of label-free sensing with redox reporters (Cd²+/DAP/MB);3SPCE array/GO/2D WS2/PEI-AuNPs/redox probe Artificial serum 9.38nM; 5.49nM; 0.56nM 0.01~100ng/mL (40)
4 ~16nm α2, 6-sialic acid Electrostatic adsorption ATR-FTIR combined with chemometrics for biosensor-cell interaction signal enhancement. (44)
5 ~75nm p16INK4a Thiolation The Au-rGO material was employed for the first time to detect serum p16INK4a. serum(15) 167fg/mL 500fg/mL~100ng/mL (43)

Research on the detection of serum tumor markers.

Similarly, while colorimetry detects cervical exfoliated cells, its accuracy suffers from subjective visual interpretation of subtle color shifts. AuNP-integrated (~16nm, Citrate-reduced, Spherical, chitosan-coated) photoelectric sensors enhance precision by targeting cancer-specific α2,6-sialic acid overexpression via SNA-conjugated AuNPs (44). Ricardo and team detected diagnostic spectral alterations at 1470, 1456, 1434, 1400, and 1350 cm¹ in cancer-bound complexes using attenuated total reflection fourier-transform infrared spectroscopy (ATR-FTIR) (44). Notably, Ricardo et al. leveraged machine learning (ML), specifically principal component analysis (PCA), to identify sialic acid-associated spectral signatures in cervical cancer cell lines. Orthogonal principal components maximizing data variance were derived, enabling construction of confidence ellipse models that robustly discriminated primary fibroblasts from malignant cells (non-overlapping 95% confidence intervals; p<0.001) (44). This approach establishes a non-invasive diagnostic paradigm for early cervical cancer detection through surface-enhanced infrared absorption (SEIRA) biomarker profiling. (Figure 3).

Figure 3

Four spectral graphs labeled A to D compare absorbance versus wavenumber for different cell lines with and without SNA Bios. All graphs show similar absorbance patterns, with peaks between wavenumbers 1000 and 1200 cm⁻¹. Graph A is SiHa, B is HeLa, C is C33A, and D is Fibroblasts.

Mean ATR-FTIR spectra (baseline corrected and min/max normalized) of control cells and after interaction between SNA biosensors and (A) SiHa; (B) HeLa; (C) C33A; and (D) primary fibroblasts (44).

AuNPs enhance HPV-16 DNA detection by increasing electrode surface area, accelerating electron transfer, and amplifying signals (39, 45). As Table 2 shows, varied electrode designs achieve LODs<0.2fM (4649). Dielectric and photoelectrochemical sensors offer enhanced precision, with maintained functionality during long-term cold storage (46, 48).

Table 2

No Particle size Targe Surface functionalization of AuNPs Highlights of Study Clinical sample LOD Linear range Reference
1 HPV 16 DNA Exhibits strong anti-interference capability in human serum Artificial serum 0.5475 fM 100fM~1000nM (50)
2 HPV-18 DNA Thiolation rGO-MWCNT-AuNPs nanocomposite-functionalized SPCEs Cervical smear 0.05fM 0.01fM~0.01nM (47)
3 16 ± 1nm HPV-16 DNA Thiolation APTES-modified GCE; CP-AuNPs immobilized via phosphate-amine electrostatic adsorption Artificial serum 0.1731fM 100fM~10uM (46)
4 18.9 ± 1.5nm HPV-16 E6/E7 mRNA Thiolation; Covalent bonding LAMP-amplified mRNA; Streptavidin modification; ssDNA-AuNPs targeting; SA-HRP signal amplification Cervical smear(20) 0.08fM 100nM~100uM (48)
5 HPV L1 Electrostatic adsorption PANI electrode with AuNPs deposition; MY11 degenerate probe Cervical smear 0.113nM 1~100 pg/μL (51)
6 ~5nm HPVs Screen-printed photoelectrode array modified with TiO2@AuNPs Positive cervical smear(20); negative cervical smear(20) 0.1copies/μL 0.6~600copies/μL (52)
7 9 ± 1.5nm HPV-18 DNA Covalent bonding SiO2-micro-IDE substrate; APTES-AuNPs dehydration-condensation modification Cervical smear(20) 0.529aM 1aM~100fM (49)
8 ~40nm HPV-16/18 DNA Electrostatic adsorption CuCo2S4-ZnIn2S4-S heterojunction interface; Paper-film composite chip Serum 0.21pM; 42.92pM (53)
9 ~15nm HPV-16 Using SynSed technology as an alternative method for particle transfer in DFM imaging Artificial serum 10fM 0pM~500pM (54)
10 ~50nm HPV-16 Covalent bonding This is the first dual-colorimetric strategy based on AuNPs for detecting double-stranded HPV-16 viral genome. Cervical smear 1.9nM 0.45~6.72nM (45)

Recent advances in HPV detection biosensors.

Lin and colleagues’ paper-based sensor achieves significant cost reduction (<$1.00), miniaturization, and commercial viability (53). Utilizing lateral flow principles, HPV-16/18 DNA hybridizes with probes in a rapid-flow zone, forming circular structures that bind AuNPs (~40nm, Spherical)-polydopamine (PDA). Light irradiation triggers AuNP-mediated photothermal conversion, intensifying thermal response while diminishing photocurrent. Subsequent fluid migration to a slow-flow zone enables CRISPR-Cas12a-mediated DNA cleavage and HPV fragment release, reversing signals (Figure 4) (53). This system detects HPV-16/18 DNA within 30 minutes with high specificity (LOD: 0.21pM and 42.92pM, respectively) (53). However, Lin’s sensor is susceptible to temperature, salt concentration, and reaction time variations due to pre-hybridization nucleic acid cleavage. These factors exacerbate electrical signal transduction limitations, including single-molecule counting inability. To overcome this, Jia and team integrated dark-field microscopy (DFM) imaging, circumventing signal dependency while employing synergistic sedimentation (SynSed) to minimize nanoparticle diffusion (~15nm, Citrate-reduced) (54). This optimized system achieves a LOD of 10 fM.

Figure 4

Illustration of CRISPR-Cas12a system for detecting HPV. Panels A-C depict different reaction stages, showing DNA structures interacting with Cas12a. Graphs illustrate temperature and photothermal changes over time. Panel D shows an overview of the workflow on a chip. Panel E illustrates CRISPR-Cas12a with HPV-16 and HPV-18 DNA pathways. Panel F presents gel electrophoresis results with labeled DNA fragments. Symbols indicate hairpin DNA, arm DNA, Cas12a, crRNA, annular DNA-HPV-18, and Au-PDA-labeled DNA.

Detection steps and interactive signal change process in the (A) initial state, (B) the DNA conformational change state, and (C) CRISPR-Cas12a activation state. (D) Schematic diagram of the proposed lateral flow biosensor. (E) Signal amplification process of the CRISPR-Cas12a-driven dual-readout lateral flow biosensor. (F) Feasibility analysis for the self-assembly process of the annular DNA and trans-cleavage instinct of CRISPR-Cas12a (53). (copyright permission obtained).

Beyond HPV-16 and HPV-18, other high-risk HPV types (31, 56, 59, 68) also contribute to cervical cancer development (35). To address this, platforms incorporating MY11 probes targeting conserved regions of the HPV L1 gene have been integrated with AuNPs-doped detection systems. AuNPs amplify current-voltammetric signals generated by minor nucleotide variations within the L1 conserved regions of HPV-16/31/33/45/58, enabling the construction of HPV genotyping profiles (51). Conversely, an alternative strategy anchors multiple recognition probes within a photoelectrochemical biochip array (PEBA) platform composed of TiO2@AuNPs composites (52). This highly integrated chip-based format achieves an exceptionally low LOD of 0.1 copies/μL, demonstrating high concordance with clinical results (52).

2.1.3 SERS detection based on AuNPs

SERS surpasses electrochemical biosensors in AuNPs-based serological diagnostics by circumventing electrode constraints. As Table 3 shows, platforms utilize: 1) sharpened AuNPs geometries to intensify electromagnetic hotspots, and 2) ordered array chips to enhance spectral reproducibility (5558). However, significant LOD variability exists (e.g., 191.73 fM vs. 10 fM for SCCA in serum) (55, 58), likely stemming from AuNPs morphology and Raman reporter differences (Figure 5).

Table 3

No Particle size Targe Surface functionalization of AuNPs Highlights of Study Clinical sample LOD Linear range Reference
1 ~600nm SCCA; OPN Ag-AuNFs bimetallic nanocomposites with arrow-headed tip nanostructures Serum(150) 191.73fM; 132.97fM 10 pg/mL~9 μg/mL (55)
2 ~45nm B7-H6 Covalent bonding Zwitterion-modified stealth sensor with pH-stable spiky AuNPs Positive serum(9); negative serum(1) 10fM 10fM~10nM (56)
3 ~20nm CpG methyltransferase Site-selective assembly of AuNP arrays on monolayer SiO2 arrays yielding Au@SiO2 array substrates;RCA signal amplification strategy Serum(150) 0.251mU/mL 0.005~50U/mL (57)
4 ~20nm SCCA; CEA Cubic Ag-Au bimetallic nanoparticles integrated on Au@SiO2 array substrates;Pump-free flow via capillary pump/hydrophilic-treated channels;Multichannel parallel auto-detection Positive serum(60); negative serum(30) 10fM; 2fM 1pg/mL~1μg/mL (58)
5 70~80nm p16;Ki-67 Covalent bonding AuNS@Ag nanoflowers enable 20-min slide detection, bypassing ICC staining. Cervical smear (59)
6 ~20nm miRNA21/124/143 SPRi: AuNP-helper probes enhance chip signals; SERS: Triplex Raman reporters hybridize with target miRNAs. 1 fM; 0.8 fM; 1.2 fM 10 fM~100pM (60)
7 40~45nm SERS on single cells/spheroids/DNA + chemometrics (PCA/LDA/SVM) for cervical cancer detection; validated by cytology/HPV PCR/UFLC metabolomics. Cervical smear (61)
8 ~80nm “Hotspot”-rich 3D plasmonic AuNP-nanomembranes: LLISA-assembled monolayers triple-stacked on ITO; optimized with AI. Positive serum(12); negative serum(5) (62)
9 ~25nm A reliable detection protocol was established to obtain highly stable and reproducible serum SERS spectra Positive serum(12); negative serum(24) (63)
10 83 ± 6nm sEV Detection of cancerous exosomes using plasmonic AuNPs nanosheets as SERS substrates combined with CD63 nanoflares Positive serum(11); negative serum(8) 4.7 × 105 particles/mL. 1 × 106~2 × 108particles/mL (64)

Research on the detection of cervical cancer (SERS).

Figure 5

(A) Transmission electron microscopy image of a dark square nanoparticle with rounded corners, measuring 50 nanometers. (B) Scanning electron microscopy image of a complex star-shaped nanostructure with multiple pointed tips, measuring 200 nanometers.

(A) High magnification SEM image of Cube-AuNPs (58); (B) High magnification SEM image of AuNF (55). (copyright permission obtained).

SERS and Surface Plasmon Resonance Imaging (SPRi) are increasingly favored for cervical cancer biomarker detection (Table 3). Yifan and team developed a dual-mode SPRi/SERS biosensor with a polyA capture probe/target miRNA/AuNPs-enhanced probe sandwich architecture (60). This platform concurrently detects miRNA-21/124/143 on a single chip (60). Target hybridization forms ternary complexes where AuNPs enhance SPRi via refractive index modulation while generating SERS hotspots through LSPR (60). Dual-signal redundancy reduces false positives (serum recovery: 90.0–100.2%) (60). This high-throughput platform provides dual-verified nucleic acid detection with clinical utility.

The spatial arrangement of AuNPs in SERS sensors critically determines analytical outcomes. Xingkang et al. engineered a nanoscale monolayer film of uniform AuNPs (83 ± 6nm) to generate evenly distributed dense hotspots, overcoming the random hotspot distribution characteristic of conventional plasmonic colloidal solutions (64). This design prevented heterogeneous electromagnetic signals arising from nanoparticle aggregation while enhancing SERS signal reproducibility and sensitivity (64). Furthermore, integration of CD63 nanoflares with AuNPs created supplemental hotspots that amplified SERS intensity by 4.1-fold (64). The resulting platform exhibited linear detection of cancer exosomes from 1×106 to 2×108 particles/mL with a limit of detection (LOD) of 4.7×105 particles/mL (64).

Artificial intelligence enables more efficient mining of the massive data generated by AuNP probes in SERS sensing analysis, forming the foundation for low-cost nonspecific analysis. Hongmei and team established that 10 ppm serum prevents AuNPs encapsulation while enhancing dispersion homogeneity (63). After screening lasers, they selected 785 nm and 633 nm excitation (excluding 532 nm due to fluorescence interference), achieving 0.9609 spectral cosine similarity at 10 ppm (63). Clinical validation with 36 sera (24 healthy/12 cancer) identified differential peaks at 1201 cm¹ and 1312 cm¹. PCA achieved complete group separation, establishing the first standardized SERS reference library for cervical cancer sera. This methodology provides a robust foundation for clinical SERS translation (63).

Meanwhile, this simultaneously enables unsupervised recognition of cervical cell pathology through AI analysis of non-functionalized gold nanoparticles (nfGNPs). Karunakaran et al. implemented support vector machine (SVM) algorithms to achieve high-precision classification of NRML/HSIL/CSCC specimens (94% ± 0.73% accuracy for single-cell analysis), markedly improving post-PCA specificity with ROC-validated diagnostic progression (AUC >0.98) for cervical lesion stratification (61). In contrast, Diao et al. adopted a PCA-LDA fusion strategy (62). Following Savitzky-Golay filtering with airPLS background correction and min-max normalization, PCA reduced spectral dimensions to 46 principal components retaining 95% of the variance (62). LDA then compressed these into two discriminative factors. This hierarchical approach resolved non-overlapping 95% confidence ellipses observed under singular methods and attained 91.1% accuracy in differentiating exosomes across H8, HeLa, and MCF-7 cell lines (62). The model demonstrated robust diagnostic efficacy, with AUCs ranging from 0.93 to 0.99, and maintained 93.3% overall accuracy in clinical validation (62). It perfectly classified breast and cervical cancer serum exosomes while correctly identifying 80% of healthy samples. This established a non-invasive framework for SERS-driven early cancer detection (62).

2.1.4 AuNPs-enabled innovative imaging strategies

Imaging is vital for non-invasive cervical cancer diagnosis. Tumor-targeting ligand-functionalized AuNPs (e.g., folic acid, oligotyrosine/RGD/NLS peptides) serve as effective contrast agents (65). The tumor microenvironment further enhances AuNPs (50.3 ± 1.1nm, Citrate-reduced, spherical) accumulation, where acidic pH triggers hydrolysis of citraconic anhydride linkages in AuNPs-doxorubicin (DOX) complexes (66).

Radioiodinated AuNPs serve as contrast agents for clinical imaging (MRI/US/CT/PET) (29). Min and colleagues engineered pH-responsive theranostic AuNPs (50.3 ± 1.1nm, Microwave-assisted synthesis, spherical) with PEGylated surfaces and citraconic anhydride-linked DOX (66). At pH 5.5, linker hydrolysis triggers DOX release and electrostatic aggregation (35-nm UV-Vis redshift; TEM-confirmed), amplifying imaging signals (66). Radioiodination achieved 35.4% labeling efficiency, with PET showing 1.37%ID/g tumor uptake at 2h and >38% cancer cell binding (66). Photoacoustic imaging (PAI) generates biological images by detecting photon emissions from contrast agents. AuNPs exhibit exceptional PAI properties due to high photothermal conversion efficiency (66). The Au-UCNP-PEG2k nanocomposite serves as both photodynamic therapy agent and multimodal imaging platform (~5nm, Hydrothermal method, spherical) (67). In vivo studies show superior PAI performance under near-infrared region (NIR) irradiation compared to bare AuNPs, functioning as a trimodal contrast agent for comprehensive tumor diagnostics (Figure 6) (67).

Figure 6

Two thermal images labeled (a) and (b) display temperature variations in blue, yellow, and red, with red areas indicating higher temperatures. Both images feature irregular patterns and are marked with a scale of five millimeters.

PAI of before (a) and after (b) injection 200 µg/mL of Au-UCNPs-DSPE-PEG2K in Balb/c mice (67).

AuNPs enhance lesion identification in laboratory imaging (68). Under DFM, FA-targeted AuNPs@Ag@AgI nanostructures internalized by HeLa cells enable precise spatial localization via amplified light scattering (68). Simultaneously, AuNPs’ plasmonic properties mediate surface energy transfer to fluorescent donors (e.g., TAP, PHEN), inducing controlled fluorescence quenching within cells, supporting development of real-time imaging agents (68).

2.2 Treatment

2 .2.1. AuNPs-based drug delivery systems

AuNPs enable targeted cancer cell eradication via drug and ligand conjugation. Therapeutic payloads encompass Methotrexate (MTX) (69), DOX (66), Paclitaxel (PTX) (70), and luteolin (71). Common cervical cancer targeting ligands comprise Folic Acid (FA), Hyaluronic Acid (HA), and AS1411 aptamer (Table 4). Emerging agents show complementary potential (72). The investigational compound IQ activates TLR7/8-mediated immune responses and NF-κB-dependent apoptosis. When complexed with nucleolin-targeting AS1411 aptamer on AuNPs (IQ-AS1411-AuNPs), MTT assays demonstrated significantly reduced HeLa cell viability (72).

Table 4

No Particle size Surface functionalization of AuNPs Drug Highlights of Study Cell line Toxic Reference
1 ~11nm Thiolation MTX AuNPs with FA modification; High MTX loading (>98.7% EE); GSH-responsive MTX release U-87MG; HeLa; A549; PC3; HEK-293 The MTT results indicate no toxicity. (69)
2 50.3 ± 1.1nm Thiolation; Covalent bonding DOX Citraconic anhydride linker enables pH-responsive DOX release in tumor microenvironment HeLa Considered (66)
3 ~20nm Thiolation PTX One-pot synthesis using PTX as dual reductant/stabilizer; Eco-friendly process without additional chemicals SiHa; HT-29 Considered (70)
4 18.30~21.16nm Thiolation Imiquimod AS1411-mediated selective drug delivery; Enhanced vaginal tissue retention for gynecological cancer therapy HeLa; HEC-1-A; NHDF; Franz No toxicity (72)
5 26.35 ± 2.13nm Thiolation; Covalent bonding DOX pH-responsive DOX release; Dose-dependent cytotoxicity in HeLa cells; Synergistic therapeutic platform for ovarian cancer HeLa A dose-dependent toxicity was observed. (73)

Design of AuNPs for the treatment of cervical cancer (drug delivery).

Beyond ligand-mediated targeting, tumor microenvironment (TME) characterized by hypoxia, low pH, elevated GSH, and ROS, directs AuNPs accumulation. A TME-responsive platform bypasses ligand functionalization, exemplified by GSH-cleavable disulfide-linked AuNPs (~11nm, Brust-Schiffrin, spherical) achieving 98.7% MTX encapsulation for cervical cancer (69). Similarly, DOX-conjugated AuNPs utilize pH-labile hydrazone bonds that hydrolyze selectively in acidic TME conditions, enabling clinically translatable targeted therapy (66, 73).

Toxicity and complexity concerns around chemical stabilizers (e.g., 3MPA/3MPS/PVP) drove Kamini et al. to develop a novel PTX delivery platform (70). Their method synthesizes PTX-AuNPs in one step by adding silver ions to PTX/gold ion suspensions under sunlight (Figure 7), where PTX acts as both therapeutic payload and reducing/stabilizing agent (70). This eliminates pre-synthesized AuNPs and exogenous stabilizers, reducing costs while bypassing conventional drug-loading, though the photochemical mechanism requires further study (70).

Figure 7

Illustration showing the process of paclitaxel functionalized gold nanoparticles. Sunlight irradiates a vial creating the nanoparticles, which are then depicted interacting with cancer cells, leading to cell death.

One pot synthesis of paclitaxel functionalized gold nanoparticles and their anticancer studies (70). (Copyright permission obtained).

2.2.2 Intrinsic antitumor effects of AuNPs

AuNPs exert intrinsic cytotoxicity against cervical cancer cells via apoptosis modulation (72, 74). Concentration-dependent upregulation of pro-apoptotic markers (BAX, p53) and downregulation of anti-apoptotic factors (Bid, BCL-2) occur with concomitant caspase activation (75). This cascade initiates from AuNPs-induced intracellular ROS elevation, confirmed by flow cytometry showing increased cytoplasmic ROS and mitochondrial superoxide production (76). AuNPs generate ROS partly through intrinsic catalytic activity, converting H2O2 into H2O and O2 while enhancing catalase activity to modify the tumor microenvironment via hypoxia alleviation and immune potentiation (77). Additionally, AuNPs elevate superoxide dismutase (SOD) activity, causing H2O2 accumulation that activates caspase-dependent signaling pathways to induce cancer cell apoptosis (77). AuNPs’ cytotoxicity against cervical cancer cells depends critically on nanoparticle diameter and subcellular localization (78). Dae et al. found extracellular monodisperse AuNPs prolong HeLa cell mitosis without inducing apoptosis by forming division-disrupting nano-barriers. By contrast, 111nm extracellular AuNPs trigger ROS-mediated cell death with cytokinesis arrest, while 83nm particles cause transient M-phase delay followed by normal cytokinesis and G1-phase entry (78).

2.2.3 High-efficiency photothermal tumor ablation utilizing AuNPs

AuNPs act as efficient photothermal transducers, enabling precise tumor ablation under targeted guidance (21). Recent refinements include S-nitrosothiol-modified AuNPs releasing nitric oxide during PTT to simultaneously soften tumor extracellular matrix and generate mitochondrial reactive nitrogen species for enhanced cytotoxicity (79). Multibranched gold nanocrystals further outperform spherical or rod-shaped counterparts in photothermal conversion efficiency, confirming morphology as critical design parameter (21). PDT employs photosensitizers to generate cytotoxic ROS but faces limitations including toxicity and poor cellular uptake. Armin and team further demonstrated that AuNPs functionalized with protoporphyrin IX and FA via mercaptohexanol linkers enhance both cancer selectivity and cytotoxic efficiency (80).

2.2.4 Radiosensitization effects of AuNPs in radiotherapy

AuNPs enhance cervical cancer radiotherapy efficacy through their high atomic number (Z = 79), which dramatically exceeds biological elements. This promotes X-ray/γ-ray absorption, generating amplified secondary electron fluxes that directly damage tumor DNA (81). Radiation-activated gold nanorods (AuNPs, 54.6 ± 7.11nm, spherical) further catalyze water decomposition, producing cytotoxic ROS (82). Functionalized variants concentrate radiation energy within lesions. Radiosensitization varies significantly with geometry: AuNRs surpass spheres (83). Nanocubes deposit 18.5% (18 MV) to 23.1% (6 MV) higher electron doses than nanospheres within 1.1 µm radii, achieving maximum dose enhancement at 6 MV (84).

3 AuNPs in ovarian cancer

3.1 Diagnosis

3.1.1 Colorimetric detection utilizing AuNPs

Colorimetry enables rapid ovarian cancer biomarker screening but suffers from limited resolution. Eda et al. circumvented this via smartphone-integrated analysis leveraging mobile imaging hardware advances (~40nm) (85). Alternatively, Hao et al. engineered Mg/Fe-layered double hydroxide nanoflowers as high-density AuNPs (~10nm, Rapid injection synthesis) carriers for lateral flow immunoassay (LFIA) (86). These porous templates achieve ultrahigh AuNPs loading, lowering HE4 detection to 50 pM (86).

3.1.2 AuNPs-engineered electrochemical biosensors

CA125 is the clinical gold standard for ovarian cancer serology. Current AuNP-based detection platforms vary primarily in electrode composition and surface modification strategies(Table 5), integrating AuNPs with carbon nanomaterials (graphene, CNTs), polymers (chitosan, polydopamine, PAMAM), or novel frameworks (MXenes, MOFs) to enhance nanoparticle density, antigen capture efficiency, and electron transfer kinetics. The integration of MOFs with AuNPs achieves reproducible CA12-specific recognition, demonstrating a RSD of 2.98% in repeatability experiments (87). Zahra’s MXene/GQD/AuNPs composite achieves a record LOD of 0.075nU/mL (88). DLS sensors offer the broadest linear range (5fg/mL~50ng/mL) for high-dynamic CA125 quantification (89), while AuNP-DNA fluorescence quenching enables continuous biomarker monitoring. Near-field communication (NFC) integration further streamlines data acquisition, enhancing clinical utility (90).

Table 5

No Particle size Surface functionalization of AuNPs Highlights of Study Clinical sample LOD Linear range Reference
1 Cu single-atom/AuNPs modified electrode Artificial serum 0.37 pg/mL;1.58 pg/mL 0.005~500 ng/mL (91)
2 ~14nm Thiolation; Covalent bonding PAMAM/AuNPs and 3D rGO-MWCNTs modified electrode;Succinic anhydride-modified chitosan Artificial serum 6 μU/mL 0.0005~75 U/mL (92)
3 ~15nm Thiolation In-situ grown AuNPs/GaN Schottky junction via H2O2 etching;AuNPs size-controlled Fermi level/charge transfer efficiency Serum(4) 0.3 U/ml 1~100 U/mL (93)
4 ~13nm Target-aptamer binding modulated AuNPs aggregation for fluorescence on/off; Serum(4) 0.015 U/mL;7.5 pg/mL 0.01~2.0 U/mL;0.01~0.9 ng/mL (94)
5 ~13nm Thiolation Dual-signal detection: DLS particle size and fluorescence; Serum(2) 1.1 fg/mL 5 fg/mL~50 ng/mL (89)
6 Thiolation; Covalent bonding Microporous carbon modified SPCE;Smartphone-based NFC signal acquisition; Serum(6) 0.4 U/mL 0.5~50.0 U/mL (90)
7 ~4.5nm TDN-enhanced TMSD with AuNPs/Ru/ZIF-MOF signal probes; Serum(4) 0.006 pg/mL 0.01 pg/mL~10 ng/mL (95)
8 122 ± 11nm Thiolation AuNPs modified FTO electrode;Oligonucleotide recognition elements (antibody-free); Serum(3) 2.6 U/mL 10~800 U/mL (96)
9 MXene-GQD/AuNPs modified electrode Artificial serum 0.075 nU/mL 0.1 μU/mL~1 U/mL (88)
10 Thiolation; Covalent bonding AuNPs/RGO/PTH-modified DSPCE electrode Artificial serum 0.069 pg/mL; 0.058 pg/mL 1~100 pg/mL (97)
11 ~70nm AuNPs and DES-synthesized PTB co-modified SPCE Artificial serum 1.20 pg/mL 5~100 pg/mL (98)
12 Electrodes modified with MOF@AuNPs-based nanocomposites Serum 7.185nU/mL 10~70nU/mL (87)
13 Thiolation; Electrostatic adsorption Two biocompatible 2D COFs (EP-TD-COF and AuNPs@COFBTT-DGMH) effectively preserved antibody activity and provided a favorable microenvironment, synergistically enhancing the stability and sensitivity of the immunosensor Artificial serum 0.089mU/mL 0.00027~100U/mL (99)
14 ~54.61nm The hybrid nanostructure of α-MnO2 nanorods and AuNPs enhanced conductivity and sensitivity Serum 9.82ng/mL 10~70ng/mL (100)
15 CuCo-ONSs@AuNPs nanocomposite-modified electrode Serum(6) 39nU/mL 0.1μU/mL~1mU/mL (101)
16 Thiolation A biosensor capable of simultaneously interacting with sEV and CDDP was developed, enabling the simultaneous quantification of sEV and CDDP using SERS, thereby overcoming the heterogeneity and protein interference issues in SERS analysis of sEV Positive serum(99); negative serum(20) (102)

Sensor design scheme for detecting CA125 based on AuNPs.

Beyond CA125, AuNP-based sensors target biomarkers including p53, HE4, exosomes, and DNA methylation (91, 103106). Following Weiwei et al.’ s MOF-AuNPs for CA125 (95), Xu and team developed a sandwich electrochemical immunosensor using synergistic signal amplification between Prussian blue (PB) and thiolated ionic MOF composites (TIMO+F-KB@AuNPs) for HE4 quantification (107). The platform employs TIMO+F-KB@AuNPs as conductive sensing substrates for capture antibody (Ab1) immobilization, while PB nanoparticles carry detection antibodies (Ab2). HE4 binding forms an Ab1-HE4-Ab2-PB complex, generating electrochemical signals proportional to concentration (linear range: 0.1~80ng/mL, LOD: 0.02ng/mL) (107). Demonstrating high selectivity, reproducibility, and stability with 97.10~114.07% serum recovery, it enables early ovarian cancer diagnosis (Figure 8). Separately, superparamagnetic CoFeB enhances AuNPs-based p53 detection (LOD: 0.006 U/mL) (104). Furthermore, exosomes predict ovarian cancer chemotherapy response. Meshach and team developed a cysteine-functionalized AuNP (Au-cys) biosensor using SERS to simultaneously capture cisplatin and small extracellular vesicles from biological samples, enabling concurrent early detection and treatment efficacy assessment (102).

Figure 8

Diagram illustrating a biosensor fabrication process. TiMOF-KB is combined with AuNP to form TiMOF-KB@AuNP, which is applied on GCE with antibodies, PEG, and HE4. Separately, citric acid, FeCl3, and K4[Fe(CN)6] are stirred at sixty degrees Celsius to create PB NP, forming a PB-Probe when combined with Ab2. The final configuration on GCE shows interlinked components, leading to a graph demonstrating an electrochemical response with current (I/μA) versus potential (E/V).

Shows the principle of the prepared electrochemical biosensor for fast detection of HE4 (107). (Copyright permission obtained).

AuNPs facilitate ovarian cancer diagnosis via urine, exhaled gas, and cyst fluid analysis (108, 109). Thomas and team pioneered nanopore sensing where AuNPs capture 13 cysteine-containing urinary peptides within α-hemolysin nanopores, generating distinct current signatures: stepwise reductions for small peptides versus polymorphic fluctuations for larger ones, enabling prolonged single-molecule characterization (108). AuNPs-based platforms also detect microbiome-derived Volatile organic compounds (VOCs) in exhaled breath with 82% screening accuracy (110).

3.1.3 AuNPs-enabled innovative imaging strategies

AuNPs drive transformative ovarian cancer imaging advances (19). Dheeraj and team engineered FA-targeted, hydrazinonicotinamide-chelated AuNPs enabling efficient 99mTc radiolabeling for tumor-specific single-photon emission computed tomography (SPECT) contrast (111). Further functionalization yielded GO/SPIO/AuNP composite sheets integrating PTT, radiotherapy, and MRI within a unified theranostic platform (112).

MARS spectral photon-counting CT (SPCCT), though primarily preclinical, enables material-specific imaging via energy-dependent X-ray attenuation. Dhiraj et al. functionalized AuNPs with LHRH via PEG tethers for ovarian cancer targeting (113). Intraperitoneal administration in murine models achieved selective accumulation in peritoneal tumors (0.46~2.12ng/mg, ICP-MS). While current SPCCT sensitivity limited absolute quantification, it mapped gold distribution patterns (113). Increased LHRH density (3000~15000molecules/particle) enhanced targeting while maintaining >60% metabolic activity at therapeutic concentrations (12~30μg/mL), establishing a novel theranostic strategy (113).

Functionalized AuNPs support ovarian cancer-specific detection via fluorescence lifetime imaging (114), dark-field (115), and confocal Raman microscopy (116). SERS imaging further enables chemoresistance prediction and survival outcome assessment (117).

3.2 Treatment

3.2 .1. AuNPs-based drug delivery systems

AuNPs enable targeted ovarian cancer drug delivery, enhancing dispersion or internalization of agents like linalool, cetuximab, paclitaxel, let-7a miRNA, and nidocarcinoma-derived factor(Table 6). DOX-AuNPs show superior tumor growth inhibition versus free doxorubicin while overcoming payload leakage limitations (118). Engineered for MICU1-targeting siRNA delivery, they achieve >85% silencing efficiency via lysosome evasion, addressing key shortcomings of conventional carriers (119).

Table 6

No Particle size Surface functionalization of AuNPs Drug Highlights of Study Animal model Toxic Reference
1 ~10nm Covalent bonding DTX Plasmonic photothermal therapy (PPTT) enables pH-triggered controlled release of docetaxel by disrupting halloysite nanotube (HNT) interlayer hydrogen bonds via Au nanoparticle-mediated photothermal effects The MTT results indicate low toxicity in 3T3 (115)
2 ~13nm Thiolation; Covalent bonding CALNN;Linalool GSH-capped linalool delivery; CALNN peptide conjugation; Caspase-8/p53 activation & NF-κB inhibition Considered (120)
3 ~40nm Thiolation NDC - 1;NDC - 2 Thiol-Au conjugated naproxen derivatives; Simple high-loading platform; 5× lower IC50 vs free drugs Considered (121)
4 ~13nm Thiolation DOX DNA-hybridized Dox loading; pH-responsive release; 2.5× greater in vivo suppression vs free Dox BALB/c nude mice Considered (118)
5 ~20nm auroliposome AuNP-embedded siRNA liposomes; Caveolae-mediated uptake enhancement; PDX model efficacy No toxicity (119)
6 12 ± 2 nm Thiolation miR - 145 FSH receptor-targeted delivery via FSH33 peptide Considered (122)
7 ~30nm Electrostatic adsorption; Covalent bonding; Thiolation PTX Multimodal imaging (PA/FL/CT); pH-responsive PTX release; Photothermal-enhanced delivery mice Considered (123)
8 ~10nm DTX HNT/AuNP/SORT antibody integration; PPTT/pH-triggered release (44 °C activation); Selective cancer killing The MTT results indicate low toxicity in 3T3 (115)
9 10~15nm TXT Ca(OH)2 tumor-penetration pretreatment; Magnetic/PPTT/CT multifunctional system; 89% growth inhibition mice The MTT results indicate low toxicity in 3T3 (28)
10 60 ± 5nm*30 ± 3nm Thiolation; Covalent bonding CSA-131 Peanut-shaped AuNP delivery of ceragenin; Systemic administration potential BALB/c nude mice No toxicity (124)
11 ~19nm Thiolation; Covalent bonding TfQ Theaflavin-mediated synthesis/stabilization; Low hemolytic nanocomposite No toxicity (125)
12 ~10nm Thiolation TZ; miR-200c First integration of miR-200c with AuNPs-TZ nanocomplexes demonstrated. Considered (126)
13 ~20nm Thiolation DOX QbD-guided functionalization yielded pH/NIR-responsive AuNPs-L-Dox nanoplatform for selective tumor drug release with reduced systemic toxicity Low toxicity s(127)

Design of AuNPs for the treatment of ovarian cancer (drug delivery).

Antibody or peptide-conjugated AuNPs enable precise ovarian cancer targeting (128). Edison and team engineered FSH33-AuNPs covalently conjugated to tumor-suppressive miR-145 (122). This system protects miR-145 from degradation, mediates selective cancer cell internalization, and inhibits proliferation, migration, anchorage-independent growth, and VEGF secretion. AuNPs enable co-delivery of multiple therapeutic agents, as demonstrated by Tommaso et al. who engineered miR-200c and trastuzumab (TZ)-loaded nanoparticles that dual-target critical pathways driving SKOV3 cell survival and proliferation in vitro, overcoming TZ resistance while potentially improving therapeutic outcomes for HER2-positive ovarian cancer (126). Beyond antibody/peptide targeting, TME and hyperthermia trigger drug release from AuNPs,123. Reza et al. engineered antibody-conjugated magneto-gold composites (TXT@Fe3O4/PVA/Au-SORT) for ovarian cancer (28). Photothermal AuNPs heating dissociates the PVA matrix, achieving precise TXT release (94.4 ± 4.1% over 180 min in TME). Ca(OH)2 pretreatment combined with TXT therapy enhanced intratumoral accumulation, inhibited migration, and induced DNA damage, achieving 78.3% tumor suppression with reduced systemic toxicity (Figure 9).

Figure 9

Fluorescence microscopy images comparing fibroblast (3T3) and cancerous cells (ATCC HTB76) stained with different treatments: Cargo-SORT, Cargo-SORT Pretreated, Cargo, and Individual TXT. The images show three rows labeled as Stained cell, TXT, and Merge, displaying blue, green, and red fluorescence. Each column represents a different treatment method, showing cellular interactions and distribution. Scale bars indicate 50 micrometers.

Confocal images of the subjected TXT@Fe3O4/PVA/Au nano-therapeutic to the stained cells. Green: HTB76 cancerous, and blue: NIH 3T3 fibroblast cells (106 DFU), in the presence of the individual TXT, TXT@Fe3O4/PVA/Au (Cargo), and TXT@Fe3O4/PVA/Au-SORT particles (Cargo-SORT) particles. Cell staining was performed using crystal violet, and incubation was carried out at 37 °C with 95% humidity for 2 hours. Pretreatment was done with Ca(OH)2@Fe3O4/PVA/Au-SORT particles in the same dosage with the TXT-containing therapeutic (10μg/mL) (28).

Notably, AuNPs morphology critically influences therapeutic outcomes: anisotropic AuNPs@CSA-131 exhibit enhanced cytotoxicity against ovarian carcinoma versus spherical counterparts (124). Furthermore, AuNPs modulate drug presentation in vivo, facilitating theaflavin oxidation to cytotoxic quinone derivatives (125). Regarding therapeutic side effects, The triple-modality approach (ultrasound/AuNCs/cisplatin) overcomes cisplatin resistance in resistant ovarian cancer models, suggesting reduced chemotherapy side effects with translational potential (129).

3.2.2 Intrinsic antitumor effects of AuNPs

AuNPs inhibit ovarian carcinoma invasiveness by targeting key oncogenic pathways: impeding MAPK signaling, suppressing EMT-associated proteins, and disrupting the IGFBP2/mTOR/PTEN autoregulatory axis, downregulating IGFBP2, suppressing PI3K/AKT/mTOR activation, and reactivating PTEN (130, 131). Current understanding posits that AuNPs disrupt multicellular TME communication (cancer cells, cancer-associated fibroblasts, endothelial cells), downregulating pro-tumorigenic cytokines and growth factors (132, 133). Specifically, they reduce CC-secreted fibroblast-activating proteins (TGF-β1, PDGF, uPA, TSP1) and inhibit tumor angiogenesis by blocking VEGF-VEGFR2 signalling (133, 134). This positions AuNPs as key tools for elucidating and disrupting pro-tumorigenic crosstalk. AuNPs synchronize disulfidptosis and ferroptosis in ovarian cancer by modulating the SLC7A11/GSH/GPX4 axis (135). The composite system exploits AuNPs’ glucose oxidase-like activity and Ap-mediated GLUT1 downregulation to induce metabolic crisis (135). Glucose deprivation limits NADPH replenishment, disrupting cystine/cysteine conversion and resolving the disulfidptosis-ferroptosis execution paradox. Concurrently, iron-based components deliver Fe²+ while AuNPs-catalyzed glucose oxidation self-supplies H2O2, amplifying Fenton reactions and ferroptotic death (135).

Beyond influencing signalling pathways, AuNPs enhance nuclear rigidity via perinuclear laminA/C overexpression, impeding cancer cell migration (136). Concurrently, they induce ROS-mediated apoptosis/autophagy, trapping cells in G0/G1 phase (137). Anisotropic AuNPs exert enhanced anti-migratory effects versus spherical counterparts (138). Analogous to cervical cancer applications, morphological engineering of AuNPs enhances their cytotoxic efficacy against ovarian cancer cells. Irfan et al. attribute this phenomenon to elongated-branched antibody-functionalized AuNPs effectively evading serum protein corona entrapment, thereby facilitating optimal aptamer binding to HER2 receptors on cancer cell surfaces (139). This mechanism induces significant cytotoxicity in HER2-overexpressing SKOV3 cells through targeted apoptosis initiation.

3.2.3 High-efficiency photothermal tumor ablation utilizing AuNPs

AuNPs enable synergistic chemo-photothermal therapy for ovarian cancer (127, 140). Yiting et al. engineered a genetically fused HSA nanocarrier (RHMH18@AuD) self-assembling via histidine hydrophobicity to encapsulate DTX while forming ultrasmall AuNPs through biomimetic mineralization (141). This 80-nm platform prevents HSA denaturation and reduces inorganic nanoparticle toxicity. MMP-2 cleavage at tumors releases RGD-HSA@Au (mediating photothermia) and His@DTX micelles, with acidic TME-triggered DTX release. The system demonstrated targeted cellular uptake, significant tumor suppression, and 100% survival at 70 days versus complete mortality in monotherapy groups by day 62, establishing a high-efficacy, low-toxicity therapeutic strategy.

Diverse AuNPs composites serve as photothermal agents for ovarian cancer PTT. rGO-AuNPs-PEG exhibits strong SERS signals, NIR-II PA signals, and high photothermal efficiency in tumours under 1061 nm laser irradiation (142). Similarly, silica nanocapsules containing aggregated AuNPs yolk-shell structures (aAuYS) demonstrate enhanced photothermal effects with 808 nm laser exposure (143). Curcumin-incorporated gold nanoshells (Cur-AuNShs) show efficient photothermal conversion with potential for selective cancer targeting and treatment. Additionally, AuNPs morphology influences PTT efficiency (144). For instance, dumbbell-shaped Au-Fe3O4 elevate thermal conversion efficacy (145).

To overcome resolution limitations in image-guided PTT, Annan et al. developed ultra-small GnRHR-targeted AuNDs (Au-GRHa, 3.2nm) (146). Prepared via electrochemical displacement and ligand conjugation, these nanoconstructs enable dual-modal fluorescence/CT imaging with superior CT contrast (attenuation coefficient: 5.153cm²/g) and renal clearance. GnRHa targeting boosted SKOV3 cellular uptake by 76% versus non-targeted counterparts. Under 808 nm irradiation, localized temperatures reached 50 °C within 5 min, inducing apoptosis via membrane disruption and protein denaturation. In vivo peak tumor accumulation occurred at 2 h, with subsequent PTT significantly suppressing tumor growth without hemolysis or toxicity, establishing a precise image-guided therapeutic platform.

PDT and PTT act synergistically against ovarian cancer. A multifunctional nanomicrogel (Au@MSN–Ter/THPP@CM@GelMA/CAT) demonstrates concurrent photodynamic efficacy (650nm) and photothermal ablation (980nm) (147).

3.2.4 Radiosensitization effects of AuNPs in radiotherapy

AuNPs exhibit radiosensitizing effects, exemplified by thioglucose-bound nanoparticles (Glu-GNPs) enhancing ovarian cancer radiotherapy (148). The GO-SPIO-Au nanoflower platform integrates graphene oxide (NIR-PTT), AuNPs (radiosensitization), and superparamagnetic iron oxide (MRI) for image-guided therapy (112). In murine models, combined PTT/RT yielded 1.85× and 1.44× higher efficacy than PTT or RT alone, respectively. Kinga et al. developed a novel cancer therapy combining antibody-drug conjugates (ADCs) with β-emitting ¹98AuNPs conjugated to trastuzumab emtansine (T-DM1), demonstrating specific HER2 affinity and synergistic efficacy against HER2-overexpressing cancers at low T-DM1 doses (0.015~0.124μg/mL) with 10–20 MBq/mL radiation (149). Continuous 7-day treatment (20 MBq/mL+0.031μg/mL T-DM1) disrupted 3D tumor spheroids, suggesting potential for HER2-positive breast/ovarian cancer treatment despite preferential suitability of inorganic nanoradiopharmaceuticals for localized delivery (Figure 10) (149).

Figure 10

Grid showing microscopic images of samples over time (Day 0, Day 2, Day 3, Day 7) under different treatments. Columns represent varied compounds and activity concentrations, including ^198AuNPs, ^198AuNPs-T-DM1, T-DM1, and controls. Rows depict changes or stability in sample morphology over the specified days.

Microscopic images of the measured control and compound-treated SKOV-3 spheroids (149).

4 Integrated diagnostic and therapeutic platform

AuNPs serve as pivotal components in multimodal theranostic platforms owing to their distinctive physicochemical properties, enabling visualized precision therapy of pathological lesions. Diversified therapeutic strategies demonstrate that targeted accumulation of AuNPs at disease sites generates synergistic effects, with imaging guidance being critical for maximizing diagnostic-therapeutic efficacy. Current research has developed functionalized AuNPs-based visualization approaches for gynecological malignancies. Zhang’s team overcame single-modality imaging limitations by establishing a PAI/CT/MRI multimodal system centered on functionalized AuNPs, effectively addressing the low X-ray attenuation coefficient inherent to inorganic materials (67). At 200 µg/mL, Au-UCNPs-DSPE-PEG precisely delineated cervical cancer location, dimensions and morphological characteristics in murine models, while their photothermal conversion capability simultaneously enabled photoacoustic imaging-guided combination photothermal and photodynamic therapy (67). Beyond physical modalities, AuNPs function as chemotherapeutic carriers. Taheri et al. employed CT to monitor TXT@AuNPs distribution for efficacy assessment, yet single-modality CT proved inadequate for tracking drug release kinetics (28). Wang’s team addressed this through multimodal imaging (PAI/FL/CT) for real-time surveillance of drug-loaded AuNPs. Paclitaxel release induced fluorescence signal fluctuations due to AuNP surface restructuring while accelerating nanoparticle metabolic clearance, consequently reducing photoacoustic intensity in lesions (123). For quantitative release monitoring, Yim’s team innovatively leveraged AuNPs’ low X-ray attenuation property (66). Electrostatic adsorption-triggered aggregation of radioiodinated AuNPs, occurring through opposite surface charges after DOX release, significantly enhanced lesion signals on PET-CT imaging (66). These aggregates maintained prolonged high-signal states due to extended half-life, enabling sustained dynamic observation.

5 Challenges and limitations

Despite being a promising nanomaterial, AuNPs must overcome several significant barriers prior to broad clinical adoption for diagnosing and treating gynecological malignancies.

The safety profile of AuNPs represents a modifiable property, critically dependent on factors such as particle size, synthesis method, exposure route, dosage duration, and the specific biological milieu (150, 151). In numerous studies cited above, AuNPs are often assumed to be chemically inert and stable materials, particularly when PEG-modified, exhibiting negligible toxicity at certain doses. Merely 28 investigations to date have employed MTT assays and related techniques to evaluate the cytotoxicity of novel functionalized AuNPs toward normal cells or animal models. In the clinical context of managing gynecological malignancies, chemotherapy is typically a protracted process (152). Repeated administration of functionalized AuNPs during such long-term treatment carries a significant risk of inducing antibodies against the nanoparticle surface characteristics. This immunogenic response could potentially compromise the targeting efficacy of AuNPs and disrupt normal immune function. Furthermore, diverse AuNPs synthesis and functionalization strategies can leave toxic chemical residues on the particle surfaces. These modifications also alter the chemical properties and size of the AuNPs, potentially hindering renal clearance and leading to progressive bioaccumulation. Additionally, compared to free drugs, administering chemotherapeutic nanoparticles during ovulation increases ovarian toxicity and reduces fertility (153). Therefore, the menstrual cycle warrants consideration in the design and implementation of AuNPs therapies for female patients. These concerns underscore the necessity for further comprehensive evaluation of AuNPs systemic safety in humans and detailed investigation into nanoparticle pharmacokinetics to fully assess their absorption, distribution, metabolism, and excretion processes.

Addressing AuNP safety challenges requires systematic pharmacokinetic studies (absorption, distribution, metabolism, excretion) in animal models to define critical thresholds for nanoparticle-induced irreversible organ damage, enabling establishment of dimensionally-, morphologically-, and synthesis-method-dependent safety dosage windows across varied administration regimens. Green synthesis strategies utilizing novel catalysts demonstrate promising toxicological safety profiles, potentially representing key advancement pathways (75, 76). Multifunctional AuNPs may shorten chemotherapy cycles while combined PTT and PDT therapies could circumvent antibody responses from chronic treatment (127, 141). Nevertheless, large-scale animal validation remains indispensable; current maximum reported cohort sizes of 28 subjects prove insufficient, particularly given physiological disparities between rodent and human systems, necessitating expansion to rabbit and non-human primate models. These imperatives collectively emphasize comprehensive assessment of systemic AuNP safety in humans and rigorous pharmacokinetic investigation.

The diagnostic and therapeutic efficacy of AuNPs requires further validation. The majority of studies demonstrating potential benefits are confined to cell lines or small animal models, overlooking the substantial complexity of human physiology. In cervical cancer diagnostics, merely 15 of 34 peer-reviewed investigations disclosed clinical sample accuracy (n=9) or spiked serum analyte recovery (n=6), with two HPV detection reports achieving >95% accuracy in cohorts exceeding 100 specimens. Regarding therapeutic applications, only 2 of 15 cervical cancer publications documented AuNP efficacy in murine models. Similarly, among 28 ovarian cancer diagnostic analyses, 18 provided clinical validation data (n=4) or serum recovery metrics (n=14), though clinical specimens numbered ≤10 per analysis. Whereas 21 of 28 therapeutic investigations asserted significant antitumor outcomes, merely 9 confirmed efficacy in animal models with quantification parameters undisclosed. Humans are continuously exposed throughout life to diverse natural and anthropogenic nanoparticles. Such environmental nanoparticle contamination constitutes a significant exogenous interference factor, potentially impeding the function of administered AuNPs. For instance, titanium or iron oxide nanoparticles can inhibit cancer cell uptake of AuNPs (154). Beyond these exogenous factors, endogenous human variables also critically influence AuNPs performance. Evidence indicates that elevated cholesterol levels and specific lipid ratios disrupt the delivery capacity of DOX-AuNPs systems (155). Even in Phase III clinical trials, AuNPs-based drug delivery systems demonstrated suboptimal recognition efficiency for ovarian cancer, with the majority of intratumoral nanoparticles becoming either trapped within the extracellular matrix or sequestered by perivascular tumor-associated macrophages (156). Compounding these issues, many studies report human validation based on single-digit sample cohorts, lacking comparison with healthy individuals or non-gynecological cancer patients, and frequently omit detailed accuracy data (Supplementary Material 1).

Subsequent investigations must validate AuNPs’ true diagnostic-therapeutic efficacy through large-scale animal models and clinical trials, with priority assessment of their resistance to complex biological interferences including protein corona formation and lipid adsorption. Although functionalized AuNPs demonstrate anti-interference capabilities in select studies, the disparity between simulated laboratory conditions and physiological environments necessitates rigorous in vivo verification. Novel non-spherical geometries such as high-aspect-ratio nanostars effectively circumvent protein corona shielding while enhancing tumor targeting precision (139). Notably, nanoparticles within the 10~20 nm size range exhibit optimal performance, yet synthesis-dependent variations in AuNP dimensions/morphologies demand standardized evaluation frameworks to enable cross-study comparability and collaborative advancement. Furthermore, addressing prevalent data limitations stemming from insufficient clinical samples requires establishing multicenter validation frameworks. AuNPs’ therapeutic potential should transcend conventional drug delivery roles toward multimodal theranostic platforms, exemplified by triple-modality regimens integrating PTT, controlled chemotherapeutic release, and radiosensitization, with concurrent treatment monitoring via PAI and PET-CT. While four diagnostic investigations have incorporated machine learning for enhanced SERS-based high-throughput chip detection, deep learning applications in medical image interpretation remain unexplored. Integrating big data analytics with mobile health technologies could establish intelligent diagnostic networks to reduce misinterpretation risks.

Finally, the cost implications of AuNPs systems demand serious consideration. In resource-limited developing nations, economic constraints remain pivotal in restricting large-scale disease screening initiatives. Most current studies fail to address the cost structure of AuNPs-based diagnostic platforms, with only a handful reporting screening expenses or reusability metrics (157). A predominant focus on novel materials and intricate architectures, particularly acute within the domain of AuNPs-designed electrochemical sensors, often overshadows the underlying premise of screening: low cost and high accessibility. Furthermore, AuNPs synthesis methodologies themselves represent significant cost determinants, compounded by concerns regarding environmental impact and suboptimal production efficiency (151). These factors establish cost as a paramount consideration for the clinical translation of AuNPs technologies.

The convergence of artificial intelligence and low-cost smartphones offers a significant pathway to reduce expenditures associated with AuNP-based diagnostic systems, effectively lowering human resource requirements, time costs, and sample transport losses. Implementing a three-tier diagnostic network comprising colorimetric detection units, subject mobile client devices, and hospital data centres substantially enhances population screening efficiency. A core advantage of this system lies in the capacity for AI algorithms to perform localized processing directly on smartphones, enabling preliminary screening and interpretation of test results; only data indicating anomalies require transmission to the hospital data centre for verification, thereby markedly alleviating the healthcare burden in resource-limited settings. This tiered network fundamentally transforms the traditional hierarchical “hospital-centric–healthcare worker–subject” information delivery model. By empowering subjects with autonomous testing capabilities, it shifts the paradigm from passive information reception to proactive health management, significantly improving participant engagement and adherence. From a technological development perspective, research efforts should recalibrate their focus regarding AuNPs: prioritizing material design optimization that establishes an optimal cost-accuracy balance over the pursuit of increasingly complex material combinations; directing energy towards developing scalable, low-power manufacturing processes; and advancing clinical integration through modular designs that reduce the overall system cost.

Notably, clinical trials of AuNPs in gynaecological malignancies remain limited. However, recent human studies across non-gynaecological cancers, spanning breast cancer, colorectal carcinoma and cutaneous disorders, demonstrate expanding clinical evaluation (158162). These advances confirm that current implementation challenges are addressable and reveal diagnostic and therapeutic benefits warranting further translation in gynaecological oncology. Collectively, AuNPs systems exhibit significant potential for enhancing diagnostic accuracy, improving patient quality of life, and optimizing clinical prognoses. Looking forward, their unique physicochemical properties position AuNPs as transformative agents in next-generation gynecologic oncology, enabling minimally invasive theranostics, real-time disease monitoring, and personalized treatment regimens. Continued advancements in nanomaterial engineering, refined targeting methodologies, comprehensive safety evaluations, and integration of AI further solidify AuNPs platforms to assume an increasingly critical and expansive role in future integrated theranostic frameworks (Figure 11).

Figure 11

Flowchart illustrating the use of gold nanoparticles (AuNPs) from synthesis to future applications in 2025. Diagnoses strategies include colorimetric detection, electrochemical biosensors, SERS detection, and innovative imaging. Treatment strategies involve drug delivery, antitumor effects, photothermal tumor ablation, and radiosensitization in radiotherapy. Challenges highlighted are biosafety, diagnostic efficacy, and cost-effectiveness. Countermeasures recommend thorough validation, AI integration, and standardized frameworks. Graphical representations of color scales, imaging equipment, and lab icons support each point.

Current diagnostic and therapeutic approaches utilizing AuNPs in cervical and ovarian cancers, and associated challenges and future prospects.

6 Conclusion

Clinical management of gynecological malignancies faces significant challenges, including difficulties in early detection, high therapeutic resistance, substantial risks of residual disease post-surgery, and considerable toxicity from conventional radiotherapy and chemotherapy. These critical limitations demand innovative technological solutions for precision diagnostics and therapeutics. Recent advances in nanotechnology provide transformative momentum for gynecologic oncology, with AuNPs offering particularly promising strategies due to their tunable dimensions, morphological versatility, customizable surface functionalization, and unique optical properties. AuNPs serve as highly sensitive contrast agents that enhance detection rates for early-stage lesions and micrometastases. Functionalization with antibodies, peptides, or aptamers enables precise targeting of therapeutic payloads to disease sites and facilitates ultrasensitive detection of trace biomarkers in liquid biopsies. Furthermore, their exceptional photothermal conversion efficiency and photochemical capabilities permit concurrent targeted chemotherapy with spatially precise photothermal and photodynamic therapy at tumor sites. This integrated theranostic approach positions AuNPs-based systems to drive a paradigm shift from isolated interventions toward closed-loop precision management in gynecologic oncology. Nevertheless, further validation remains imperative to address clinical translation barriers and long-term safety profiles.

Statements

Author contributions

SZ: Data curation, Formal Analysis, Methodology, Software, Writing – original draft. TL: Data curation, Writing – original draft. DJ: Data curation, Formal Analysis, Methodology, Writing – original draft. HS: Data curation, Formal Analysis, Writing – review & editing. HH: Supervision, Writing – review & editing. ZF: Funding acquisition, Resources, Writing – review & editing. XS: Writing – review & editing.

Funding

The author(s) declare financial support was received for the research and/or publication of this article. This study was financially supported by the National Natural Science Foundation of China (NO.82173327, NO.82272916).

Acknowledgments

We also thank Biorender for the templates used in the graphical abstract and Figure 11.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Generative AI statement

The author(s) declare that no Generative AI was used in the creation of this manuscript.

Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fonc.2025.1664340/full#supplementary-material

Glossary

  • FDA

    US Food and Drug Administration

  • PEG

    Polyethylene glycol

  • OCT

    Optical coherence tomography

  • VIA

    Visual inspection with acetic acid

  • LOD

    Limit of detection

  • LFA

    Lateral flow assay

  • PDA

    Polydopamine

  • PEBA

    Photoelectrochemical biochip array

  • MLNPs

    Multilayered nanoparticles

  • WS2

    Tungsten disulfide

  • MoS2

    Molybdenum disulfide

  • ND

    Neutral density filter

  • 4-MBA

    4-Mercaptobenzoic acid

  • DTNB

    5,5′-Dithiobis-(2-nitrobenzoic acid)

  • 4,4′-DP

    4,4′-Dipyridyl

  • RGD

    Arginylglycylaspartic acid peptide

  • NLS

    Nuclear localization signal

  • TAP

    Tris(2-aminophenol)

  • PHEN

    1,10-Phenanthroline

  • 3-MPA

    3-Mercaptopropionic acid

  • TLR7/8

    Toll-like receptors 7/8

  • MPA

    3-Mercaptopropionic acid

  • MPS

    3-Mercaptopropyltrimethoxysilane

  • PVP

    Polyvinylpyrrolidone

  • ECM

    Extracellular matrix

  • RNS

    Reactive nitrogen species

  • MB

    Methylene blue

  • Pp-IX

    Protoporphyrin IX

  • AuNRs

    Gold nanorods

  • DEF

    Dose enhancement factor

  • FFPE

    Formalin-fixed paraffin-embedded

  • AGR2

    Anterior gradient 2

  • Mg/Fe LDH

    Mg/Fe-layered double hydroxide

  • PAMAM

    Polyamidoamine

  • MXene

    Transition metal carbide/nitride

  • MOF

    Metal-organic framework

  • GQD

    Graphene quantum dot

  • DLS

    Dynamic light scattering

  • TIMO+F-KB@AuNPs

    Thiolated Ionic Metal-Organic Framework-KB@AuNPs

  • PB

    Prussian blue

  • CoFeB

    Cobalt iron boride

  • CDDP

    Cisplatin

  • sEV

    Small extracellular vesicles

  • VOCs

    Volatile organic compounds

  • HYNIC

    Hydrazinonicotinamide

  • GO/SPIO/AuNP

    Graphene oxide/superparamagnetic iron oxide/gold nanoparticle

  • ICP-MS

    Inductively coupled plasma mass spectrometry

  • FLIM

    Fluorescence lifetime imaging microscopy

  • SCRM

    Scanning confocal Raman microscopy

  • FSH33

    Follicle-stimulating hormone peptide fragment

  • VEGF

    Vascular endothelial growth factor

  • PVA

    Poly

  • AuNCs

    Gold nanoclusters

  • PDGF

    Platelet-Derived Growth Factor

  • uPA

    Urokinase-Type Plasminogen Activator

  • TSP1

    Thrombospondin-1

  • Fe-Ap

    Iron-Apigenin

  • AuNSs

    Gold nanostructures

  • HSA

    Human Serum Albumin

  • MMP-2

    Matrix Metalloproteinase-2

  • rGO

    Reduced Graphene Oxide

  • aAuYS

    Aggregated Gold Yolk-Shell

  • Cur-AuNShs

    Curcumin-Incorporated Gold Nanoshells

  • GnRHR

    Gonadotropin-releasing Hormone Receptor

  • AuNDs

    Gold nanodots

  • EDC

    1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide

  • NHS

    N-Hydroxysuccinimide

  • Au@MSN

    Gold-coated Mesoporous Silica Nanoparticles

  • Ter

    Terthiophene

  • THPP

    Tetrakis(4-hydroxyphenyl)porphyrin

  • GelMA

    Gelatin Methacryloyl

  • sNPS

    Single-Nanoparticle Sensing System

  • MutS

    DNA Mismatch Repair Protein

  • EpCAM

    Epithelial cell adhesion molecule

  • COF

    Covalent Organic Framework

  • Apt

    Aptamer

  • LDI-MS

    Laser Desorption/Ionization Mass Spectrometry

  • EMS

    Endometriosis

  • EphB4

    Ephrin type-B receptor 4

  • IDEs

    Interdigitated electrodes

  • CDI

    1,1′-Carbonyldiimidazole

  • MWCNT

    Multi-walled carbon nanotubes

  • APTES

    3-Aminopropyl)triethoxysilane

  • SA-HRP

    Streptavidin-Horseradish Peroxidase

  • GCE

    Glassy carbon electrode

  • ZnO NRs

    Zinc Oxide Nanorods

  • ERGO

    Electrochemically Reduced Graphene Oxide

  • SPCE

    Screen-Printed Carbon Electrode

  • FTO

    Fluorine-Doped Tin Oxide

  • TDN

    Tetrahedral DNA Nanostructure

  • TMSD

    Toehold-Mediated Strand Displacement

  • ZIF

    Zeolitic Imidazolate Framework

  • PTH/PTB

    Polythiophene

  • DSPCE

    Double-Screen Printed Carbon Electrode

  • DES

    Deep Eutectic Solvent

  • CuCo-ONSs

    Copper-Cobalt Oxide Nanosheets

References

  • 1

    Mahmoodi P Fani M Rezayi M Avan A Pasdar Z Karimi E . Early detection of cervical cancer based on high-risk HPV DNA-based genosensors: A systematic review. Biofactors. (2019) 45:101–17. doi: 10.1002/biof.1465

  • 2

    Zarocostas J . Renewed calls to scale-up cervical cancer screening. Lancet. (2024) 403:797. doi: 10.1016/S0140-6736(24)00408-2

  • 3

    Lycke KD Kahlert J Petersen LK Damgaard RK Cheung LC Gravitt PE . Untreated cervical intraepithelial neoplasia grade 2 and subsequent risk of cervical cancer: population based cohort study. BMJ. (2023) 383:e075925. doi: 10.1136/bmj-2023-075925

  • 4

    Cremer M Alfaro K Masch R . Cervical cancer screening in low- and middle-income countries. JAMA. (2021) 325:790. doi: 10.1001/jama.2020.25214

  • 5

    Menon U Gentry-Maharaj A Burnell M Singh N Ryan A Karpinskyj C . Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet. (2021) 397:2182–93. doi: 10.1016/S0140-6736(21)00731-5

  • 6

    Armstrong DK Alvarez RD Backes FJ Bakkum-Gamez JN Barroilhet L Behbakht K . NCCN guidelines® Insights: ovarian cancer, version 3.2022. J Natl Compr Canc Netw. (2022) 20:972–80. doi: 10.6004/jnccn.2022.0047

  • 7

    Konstantinopoulos PA Matulonis UA . Clinical and translational advances in ovarian cancer therapy. Nat Cancer. (2023) 4:1239–57. doi: 10.1038/s43018-023-00617-9

  • 8

    Xu M Cao C Wu P Huang X Ma D . Advances in cervical cancer: current insights and future directions. Cancer Commun (Lond). (2025) 45:77109. doi: 10.1002/cac2.12629

  • 9

    Dai W Zhou J Chen T . Unraveling the extracellular vesicle network: insights into ovarian cancer metastasis and chemoresistance. Mol Cancer. (2024) 23:201. doi: 10.1186/s12943-024-02103-x

  • 10

    Zhou Y Yuan J Xu K Li S Liu Y . Nanotechnology reprogramming metabolism for enhanced tumor immunotherapy. ACS Nano. (2024) 18:1846–64. doi: 10.1021/acsnano.3c11260

  • 11

    Jokerst JV Cole AJ Van de Sompel D Gambhir SS . Gold nanorods for ovarian cancer detection with photoacoustic imaging and resection guidance via Raman imaging in living mice. ACS Nano. (2012) 6:10366–77. doi: 10.1021/nn304347g

  • 12

    Hyun H Sun B Yazdimamaghani M Wielgus A Wang Y Montgomery SA . Tumor-specific surface marker-independent targeting of tumors through nanotechnology and bioorthogonal glycochemistry. J Clin Invest. (2025) 135:e184964. doi: 10.1172/JCI184964

  • 13

    Maksymova L Pilger YA Nuhn L Van Ginderachter JA . Nanobodies targeting the tumor microenvironment and their formulation as nanomedicines. Mol Cancer. (2025) 24:65. doi: 10.1186/s12943-025-02270-5

  • 14

    Li SR Tao SY Li Q Hu CY Sun ZJ . Harnessing nanomaterials for copper-induced cell death. Biomaterials. (2025) 313:122805. doi: 10.1016/j.biomaterials.2024.122805

  • 15

    Caputo D Quagliarini E Coppola A La Vaccara V Marmiroli B Sartori B et al . Inflammatory biomarkers and nanotechnology: new insights in pancreatic cancer early detection. Int J Surg. (2023) 109:2934–40. doi: 10.1097/JS9.0000000000000558

  • 16

    Nasrollahpour H Khalilzadeh B Hasanzadeh M Rahbarghazi R Estrela P Naseri A . Nanotechnology-based electrochemical biosensors for monitoring breast cancer biomarkers. Medicinal Res Rev. (2023) 43:464–569. doi: 10.1002/med.21931

  • 17

    Medici S Peana M Coradduzza D Zoroddu MA . Gold nanoparticles and cancer: Detection, diagnosis and therapy. Semin Cancer Biol. (2021) 76:2737. doi: 10.1016/j.semcancer.2021.06.017

  • 18

    Dastgheib ZS Abolmaali SS Farahavar G Salmanpour M Tamaddon AM . Gold nanostructures in melanoma: Advances in treatment, diagnosis, and theranostic applications. Heliyon. (2024) 10:e35655. doi: 10.1016/j.heliyon.2024.e35655

  • 19

    Nanda BP Rani P Paul P Aman Ganti SS Bhatia R . Recent trends and impact of localized surface plasmon resonance (LSPR) and surface-enhanced Raman spectroscopy (SERS) in modern analysis. J Pharm Anal. (2024) 14:100959. doi: 10.1016/j.jpha.2024.02.013

  • 20

    Xu T Geng Z . Strategies to improve performances of LSPR biosensing: Structure, materials, and interface modification. Biosens Bioelectron. (2021) 174:112850. doi: 10.1016/j.bios.2020.112850

  • 21

    Zhu D Liu Y Liu M Liu X Prasad PN Swihart MT . Galvanic replacement synthesis of multi-branched gold nanocrystals for photothermal cancer therapy. J Mater Chem B. (2020) 8:5491–9. doi: 10.1039/d0tb00748j

  • 22

    Mellor RD Uchegbu IF . Ultrasmall-in-nano: why size matters. Nanomater (Basel). (2022) 12:2476. doi: 10.3390/nano12142476

  • 23

    Ward LC Brantlov S . Bioimpedance basics and phase angle fundamentals. Rev Endocr Metab Disord. (2023) 24:381–91. doi: 10.1007/s11154-022-09780-3

  • 24

    Li Y Tang L Zhu C Liu X Wang X Liu Y . Fluorescent and colorimetric assay for determination of Cu(II) and Hg(II) using AuNPs reduced and wrapped by carbon dots. Mikrochim Acta. (2021) 189:10. doi: 10.1007/s00604-021-05111-6

  • 25

    Zhang L Mazouzi Y Salmain M Liedberg B Boujday S . Antibody-gold nanoparticle bioconjugates for biosensors: synthesis, characterization and selected applications. Biosens Bioelectron. (2020) 165:112370. doi: 10.1016/j.bios.2020.112370

  • 26

    Yin T Yang T Chen L Tian R Cheng C Weng L . Intelligent gold nanoparticles for Malignant tumor treatment via spontaneous copper manipulation and on-demand photothermal therapy based on copper induced click chemistry. Acta Biomater. (2023) 166:485–95. doi: 10.1016/j.actbio.2023.04.036

  • 27

    Cao J Lv P Shu Y Wang J . Aptamer/AuNPs encoders endow precise identification and discrimination of lipoprotein subclasses. Biosens Bioelectron. (2022) 196:113743. doi: 10.1016/j.bios.2021.113743

  • 28

    Taheri-Ledari R Zolfaghari E Zarei-Shokat S Kashtiaray A Maleki A . A magnetic antibody-conjugated nano-system for selective delivery of Ca(OH)2 and taxotere in ovarian cancer cells. Commun Biol. (2022) 5:995. doi: 10.1038/s42003-022-03966-w

  • 29

    S R M P . Multi-functional FITC-silica@gold nanoparticles conjugated with guar gum succinate, folic acid and doxorubicin for CT/fluorescence dual imaging and combined chemo/PTT of cancer. Colloids Surf B Biointerf. (2020) 186:110701. doi: 10.1016/j.colsurfb.2019.110701

  • 30

    Ide MS Davis RJ . The important role of hydroxyl on oxidation catalysis by gold nanoparticles. Accounts Chem Res. (2014) 47:825–33. doi: 10.1021/ar4001907

  • 31

    Zhang R Gao Y Wang S Pan J Geng S Li Z . Detection ofmiRNA-378based on a catalytic hairpin self-assembly reaction combined with gold nanoparticle colorimetry. Nanotechnology. (2024) 35. doi: 10.1088/1361-6528/ad5297

  • 32

    Kim H Park M Hwang J Kim JH Chung DR Lee KS . Development of label-free colorimetric assay for MERS-CoV using gold nanoparticles. ACS Sens. (2019) 4:1306–12. doi: 10.1021/acssensors.9b00175

  • 33

    Appidi T Mudigunda SV Kodandapani S Rengan AK . Development of label-free gold nanoparticle based rapid colorimetric assay for clinical/point-of-care screening of cervical cancer. Nanoscale Adv. (2020) 2:5737–45. doi: 10.1039/d0na00686f

  • 34

    Appidi T Vakada M Buddhiraju HS Chinchulkar SA Kota A Yadav DN . Development of a point-of-care cervico-vaginal sampling/testing device for the colorimetric detection of cervical cancer. Diagnost (Basel). (2023) 13:1382. doi: 10.3390/diagnostics13081382

  • 35

    Perkins RB Wentzensen N Guido RS Schiffman M . Cervical cancer screening: A review. JAMA. (2023) 330:547–58. doi: 10.1001/jama.2023.13174

  • 36

    Xiao H Chen W Lin M Jiang S Cui X Zhao S . Rapid immunoassay for dual-mode detection of HPV16 and HPV18 DNA based on Au@PdPt nanoparticles. Anal Methods. (2024) 16:1862–9. doi: 10.1039/d3ay02307a

  • 37

    Navarro Chica CE Alfonso Tobón LL López Abella JJ Valencia Piedrahita MP Neira Acevedo D Bermúdez PC . Nanoparticle-based colorimetric assays for early and rapid screening of the oncogenic HPV variants 16 and 18. Clin Chim Acta. (2025) 568:120144. doi: 10.1016/j.cca.2025.120144

  • 38

    Weng J Sheng N Wang R Liang S Wang C Bai X . Multiplex visualized closed-tube PCR with hamming distance 2 code for 15 HPV subtype typing. Anal Chem. (2021) 93:5529–36. doi: 10.1021/acs.analchem.1c00035

  • 39

    Yang Y Qing Y Hao X Fang C Ouyang P Li H . APTES-modified remote self-assembled DNA-based electrochemical biosensor for human papillomavirus DNA detection. Biosens (Basel). (2022) 12:449. doi: 10.3390/bios12070449

  • 40

    Kuntamung K Sangthong P Jakmunee J Ounnunkad K . Simultaneous immunodetection of multiple cervical cancer biomarkers based on a signal-amplifying redox probes/polyethyleneimine-coated gold nanoparticles/2D tungsten disulfide/graphene oxide nanocomposite platform. Bioelectrochemistry. (2024) 160:108780. doi: 10.1016/j.bioelechem.2024.108780

  • 41

    Su S Sun Q Ma J Zhu D Wang F Chao J . Ultrasensitive analysis of microRNAs with gold nanoparticle-decorated molybdenum disulfide nanohybrid-based multilayer nanoprobes. Chem Commun (Camb). (2020) 56:9012–5. doi: 10.1039/d0cc03845h

  • 42

    Zhang JX Lv CL Tang C Jiang LY Wang AJ Feng JJ . Ultrasensitive sandwich-typed electrochemical immunoassay for detection of squamous cell carcinoma antigen based on highly branched PtCo nanocrystals and dendritic mesoporous SiO2@AuPt nanoparticles. Mikrochim Acta. (2022) 189:416. doi: 10.1007/s00604-022-05520-1

  • 43

    Kotal H Kalyani T Lala A R K Mandal RK Jana SK . Development of a highly sensitive, label-free electrochemical immunosensor for p16INK4a detection: a step toward early cervical cancer diagnosis. Anal Methods. (2025) 17:4556–65. doi: 10.1039/d5ay00411j

  • 44

    Zamudio Cañas R Jaramillo Flores ME Vallejo Ruiz V Delgado Macuil RJ López Gayou V . Detection of sialic acid to differentiate cervical cancer cell lines using a Sambucus nigra lectin biosensor. Biosens (Basel). (2024) 14:34. doi: 10.3390/bios14010034

  • 45

    Saleh MA Zangeneh FZ Borghei YS Samadikhah HR Nikkhah M Hosseinkhani S . Detection of HPV-16 by a simple and cost-effective DNA probe: polyadenine-polythymine-decorated gold nanoparticles (PolyA-polyT@AuNPs). Biotechnol Appl Biochem. (2025), e2772. doi: 10.1002/bab.2772

  • 46

    Yang Y Liao Y Qing Y Li H Du J . Electrochemical DNA biosensors with dual-signal amplification strategy for highly sensitive HPV 16 detection. Sens (Basel). (2023) 23:7380. doi: 10.3390/s23177380

  • 47

    Mahmoodi P Rezayi M Rasouli E Avan A Gholami M Ghayour Mobarhan M . Early-stage cervical cancer diagnosis based on an ultra-sensitive electrochemical DNA nanobiosensor for HPV-18 detection in real samples. J Nanobiotechnol. (2020) 18:11. doi: 10.1186/s12951-020-0577-9

  • 48

    Yang N Liu P Cai C Zhang R Sang K Shen P . Triple signal amplification strategy for the ultrasensitive electrochemical detection of human papillomavirus 16 E6/E7 mRNA. Enzyme Microb Technol. (2021) 149:109855. doi: 10.1016/j.enzmictec.2021.109855

  • 49

    Jaapar FN Parmin NA Halim NHA Hashim U Gopinath SCB Halim FS . Micro-interdigitated electrodes genosensor based on Au-deposited nanoparticles for early detection of cervical cancer. Int J Biol Macromol. (2023) 253:126745. doi: 10.1016/j.ijbiomac.2023.126745

  • 50

    Shahdeo D Kesarwani V Suhag D Ahmed J Alshehri SM Gandhi S . Self-assembled chitosan polymer intercalating peptide functionalized gold nanoparticles as nanoprobe for efficient imaging of urokinase plasminogen activator receptor in cancer diagnostics. Carbohydr Polym. (2021) 266:118138. doi: 10.1016/j.carbpol.2021.118138

  • 51

    Avelino KYPS Oliveira LS Lucena-Silva N de Melo CP Andrade CAS Oliveira MDL . Metal-polymer hybrid nanomaterial for impedimetric detection of human papillomavirus in cervical specimens. J Pharm BioMed Anal. (2020) 185:113249. doi: 10.1016/j.jpba.2020.113249

  • 52

    Sun Y Liu J Peng X Zhang G Li Y . A novel photoelectrochemical array platform for ultrasensitive multiplex detection and subtype identification of HPV genes. Biosens Bioelectron. (2023) 224:115059. doi: 10.1016/j.bios.2023.115059

  • 53

    Li L Tian H Wang G Ren S Ma T Wang Y . Ready-to-use interactive dual-readout differential lateral flow biosensor for two genotypes of human papillomavirus. Biosens Bioelectron. (2023) 228:115224. doi: 10.1016/j.bios.2023.115224

  • 54

    Hu J Yu Y Pan X Han Y She X Liu X . Highly sensitive and specific detection of human papillomavirus type 16 using CRISPR/Cas12a assay coupled with an enhanced single nanoparticle dark-field microscopy imaging technique. Talanta. (2024) 278:126449. doi: 10.1016/j.talanta.2024.126449

  • 55

    Lu D Ran M Liu Y Xia J Bi L Cao X . SERS spectroscopy using Au-Ag nanoshuttles and hydrophobic paper-based Au nanoflower substrate for simultaneous detection of dual cervical cancer-associated serum biomarkers. Anal Bioanal Chem. (2020) 412:7099–112. doi: 10.1007/s00216-020-02843-x

  • 56

    Panikar SS Banu N Haramati J Gutierrez-Silerio GY Bastidas-Ramirez BE Tellez-Bañuelos MC . Anti-fouling SERS-based immunosensor for point-of-care detection of the B7-H6 tumor biomarker in cervical cancer patient serum. Anal Chim Acta. (2020) 1138:110–22. doi: 10.1016/j.aca.2020.09.019

  • 57

    Ge S Ran M Mao Y Sun Y Zhou X Li L . A novel DNA biosensor for the ultrasensitive detection of DNA methyltransferase activity based on a high-density “hot spot” SERS substrate and rolling circle amplification strategy. Analyst. (2021) 146:5326–36. doi: 10.1039/d1an01034d

  • 58

    Gu Y Li Z Ge S Mao Y Gu Y Cao X . A microfluidic chip using Au@SiO2 array-based highly SERS-active substrates for ultrasensitive detection of dual cervical cancer-related biomarkers. Anal Bioanal Chem. (2022) 414:7659–73. doi: 10.1007/s00216-022-04296-w

  • 59

    Karunakaran V Saritha VNS Ramya AN Murali VP Raghu KG Sujathan K . Elucidating raman image-guided differential recognition of clinically confirmed grades of cervical exfoliated cells by dual biomarker-appended SERS-tag. Anal Chem. (2021) 93:11140–50. doi: 10.1021/acs.analchem.1c01607

  • 60

    Li Y Jiang L Yu Z Jiang C Zhang F Jin S . SPRi/SERS dual-mode biosensor based on ployA-DNA/miRNA/AuNPs-enhanced probe sandwich structure for the detection of multiple miRNA biomarkers. Spectrochim Acta A Mol Biomol Spectrosc. (2024) 308:123664. doi: 10.1016/j.saa.2023.123664

  • 61

    Karunakaran V Saritha VNS Joseph MM Nair JB Saranya G Raghu KG . Diagnostic spectro-cytology revealing differential recognition of cervical cancer lesions by label-free surface enhanced Raman fingerprints and chemometrics. Nanomed-nanotechnol. (2020) 29:102276. doi: 10.1016/j.nano.2020.102276

  • 62

    Diao X Li X Hou S Li H Qi G Jin Y . Machine learning-based label-free SERS profiling of exosomes for accurate fuzzy diagnosis of cancer and dynamic monitoring of drug therapeutic processes. Anal Chem. (2023) 95:7552–9. doi: 10.1021/acs.analchem.3c00026

  • 63

    Li H Wang Q Tang J Gao NN Yue XX Zhong FR . Establishment of a reliable scheme for obtaining highly stable SERS signal of biological serum. Biosens Bioelectron. (2021) 189:113315. doi: 10.1016/j.bios.2021.113315

  • 64

    Diao X Qi G Tian Y Li J Jin Y . Gap-plasmon metasurface combined with bio-barcode of CD63 nanoflares for SERS detection of cancerous exosomes. Anal Chem. (2025) 97:13958–64. doi: 10.1021/acs.analchem.5c02115

  • 65

    Yin HQ Shao G Gan F Ye G . One-step, rapid and green synthesis of multifunctional gold nanoparticles for tumor-targeted imaging and therapy. Nanoscale Res Lett. (2020) 15:29. doi: 10.1186/s11671-019-3232-3

  • 66

    Yim MS Hwang YS Bang JK Jung DW Kim JM Yi GR . Morphologically homogeneous, pH-responsive gold nanoparticles for non-invasive imaging of HeLa cancer. Nanomedicine. (2021) 34:102394. doi: 10.1016/j.nano.2021.102394

  • 67

    Zhang W Lu Y Zang Y Han J Xiong Q Xiong J . Photodynamic therapy and multi-modality imaging of up-conversion nanomaterial doped with AuNPs. Int J Mol Sci. (2022) 23:1227. doi: 10.3390/ijms23031227

  • 68

    Wang J Huang M Li MX Zhu F Cheng R Liu JJ . The restructure of Au@Ag nanorods for cell imaging with dark-field microscope. Talanta. (2022) 244:123403. doi: 10.1016/j.talanta.2022.123403

  • 69

    Yücel O Şengelen A Emik S Önay-Uçar E Arda N Gürdağ G . Folic acid-modified methotrexate-conjugated gold nanoparticles as nano-sized trojans for drug delivery to folate receptor-positive cancer cells. Nanotechnology. (2020) 31:355101. doi: 10.1088/1361-6528/ab9395

  • 70

    Velhal K Sah PM Naik HS Raut R Patil S Yamgar R . Synergistic nanoformulation: streamlined one-pot synthesis enhances paclitaxel functionalization gold nanoparticles for potent anticancer activity. Cell Biochem Biophys. (2025). doi: 10.1007/s12013-025-01701-w

  • 71

    Matić IZ Mraković A Rakočević Z Stoiljković M Pavlović VB Momić T . Anticancer effect of novel luteolin capped gold nanoparticles selectively cytotoxic towards human cervical adenocarcinoma HeLa cells: An in vitro approach. J Trace Elem Med Biol. (2023) 80:127286. doi: 10.1016/j.jtemb.2023.127286

  • 72

    Lopes-Nunes J Agonia AS Rosado T Gallardo E Palmeira-de-Oliveira R Palmeira-de-Oliveira A . Aptamer-functionalized gold nanoparticles for drug delivery to gynecological carcinoma cells. Cancers (Basel). (2021) 13:4038. doi: 10.3390/cancers13164038

  • 73

    Farooq MU Dovzhenko AP Zairov RR Abyzbekova G Harb M Arkook B . Insights into the engineered gold nanoparticle-based remedy for supplementation therapy of ovarian carcinoma. ACS Omega. (2024) 9:33033–43. doi: 10.1021/acsomega.4c04134

  • 74

    Fathy MM Elfiky AA Bashandy YS Hamdy MM Elgharib AM Ibrahim IM . An insight into synthesis and antitumor activity of citrate and gallate stabilizing gold nanospheres. Sci Rep-uk. (2023) 13:2749. doi: 10.1038/s41598-023-29821-4

  • 75

    Srinivas Naik L Devi CVR . Induction of extrinsic and intrinsic apoptosis in cervical cancer cells by Momordica dioica mediated gold nanoparticles. IET Nanobiotechnol. (2020) 14:172–9. doi: 10.1049/iet-nbt.2019.0075

  • 76

    Prasad A Khatua A Mohanta YK Saravanan M Meena R Ghosh I . Low-dose exposure to phytosynthesized gold nanoparticles combined with glutamine deprivation enhances cell death in the cancer cell line HeLa via oxidative stress-mediated mitochondrial dysfunction and G0/G1 cell cycle arrest. Nanoscale. (2022) 14:10399–417. doi: 10.1039/d2nr02150a

  • 77

    Kamil Shareef NA Zandsalimi F Tavoosidana G . Gold nanoparticles (AuNPs) decrease the viability of cervical cancer cells by inducing the BAX gene and activating antioxidant enzymes. Mol Biol Rep. (2024) 51:287. doi: 10.1007/s11033-024-09253-7

  • 78

    Jung DW Ro HJ Kim J Kim SI Yi GR Lee G . Biophysical restriction of growth area using a monodispersed gold sphere nanobarrier prolongs the mitotic phase in HeLa cells. RSC Adv. (2019) 9:37497–506. doi: 10.1039/c9ra08410j

  • 79

    Liu P Wang Y Liu Y Tan F Li J Li N . S-nitrosothiols loaded mini-sized Au@silica nanorod elicits collagen depletion and mitochondrial damage in solid tumor treatment. Theranostics. (2020) 10:6774–89. doi: 10.7150/thno.42661

  • 80

    Imanparast A Attaran N Eshghi H Sazgarnia A . Surface modification of gold nanoparticles with 6-mercapto-1-hexanol to facilitate dual conjugation of protoporphyrin IX and folic acid for improving the targeted photochemical internalization. Iran J Basic Med Sci. (2022) 25:970–9. doi: 10.22038/IJBMS.2022.63622.14033

  • 81

    Teixeira ARC Antunes J Pinto CIG Cabral Campello MP Santos P Gomes CéM . GRPR-targeted gold nanoparticles as selective radiotherapy enhancers in glioblastoma. Phys Med Biol. (2025) 70. doi: 10.1088/1361-6560/ade222

  • 82

    Liu J Liang Y Liu T Li D Yang X . Anti-EGFR-conjugated hollow gold nanospheres enhance radiocytotoxic targeting of cervical cancer at megavoltage radiation energies. Nanoscale Res Lett. (2015) 10:218. doi: 10.1186/s11671-015-0923-2

  • 83

    Amani S Mehdizadeh A Movahedi MM Keshavarz M Koosha F . Investigation of the dose-Enhancement effects of spherical and rod-Shaped gold nanoparticles on the HeLa cell line. Galen Med J. (2020) 4:e1581. doi: 10.31661/gmj.v9i0.1581

  • 84

    Gray TM David S Bassiri N Patel DY Kirby N Mayer KM . Microdosimetric and radiobiological effects of gold nanoparticles at therapeutic radiation energies. Int J Radiat Biol. (2023) 99:308–17. doi: 10.1080/09553002.2022.2087931

  • 85

    Aydindogan E Ceylan AE Timur S . Paper-based colorimetric spot test utilizing smartphone sensing for detection of biomarkers. Talanta. (2020) 208:120446. doi: 10.1016/j.talanta.2019.120446

  • 86

    Liu H Wu MX Ding SN . High-density gold nanoparticles implanted on Mg/Fe LDH nanoflowers assisted lateral flow immuno-dipstick assay for visual detection of human epididymal protein 4. Biosens (Basel). (2022) 12:797. doi: 10.3390/bios12100797

  • 87

    Ibadi I Naseri A Khalilzadeh B . Development of an electrochemical biosensor based on MOF@AuNPs nanocomposite for early-stage evaluation of ovarian cancer via CA125 oncomarker in human serum samples. Sens Bio Sens Res. (2025) 49:100838. doi: 10.1016/j.sbsr.2025.100838

  • 88

    Gharehaghaji ZH Khalilzadeh B Yousefi H Mohammad-Rezaei R . An electrochemical immunosensor based on MXene-GQD/AuNPs for the detection of trace amounts of CA-125 as specific tracer of ovarian cancer. Mikrochim Acta. (2024) 191:418. doi: 10.1007/s00604-024-06469-z

  • 89

    Shen R Zhang J Huang W Wu S Li G Zou S . Dynamic light scattering and fluorescence dual-signal sensing of cancer antigen-125 via recognition of the polymerase chain reaction product with gold nanoparticle probe. Anal Chim Acta. (2021) 1145:8794. doi: 10.1016/j.aca.2020.11.005

  • 90

    Cotchim S Thavarungkul P Kanatharana P Thantipwan T Jiraseree-Amornkun A Wannapob R . A portable electrochemical immunosensor for ovarian cancer uses hierarchical microporous carbon material from waste coffee grounds. Mikrochim Acta. (2023) 190:232. doi: 10.1007/s00604-023-05798-9

  • 91

    Tang Y Liu Y Xia Y Zhao F Zeng B . Simultaneous detection of ovarian cancer-concerned HE4 and CA125 markers based on cu single-atom-triggered CdS QDs and Eu MOF@Isoluminol ECL. Anal Chem. (2023) 95:4795–802. doi: 10.1021/acs.analchem.3c00273

  • 92

    Samadi Pakchin P Fathi M Ghanbari H Saber R Omidi Y . A novel electrochemical immunosensor for ultrasensitive detection of CA125 in ovarian cancer. Biosens Bioelectron. (2020) 153:112029. doi: 10.1016/j.bios.2020.112029

  • 93

    Hu D Liang H Wang X Luo F Qiu B Lin Z . Highly sensitive and selective photoelectrochemical aptasensor for cancer biomarker CA125 based on AuNPs/GaN Schottky junction. Anal Chem. (2020) 92:10114–20. doi: 10.1021/acs.analchem.0c02117

  • 94

    Xu X Ji J Chen P Wu J Jin Y Zhang L . Salt-induced gold nanoparticles aggregation lights up fluorescence of DNA-silver nanoclusters to monitor dual cancer markers carcinoembryonic antigen and carbohydrate antigen 125. Anal Chim Acta. (2020) 1125:41–9. doi: 10.1016/j.aca.2020.05.027

  • 95

    Jin W Chen R Wu L Peng C Song Y Miao L . Tetrahedral DNA nanostructure enhanced toehold-mediated strand displacement for highly sensitive electrochemiluminescence assay of CA125. Bioelectrochemistry. (2024) 155:108572. doi: 10.1016/j.bioelechem.2023.108572

  • 96

    Amirabadizadeh M Siampour H Abbasian S Nikkhah M Moshaii A . Aptasensor for ovarian cancer biomarker detection using nanostructured gold electrodes. Mikrochim Acta. (2023) 191:2. doi: 10.1007/s00604-023-06072-8

  • 97

    Bilgi Kamaç M Altun M Yilmaz M Sezgintürk MK . A label-free dual immunosensor for the simultaneous electrochemical determination of CA125 and HE4 biomarkers for the early diagnosis of ovarian cancer. Anal Bioanal Chem. (2023) 415:1709–18. doi: 10.1007/s00216-023-04569-y

  • 98

    Yılmaz M Bilgi M . A disposable impedimetric immunosensor for the analysis of CA125 in human serum samples. BioMed Microdevices. (2024) 26:8. doi: 10.1007/s10544-023-00691-x

  • 99

    Jin W Chen R Wu L Peng C Song Y Miao L . An “on-off” electrochemical immunosensor for the detection of the glycan antigen CA125 by amplification signals using electropositive COFs. Talanta. (2025) 286:127593. doi: 10.1016/j.talanta.2025.127593

  • 100

    Dezhakam E Dehghani S Faraghi Vayghan R Naseri A Khalilzadeh B Isildak I . An early stage electrochemical evaluation of ovarian cancer: α-MnO2 nanorod and AuNP hybrid nanoarchitectures. Langmuir. (2025) 41:17573–83. doi: 10.1021/acs.langmuir.5c01178

  • 101

    Mu W Wu C Wu F Gao H Ren X Feng J . Ultrasensitive and label-free electrochemical immunosensor for the detection of the ovarian cancer biomarker CA125 based on CuCo-ONSs@AuNPs nanocomposites. J Pharm BioMed Anal. (2024) 243:116080. doi: 10.1016/j.jpba.2024.116080

  • 102

    Asare-Werehene M Hunter RA Gerber E Reunov A Brine I Chang CY et al . The application of an extracellular vesicle-based biosensor in early diagnosis and prediction of chemoresponsiveness in ovarian cancer. Cancers. (2023) 15:2566. doi: 10.3390/cancers15092566

  • 103

    Samanci SN Ozcelikay-Akyildiz G Bellur Atici E Ozkan SA . Advanced sensor technologies for niraparib detection: A comparative study of molecularly imprinted polymer and nanosensor systems. Talanta. (2025) 294:128205. doi: 10.1016/j.talanta.2025.128205

  • 104

    Kang Y Masud MK Guo Y Zhao Y Nishat ZS Zhao J . Au-loaded superparamagnetic mesoporous bimetallic CoFeB nanovehicles for sensitive autoantibody detection. ACS Nano. (2023) 17:3346–57. doi: 10.1021/acsnano.2c07694

  • 105

    Chen D Wu Y Tilley RD Gooding JJ . Rapid and ultrasensitive electrochemical detection of DNA methylation for ovarian cancer diagnosis. Biosens Bioelectron. (2022) 206:114126. doi: 10.1016/j.bios.2022.114126

  • 106

    Liu X Wang Q Chen J Chen X Yang W . Ultrasensitive electrochemiluminescence biosensor for the detection of tumor exosomes based on peptide recognition and luminol-AuNPs@g-C3N4 nanoprobe signal amplification. Talanta. (2021) 221:121379. doi: 10.1016/j.talanta.2020.121379

  • 107

    Xu X Tang L Yu Y Zhang J Zhou X Zhou T . Cooperative amplification of PRussian blue as a signal indicator and functionalized metal-organic framework-based electrochemical biosensor for an ultrasensitive HE4 assay. Biosens Bioelectron. (2024) 262:116541. doi: 10.1016/j.bios.2024.116541

  • 108

    Rockett TW Almahyawi M Ghimire ML Jonnalagadda A Tagliaferro V Seashols-Williams SJ . Cluster-enhanced nanopore sensing of ovarian cancer marker peptides in urine. ACS Sens. (2024) 9:860–9. doi: 10.1021/acssensors.3c02207

  • 109

    Beffara F Perumal J Mahyuddin AP Choolani M Khan SA Auguste JL . Development of highly reliable SERS-active photonic crystal fiber probe and its application in the detection of ovarian cancer biomarker in cyst fluid. J Biophotonics. (2020) 13:e201960120. doi: 10.1002/jbio.201960120

  • 110

    Kahn N Lavie O Paz M Segev Y Haick H . Dynamic nanoparticle-based flexible sensors: diagnosis of ovarian carcinoma from exhaled breath. Nano Lett. (2015) 15:7023–8. doi: 10.1021/acs.nanolett.5b03052

  • 111

    Kumar D Sakhare N Das S Kale P Mathur A Mirapurkar S . Development of technetium-99m labeled ultrafine gold nanobioconjugates for targeted imaging of folate receptor positive cancers. Nucl Med Biol. (2021) 93:110. doi: 10.1016/j.nucmedbio.2020.11.001

  • 112

    Beik J Alamzadeh Z Mirrahimi M Sarikhani A Shakerian Ardakani T Asadi MR . Multifunctional theranostic graphene oxide nanoflakes as MR imaging agents with enhanced photothermal and radiosensitizing properties. ACS Appl Bio Mater. (2021) 4:4280–91. doi: 10.1021/acsabm.1c00104

  • 113

    Kumar D Moghiseh M Chitcholtan K Mutreja I Lowe C Kaushik A . LHRH conjugated gold nanoparticles assisted efficient ovarian cancer targeting evaluated via spectral photon-counting CT imaging: a proof-of-concept research. J Mater Chem B. (2023) 11:1916–28. doi: 10.1039/d2tb02416k

  • 114

    Hada AM Craciun AM Focsan M Borlan R Soritau O Todea M . Folic acid functionalized gold nanoclusters for enabling targeted fluorescence imaging of human ovarian cancer cells. Talanta. (2021) 225:121960. doi: 10.1016/j.talanta.2020.121960

  • 115

    Taheri-Ledari R Zhang W Radmanesh M Cathcart N Maleki A Kitaev V . Plasmonic photothermal release of docetaxel by gold nanoparticles incorporated onto halloysite nanotubes with conjugated 2D8-E3 antibodies for selective cancer therapy. J Nanobiotechnol. (2021) 19:239. doi: 10.1186/s12951-021-00982-6

  • 116

    Verdin A Malherbe C Müller WH Bertrand V Eppe G . Multiplex micro-SERS imaging of cancer-related markers in cells and tissues using poly(allylamine)-coated Au@Ag nanoprobes. Anal Bioanal Chem. (2020) 412:7739–55. doi: 10.1007/s00216-020-02927-8

  • 117

    Honda K Hish T . On-tissue polysulfide visualization by surface-enhanced Raman spectroscopy benefits patients with ovarian cancer to predict post-operative chemosensitivity. Redox Biol. (2021) 41:101926. doi: 10.1016/j.redox.2021.101926

  • 118

    Lee CS Kim TW Oh DE Bae SO Ryu J Kong H . In vivo and in vitro anticancer activity of doxorubicin-loaded DNA-AuNP nanocarrier for the ovarian cancer treatment. Cancers (Basel). (2020) 12:634. doi: 10.3390/cancers12030634

  • 119

    Hossen MN Wang L Chinthalapally HR Robertson JD Fung KM Wilhelm S . Switching the intracellular pathway and enhancing the therapeutic efficacy of small interfering RNA by auroliposome. Sci Adv. (2020) 6:eaba5379. doi: 10.1126/sciadv.aba5379

  • 120

    Jabir M Sahib UI Taqi Z Taha A Sulaiman G Albukhaty S . Linalool-loaded glutathione-modified gold nanoparticles conjugated with CALNN peptide as apoptosis inducer and NF-κB translocation inhibitor in SKOV-3 cell line. Int J Nanomed. (2020) 15:9025–47. doi: 10.2147/IJN.S276714

  • 121

    Tunc CU Kursunluoglu G Akdeniz M Kutlu AU Han MI Yerer MB . Investigation of gold nanoparticle naproxen-derived conjugations in ovarian cancer. ACS Mater Au. (2023) 3:483–91. doi: 10.1021/acsmaterialsau.3c00033

  • 122

    Salas-Huenuleo E Hernández A Lobos-González L Polakovičová I Morales-Zavala F Araya E . Peptide targeted gold nanoplatform carrying miR-145 induces antitumoral effects in ovarian cancer cells. Pharmaceutics. (2022) 14:958. doi: 10.3390/pharmaceutics14050958

  • 123

    Wang Z Zhao Y Yang Z Li X Xing H Qu W . Construction of intelligent responsive drug delivery system and multi-mode imaging based on gold nanodots. Macromol Rapid Commun. (2022) 43:e2200034. doi: 10.1002/marc.202200034

  • 124

    Piktel E Oscilowska I Suprewicz Ł Depciuch J Marcińczyk N Chabielska E . Peanut-shaped gold nanoparticles with shells of ceragenin CSA-131 display the ability to inhibit ovarian cancer growth in vitro and in a tumor xenograft model. Cancers (Basel). (2021) 13:5424. doi: 10.3390/cancers13215424

  • 125

    Maity R Chatterjee M Banerjee A Das A Mishra R Mazumder S . Gold nanoparticle-assisted enhancement in the anti-cancer properties of theaflavin against human ovarian cancer cells. Mater Sci Eng C Mater Biol Appl. (2019) 104:109909. doi: 10.1016/j.msec.2019.109909

  • 126

    Salamone TA Marotta S Mrmić S Raffa S Cerra S Pennacchi B . MiR-200c synergizes with trastuzumab-loaded gold nanoparticles to overcome resistance in ovarian cancer cells. Cancer Nanotechnol. (2025) 16:29. doi: 10.1186/s12645-025-00330-5

  • 127

    Torres J Calderón-Montaño JM Prieto-Dapena F López-Lázaro M Rueda M Rabasco-Álvarez AM . A quality-by-design approach for optimizing the functionalization of gold nanoparticles onto the surface of doxorubicin-encapsulated liposomes. Int J Pharm. (2025) 669:125040. doi: 10.1016/j.ijpharm.2024.125040

  • 128

    Wang X Xiong T Cui M Li N Li Q Zhu L . A novel targeted co-delivery nanosystem for enhanced ovarian cancer treatment via multidrug resistance reversion and mTOR-mediated signaling pathway. J Nanobiotechnol. (2021) 19:444. doi: 10.1186/s12951-021-01139-1

  • 129

    Kip B Tunc CU Aydin O . Triple-combination therapy assisted with ultrasound-active gold nanoparticles and ultrasound therapy against 3D cisplatin-resistant ovarian cancer model. Ultrason Sonochem. (2022) 82:105903. doi: 10.1016/j.ultsonch.2021.105903

  • 130

    Arvizo RR Saha S Wang E Robertson JD Bhattacharya R Mukherjee P . Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle. Proc Natl Acad Sci U S A. (2013) 110:6700–5. doi: 10.1073/pnas.1214547110

  • 131

    Hossen MN Wang L Dwivedi SKD Zhang Y Rao G Elechalwar CK . Gold nanoparticles disrupt the IGFBP2/mTOR/PTEN axis to inhibit ovarian cancer growth. Adv Sci (Weinh). (2022) 9:e2200491. doi: 10.1002/advs.202200491

  • 132

    Zhang Y Elechalawar CK Yang W Frickenstein AN Asfa S Fung KM . Disabling partners in crime: Gold nanoparticles disrupt multicellular communications within the tumor microenvironment to inhibit ovarian tumor aggressiveness. Mater Today (Kidlington). (2022) 56:7995. doi: 10.1016/j.mattod.2022.01.025

  • 133

    Zhang Y Elechalwar CK Hossen MN Francek ER Dey A Wilhelm S . Gold nanoparticles inhibit activation of cancer-associated fibroblasts by disrupting communication from tumor and microenvironmental cells. Bioact Mater. (2021) 6:326–32. doi: 10.1016/j.bioactmat.2020.08.009

  • 134

    Zhang Y Xiong X Huai Y Dey A Hossen MN Roy RV . Gold nanoparticles disrupt tumor microenvironment - endothelial cell cross talk to inhibit angiogenic phenotypes in vitro. Bioconjug Chem. (2019) 30:1724–33. doi: 10.1021/acs.bioconjchem.9b00262

  • 135

    Zhang M Zheng H Zhu X Liu S Jin H Chen Y . Synchronously evoking disulfidptosis and ferroptosis via systematical glucose deprivation targeting SLC7A11/GSH/GPX4 antioxidant axis. ACS Nano. (2025) 19:14233–48. doi: 10.1021/acsnano.5c00730

  • 136

    Ali MRK Wu Y Ghosh D Do BH Chen K Dawson MR . Nuclear membrane-targeted gold nanoparticles inhibit cancer cell migration and invasion. ACS Nano. (2017) 11:3716–26. doi: 10.1021/acsnano.6b08345

  • 137

    Asl SS Tafvizi F Noorbazargan H . Biogenic synthesis of gold nanoparticles using Satureja rechingeri Jamzad: a potential anticancer agent against cisplatin-resistant A2780CP ovarian cancer cells. Environ Sci pollut Res Int. (2023) 30:20168–84. doi: 10.1007/s11356-022-23507-6

  • 138

    Piktel E Ościłowska I Suprewicz Ł Depciuch J Marcińczyk N Chabielska E . ROS-mediated apoptosis and autophagy in ovarian cancer cells treated with peanut-shaped gold nanoparticles. Int J Nanomed. (2021) 16:19932011. doi: 10.2147/IJN.S277014

  • 139

    Malik IS Nair NK B A Mishra S Unnithan S Narayana C . Optimizing branch morphology in gold nanostars to improve HER2-targeted cytotoxicity in HER2-overexpressing cancer cells in the presence of serum proteins. Langmuir. (2025) 41:15796–804. doi: 10.1021/acs.langmuir.5c00350

  • 140

    Wei Q Arami H Santos Zhang H Li Y He J . Intraoperative assessment and photothermal ablation of the tumor margins using gold nanoparticles. Adv Sci (Weinh). (2021) 8:2002788. doi: 10.1002/advs.202002788

  • 141

    Shen Y Wang M Wang H Zhou J Chen J . Multifunctional human serum albumin fusion protein as a docetaxel nanocarrier for chemo-photothermal synergetic therapy of ovarian cancer. ACS Appl Mater Interf. (2022) 14:19907–17. doi: 10.1021/acsami.2c03687

  • 142

    Wang Z Sun X Huang T Song J Wang Y . A sandwich nanostructure of gold nanoparticle coated reduced graphene oxide for photoacoustic imaging-guided photothermal therapy in the second NIR window. Front Bioeng Biotech. (2020) 8:655. doi: 10.3389/fbioe.2020.00655

  • 143

    Choe HS Shin MJ Kwon SG Lee H Kim DK Choi KU . Yolk-shell-type gold nanoaggregates for chemo- and photothermal combination therapy for drug-resistant cancers. ACS Appl Mater Interf. (2021) 13:53519–29. doi: 10.1021/acsami.1c10036

  • 144

    Rokhgireh S Chaichian S Mehdizadeh Kashi A Haji Ali B Tehermanesh K Ajdary M . Curcumin-gold nanoshell mediated near-infrared irradiation on human ovarian cancer cell: in vitro study. Med Oncol. (2025) 42:145. doi: 10.1007/s12032-025-02687-4

  • 145

    Zhao J Tu K Liu Y Qin Y Wang X Qi L . Photo-controlled aptamers delivery by dual surface gold-magnetic nanoparticles for targeted cancer therapy. Mater Sci Eng C Mater Biol Appl. (2017) 80:8892. doi: 10.1016/j.msec.2017.04.044

  • 146

    Liu A Li L Wang Z Li X Liang H Yang J . Ultrasmall Au-GRHa nanosystem for FL/CT dual-mode imaging-guided targeting photothermal therapy of ovarian cancer. Anal Chem. (2025) 97:2232–43. doi: 10.1021/acs.analchem.4c05320

  • 147

    Ma X Zhou W Zhang R Zhang C Yan J Feng J . Minimally invasive injection of biomimetic Nano@Microgel for in situ ovarian cancer treatment through enhanced photodynamic reactions and photothermal combined therapy. Mater Today Bio. (2023) 20:100663. doi: 10.1016/j.mtbio.2023.100663

  • 148

    Geng F Song K Xing JZ Yuan C Yan S Yang Q . Thio-glucose bound gold nanoparticles enhance radio-cytotoxic targeting of ovarian cancer. Nanotechnology. (2011) 22:285101. doi: 10.1088/0957-4484/22/28/285101

  • 149

    Żelechowska-Matysiak K Wawrowicz K Wierzbicki M Budlewski T Bilewicz A Majkowska-Pilip A . Radiobioconjugate of kadcyla with radioactive gold nanoparticles for targeted therapy of HER2-overexpressing cancers. Mol Pharmaceut. (2025) 22:4019–31. doi: 10.1021/acs.molpharmaceut.5c00288

  • 150

    McDougall RM Cahill HF Power ME MacCormack TJ Meli MV Rourke JL . Multiparametric cytotoxicity assessment: the effect of gold nanoparticle ligand functionalization on SKOV3 ovarian carcinoma cell death. Nanotoxicology. (2022) 16:355–74. doi: 10.1080/17435390.2022.2095312

  • 151

    Baran MF Keskin C Baran A Eftekhari A Omarova S Khalilov R . The investigation of the chemical composition and applicability of gold nanoparticles synthesized with amygdalus communis (Almond) leaf aqueous extract as antimicrobial and anticancer agents. Molecules. (2023) 28:2428. doi: 10.3390/molecules28062428

  • 152

    Sani A Cao C Cui D . Toxicity of gold nanoparticles (AuNPs): A review. Biochem Biophys Rep. (2021) 26:100991. doi: 10.1016/j.bbrep.2021.100991

  • 153

    Poley M Mora-Raimundo P Shammai Y Kaduri M Koren L Adir O . Nanoparticles accumulate in the female reproductive system during ovulation affecting cancer treatment and fertility. ACS Nano. (2022) 16:5246–57. doi: 10.1021/acsnano.1c07237

  • 154

    Guo WB Wu C Yang L Miao AJ . Pre-exposure to titanium or iron oxide nanoparticles suppresses the subsequent cellular uptake of gold nanoparticles. Sci Total Environ. (2023) 875:162491. doi: 10.1016/j.scitotenv.2023.162491

  • 155

    García MC Naitlho N Calderón-Montaño JM Drago E Rueda M Longhi M . Cholesterol levels affect the performance of AuNPs-decorated thermo-sensitive liposomes as nanocarriers for controlled doxorubicin delivery. Pharmaceutics. (2021) 13:973. doi: 10.3390/pharmaceutics13070973

  • 156

    Dai Q Wilhelm S Ding D Syed AM Sindhwani S Zhang Y . Quantifying the ligand-coated nanoparticle delivery to cancer cells in solid tumors. ACS Nano. (2018) 12:8423–35. doi: 10.1021/acsnano.8b03900

  • 157

    Manivasagan P Oh J . Production of a novel fucoidanase for the green synthesis of gold nanoparticles by streptomyces sp. and its cytotoxic effect on HeLa cells. Mar Drugs. (2015) 13:6818–37. doi: 10.3390/md13116818

  • 158

    Suh DH Lee SJ Kim H Song KY Jo JY Chae SJ . Effect of CO2 fractional laser preTreatment in photothermal therapy using ethosome gold nanoparticles: A preliminary study. J Cosmet Dermatol. (2025) 24:e70349. doi: 10.1111/jocd.70349

  • 159

    Ramírez-Nava G Santos-Cuevas C Ferro-Flores G Ocampo-García B Chairez I Gómez-Argumosa E . Hybrid (2D/3D) dosimetry of radiolabeled gold nanoparticles for sentinel lymph node detection in patients with breast cancer. Contrast Media Mol Imaging. (2020) 2020:2728134. doi: 10.1155/2020/2728134

  • 160

    Khoobchandani M Katti KK Karikachery AR Thipe VC Srisrimal D Mohandoss DKD . New approaches in breast cancer therapy through green nanotechnology and nano-ayurvedic medicine - pre-clinical and pilot human clinical investigations. Int J Nanomed. (2020) 15:181–97. doi: 10.2147/IJN.S219042

  • 161

    Choi YJ Kim JS Kim WS . Photothermal therapy using gold nanoparticles and a long-pulsed 755-nm alexandrite laser to treat facial photoaging in Asian skin: A prospective clinical trial. Laser Surg Med. (2022) 54:1060–70. doi: 10.1002/lsm.23581

  • 162

    Sazgarnia A Shanei A Taheri ART Meibodi NT Eshghi H Attaran N . Therapeutic effects of acoustic cavitation in the presence of gold nanoparticles on a colon tumor model. J Ultrasound Med. (2013) 32:475–83. doi: 10.7863/jum.2013.32.3.475

Summary

Keywords

gynecological malignant tumors, cervical cancer, ovarian cancer, nanotechnology, gold nanoparticles, diagnosis, treatment

Citation

Zhang S, Li T, Jiang D, Shi H, Hou H, Fu Z and Shi X (2025) Gold nanoparticles in the diagnosis and treatment of ovarian and cervical cancers: a comprehensive understanding. Front. Oncol. 15:1664340. doi: 10.3389/fonc.2025.1664340

Received

11 July 2025

Accepted

25 August 2025

Published

12 September 2025

Volume

15 - 2025

Edited by

Violante Di Donato, Unitelma Sapienza University, Italy

Reviewed by

Mutia Kehwalla Aza, The Johns Hopkins University, United States

Zahra Sadat Dastgheib, Shiraz University of Medical Sciences, Iran

Updates

Copyright

*Correspondence: Xiaoyan Shi,

Disclaimer

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Outline

Figures

Cite article

Copy to clipboard


Export citation file


Share article

Article metrics