Cancer has posed a tremendous threat to the health of human beings worldwide, and an increasing number of people die of cancer every year (Siegel et al., 2022). Great efforts have been devoted to developing new therapeutic modalities for cancer treatment (Li et al., 2019a; Chen et al., 2019; Ma et al., 2019; Li L. et al., 2020; Wang et al., 2021; Li et al., 2023a). Phototherapy, including photodynamic and photothermal therapy, utilizes the photogeneration of reactive oxygen species (ROS) or heat to induce cell apoptosis (Zhen et al., 2017; Li et al., 2019b; Li L. et al., 2019; Yang and Chen, 2019; Li et al., 2020; Zheng et al., 2020; Zou et al., 2021a; Wu et al.). Solid tumors usually suffer from hypoxia which is strongly associated with tumor propagation, malignant progression, and resistance to therapy. However, several factors limit the widespread clinical use of photodynamic therapy (PDT), such as O2 shortage induced hypoxia and insufficient tissue penetration depth (Fan et al., 2016; Zhou et al., 2016; Liu et al., 2019; Qi et al., 2022). Therefore, new intelligent photosensitizers should be designed and synthesized to achieve better phototherapeutic efficacy. Apart from cancer therapy, PDT has been universally utilized in a variety of fields, such as plastic and re-constructive surgery. Wu et al. from Shanghai Jiaotong University has summarized the application of PDT in benign pigmented lesion, vascular malformation, inflammatory lesion, etc.
In recent years, great efforts have been devoted to relieving hypoxia, for example, in situ oxygen generation or delivering oxygen to the tumor (Yang et al., 2017; Lin et al., 2018; Shen et al., 2022; Li et al., 2023b; Chen et al., 2023). Representative work by Jianlin Shi is the in situ generation of oxygen, typically transition metal oxides, such as MnO2 in the TME. The degradation of MnO2 not only releases oxygen but also leads to the metabolism of Mn2+ (Fan et al., 2015). Another way is to deliver molecular oxygen to the tumor region, typical of which is the utilization of Food and Drug Agency (FDA) approved perfluorocarbon capable of carrying the oxygen (Cheng et al., 2015; Wang W. et al., 2019). Perfluorocarbon proves to be a safe drug with excellent bio-compatibility. In addition, the fractionated delivery of singlet oxygen by chemical storage is an efficient approach to treatment of hypoxic tumors. In the process, singlet oxygen is usually captured by the moiety, such as pyridione, anthracene with laser irradiation (Zou et al., 2020; Zou et al., 2021b). Then it will be released when the laser is off. Fractionated delivery of singlet is a kind of mild PDT and diminishes the damage of blood vessels, thus contributes to supplying oxygen during blood circulation. Apart from relieving hypoxia, diminishing oxygen consumption with oxygen-independent therapy is considered as another effective way, for example, type I PDT (Ding et al., 2011; Wang Y. et al., 2019; Zhuang et al., 2020). Different from type II PDT, type I PDT is based on the sensitization of photosensitizers to generate superoxide/hydroxyl radicals which may derive from not only molecular oxygen, but also water or hydrogen peroxide. A classic example is the radiosensitization of TiO2 by X-ray leads to the efficient generation of hydroxyl radicals (Zhang et al., 2014). In recent years, photosensitizers with NIR absorbance may also act similarly. In the Research Topic, Cui et al. from Xiangyang Central Hospital synthesized a semiconducting polymer (PDPP) and encapsulated it with hydrophilic PEG-PDPA to enhance the electron transfer for type I PDT. PDPP NPs show high superoxide radical generation ability. Both in vitro and in vivo study demonstrate PDPP NPs with considerably high phototoxicity against human cervical cancer. Apart from hydrophilic PEG, extracellular vesicles (EVs) can also be used as the platform for the delivery of photosensitizers (Tong et al.). Tong et al. from Shandong First Medical University have systematically summarized the passive and active loading strategies of photosensitizers into EVs, the advantages and disadvantages of EV based delivery nanoplatform. According to their statistical analysis, cancer cells (23.6%), stem cells (22.9%), and HEK293 (21.7%) derived EVs were most commonly used in preclinical studies. This may be because researchers are trying to take advantage of the homing and immune escaping properties of EV pararenal cells, such as cancer cells and stem cells (Escude Martinez de Castilla et al., 2021).
Activatable nano-platform for cancer therapy is attracting broad interest (Turan et al., 2016; Hu et al., 2018; Zou D. et al., 2021). Glutathione (GSH) with reductivity exists universally in cancer cells. Designing nanomaterials for depletion of GSH may enhance the therapeutic efficacy of PDT. Tang et al. from Guangdong Medical University prepared a smart nanoplatform for enhanced photo-ferrotherapy against hepatocellular carcinoma. Given that the overexpression of hydrogen sulfide (H2S) in colorectal cancer (CRC), Li et al. from the National Institutes of Health (NIH) developed a novel metal-organic framework (MOF) composed of meso-Tetra (4-carboxyphenyl) porphine (TCPP) and ferric ion (Fe3+) through a facile one-pot process. The MOF is capable of depredating in response to the high content of H2S in tumor microenvironment of CRC.
NIR-II fluorescence imaging benefits from deeper penetration, less tissue scattering and diminished auto-fluorescence (Hong et al., 2017; Tian et al., 2019; Pei et al., 2021). Niu et al. from the First Affiliated Hospital of Fujian Medical University reported a biomineralized hybrid nanodots (CuxMnySz@BSA@ICG, ICG = indocyanine green) for tumor therapy via NIR-II fluorescence for photothermal therapy. CuxMnySz@BSA@ICG converts endogenous hydrogen peroxide (H2O2) into highly active hydroxyl radical (•OH) via Fenton reaction, and effectively produces reactive oxygen species (ROS) after being exposed to 808 nm laser irradiation. This results in eliciting a ROS storm, leading to the regression of tumor.
This Research Topic has attracted extensive interest from researchers who would like to seek new therapeutic methods for better understanding the relationship between the structure and therapeutic efficacy. The knowledge generated here not only benefits the researchers focused on synthetic chemistry and biomaterials but also adds to the understanding of cancer treatment for pre-clinical application. Further investigation should still be continued for cancer phototheranostics.
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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.
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References
1
Chen Q. Hu Q. Dukhovlinova E. Chen G. Ahn S. Wang C. et al (2019). Photothermal therapy promotes tumor infiltration and antitumor activity of CAR T cells. Adv. Mater31 (23), e1900192. 10.1002/adma.201900192
2
Chen Z. Liu Z. Zhang Q. Huang S. Zhang Z. Feng X. et al (2023). Hypoxia-ameliorated photothermal manganese dioxide nanoplatform for reversing doxorubicin resistance. Front. Pharmacol.14, 1133011. 10.3389/fphar.2023.1133011
3
Cheng Y. Cheng H. Jiang C. Qiu X. Wang K. Huan W. et al (2015). Perfluorocarbon nanoparticles enhance reactive oxygen levels and tumour growth inhibition in photodynamic therapy. Nat. Comm.6, 8785. 10.1038/ncomms9785
4
Ding H. Yu H. Dong Y. Tian R. Huang G. Boothman D. et al (2011). Photoactivation switch from type II to type I reactions by electron-rich micelles for improved photodynamic therapy of cancer cells under hypoxia. J. Control Release156 (3), 276–280. 10.1016/j.jconrel.2011.08.019
5
Escude Martinez de Castilla P. Tong L. Huang C. Sofias A. M. Pastorin G. Chen X. et al (2021). Extracellular vesicles as a drug delivery system: A systematic review of preclinical studies. Adv. Drug Deliv. Rev.175, 113801. 10.1016/j.addr.2021.05.011
6
Fan W. Bu W. Shen B. He Q. Cui Z. Liu Y. et al (2015). Intelligent MnO2 nanosheets anchored with upconversion nanoprobes for concurrent pH-/H2O2 -responsive UCL imaging and oxygen-elevated synergetic therapy. Adv. Mat.27, 4155–4161. 10.1002/adma.201405141
7
Fan W. Huang P. Chen X. (2016). Overcoming the Achilles’ heel of photodynamic therapy. Chem. Soc. Rev.45 (23), 6488–6519. 10.1039/c6cs00616g
8
Hong G. Antaris A. L. Dai H. (2017). Near-infrared fluorophores for biomedical imaging. Nat. Biomed. Eng.1, 0010. 10.1038/s41551-016-0010
9
Hu W. Xie M. Zhao H. Tang Y. Yao S. He T. et al (2018). Nitric oxide activatable photosensitizer accompanying extremely elevated two-photon absorption for efficient fluorescence imaging and photodynamic therapy. Chem. Sci.9, 999–1005. 10.1039/c7sc04044j
10
Li J. Cui D. Jiang Y. Huang J. Cheng P. Pu K. , (2019a) Near-Infrared photoactivatable semiconducting polymer nanoblockaders for metastasis-inhibited combination cancer therapy, Adv. Mater31 (46), e1905091. 10.1002/adma.201905091
11
Li J. Huang J. Lyu Y. Huang J. Jiang Y. Xie C. et al (2019b). Photoactivatable organic semiconducting pro-nanoenzymes. J. Am. Chem. Soc.141 (9), 4073–4079. 10.1021/jacs.8b13507
12
Li L. Zou J. Dai Y. Fan W. Niu G. Yang Z. et al (2020a). Burst release of encapsulated annexin A5 in tumours boosts cytotoxic T-cell responses by blocking the phagocytosis of apoptotic cells. Nat. Biomed. Eng.4 (11), 1102–1116. 10.1038/s41551-020-0599-5
13
Li L. Yang Z. Zhu S. He L. Fan W. Tang W. et al (2019c). A rationally designed semiconducting polymer brush for NIR-II imaging-guided light-triggered remote control of CRISPR/Cas9 genome editing. Adv. Mater31, 1901187. 10.1002/adma.201901187
14
Li X. Lovell J. Yoon J. Chen X. (2020b). Clinical development and potential of photothermal and photodynamic therapies for cancer. Nat. Rev. Clin. Oncol.17 (11), 657–674. 10.1038/s41571-020-0410-2
15
Li Z. Zou J. Chen X. (2023a). In response to precision medicine: Current subcellular targeting strategies for cancer therapy. Adv. Mater35, 2209529. 10.1002/adma.202209529
16
Li Z. Zou J. Chen X. (2023b). Response to precision medicine: current sub-cellular targeting strategies for cancer therapy. Adv. Mater, 2209529.
17
Lin T. Zhao X. Zhao S. Yu H. Cao W. Chen W. et al (2018). O2-generating MnO2 nanoparticles for enhanced photodynamic therapy of bladder cancer by ameliorating hypoxia. Theranostics8 (4), 990–1004. 10.7150/thno.22465
18
Liu Z. Xue Y. Wu M. Yang G. Lan M. Zhang W. (2019). Sensitization of hypoxic tumor to photodynamic therapy via oxygen self-supply of fluorinated photosensitizers. Biomacromolecules20 (12), 4563–4573. 10.1021/acs.biomac.9b01368
19
Ma Y. Zhang Y. Li X. Zhao Y. Li M. Jiang W. et al (2019). Near-Infrared II Phototherapy induces deep tissue immunogenic cell death and potentiates cancer immunotherapy. ACS Nano13 (10), 11967–11980. 10.1021/acsnano.9b06040
20
Pei P. Chen Y. Sun C. Fan Y. Yang Y. Liu X. et al (2021). X-ray-activated persistent luminescence nanomaterials for NIR-II imaging. Nat. Nanotechnol.16 (9), 1011–1018. 10.1038/s41565-021-00922-3
21
Qi Y. Wang H. Du A. Liu C. Sun X. Meng X. et al (2022). Engineering multifunctional thylakoid as an oxygen self-supplying photosensitizer for esophageal squamous cell carcinoma-targeted photodynamic therapy. CCS Chem., 1–15. 10.31635/ccschem.022.202202404
22
Shen J. Pan L. Zhang X. Zou Z. Wei B. Chen Y. et al (2022). Delivering singlet oxygen in dark condition with an anthracene-functionalized semiconducting compound for enhanced phototheranostics. Front. Bioeng. Biotechnol.10, 781766. 10.3389/fbioe.2022.781766
23
Siegel L. Miller K. Fuchs H. Jemal A. , (2022). Cancer statistics, 2022, CA CANCER J. Clin.72:7–33. 10.3322/caac.21708
24
Tian R. Zeng Q. Zhu S. Lau J. Chandra S. Ertsey R. et al (2019). Albumin-chaperoned cyanine dye yields superbright NIR-II fluorophore with enhanced pharmacokinetics. Sci. Adv.5, eaaw0672. 10.1126/sciadv.aaw0672
25
Turan I. S. Yildiz D. Turksoy A. Gunaydin G. Akkaya E. U. (2016). A bifunctional photosensitizer for enhanced fractional photodynamic therapy: Singlet oxygen generation in the presence and absence of light. Angew. Chem. Int. Ed.55 (8), 2925–2928. 10.1002/ange.201511345
26
Wang W. Cheng Y. Yu P. Wang H. Zhang Y. Xu H. et al (2019a). Perfluorocarbon regulates the intratumoural environment to enhance hypoxia-based agent efficacy. Nat. Comm.10, 1580. 10.1038/s41467-019-09389-2
27
Wang Y. Liu Y. Sun H. Guo D. (2019b). Type I photodynamic therapy by organic–inorganic hybrid materials: From strategies to applications. Coord. Chem. Rev.395, 46–62. 10.1016/j.ccr.2019.05.016
28
Wang Z. Zhan M. Li W. Chu C. Xing D. Lu S. et al (2021). Photoacoustic cavitation-ignited reactive oxygen species to amplify peroxynitrite burst by photosensitization-free polymeric nanocapsules. Angew. Chem. Int. Ed.60, 4720–4731. 10.1002/anie.202013301
29
Yang G. Xu L. Chao Y. Xu J. Sun X. Wu Y. et al (2017). Hollow MnO2 as a tumor-microenvironmentresponsive biodegradable nano-platform for combination therapy favoring antitumor immune responses. Nat. Comm.8, 902. 10.1038/s41467-017-01050-0
30
Yang Z. Chen X. (2019). Semiconducting perylene diimide nanostructure: Multifunctional phototheranostic nanoplatform. Acc. Chem. Res.52 (5), 1245–1254. 10.1021/acs.accounts.9b00064
31
Zhang H. Shan Y. Dong L. (2014). A comparison of TiO2 and ZnO nanoparticles as photosensitizers in photodynamic therapy for cancer. J. Biomed. Nanotechnol.10 (8), 1450–1457. 10.1166/jbn.2014.1961
32
Zhen Z. Tang W. Wang M. Zhou S. Wang H. Wu Z. et al (2017). Protein nanocage mediated fibroblast-activation protein targeted photoimmunotherapy to enhance cytotoxic T cell infiltration and tumor control. Nano Lett.17 (2), 862–869. 10.1021/acs.nanolett.6b04150
33
Zheng Z. Liu H. Zhai S. Zhang H. Shan G. Kwok R. et al (2020). Highly efficient singlet oxygen generation, two-photon photodynamic therapy and melanoma ablation by rationally designed mitochondria specific near-infrared AIEgens. Chem. Sci.11, 2494–2503. 10.1039/c9sc06441a
34
Zhou Z. Song J. Nie L. Chen X. (2016). Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy. Chem. Soc. Rev.45 (23), 6597–6626. 10.1039/c6cs00271d
35
Zhuang Z. Dai J. Yu M. Li J. Shen P. Hu R. et al (2020). Type I photosensitizers based on phosphindole oxide for photodynamic therapy: Apoptosis and autophagy induced by endoplasmic reticulum stress. Chem. Sci.11, 3405–3417. 10.1039/d0sc00785d
36
Zou D. Zhang A. Chen J. Chen Z. Deng J. Li G. et al (2021c). Designing a lysosome targeting nanomedicine for pH triggered enhanced phototheranostics. Mat. Chem. Front.5, 2694–2701. 10.1039/d0qm01016b
37
Zou J. Li L. Yang Z. Chen X. (2021a). Phototherapy meets immunotherapy, a win-win strategy to fight against cancer. Nanophotonics10 (12), 3229–3245. 10.1515/nanoph-2021-0209
38
Zou J. Li L. Zhu J. Li X. Yang Z. Huang W. et al (2021b). Singlet oxygen “afterglow” therapy with NIR‐II fluorescent molecules. Adv. Mat.33, 2103627. 10.1002/adma.202103627
39
Zou J. Zhu J. Yang Z. Li L. Fan W. He L. et al (2020). A phototheranostic strategy to continuously deliver singlet oxygen in the dark and hypoxic tumor microenvironment. Angew. Chem. Int. Ed.59 (23), 8833–8838. 10.1002/anie.201914384
Summary
Keywords
photosensitizer, theranostics, hypoxia, penetration depth, X-PDT
Citation
Zou J, Zhang F, Fan W, Li L and Yang Z (2023) Editorial: Synthesis of novel photosensitizers for cancer theranostics. Front. Chem. 11:1188243. doi: 10.3389/fchem.2023.1188243
Received
17 March 2023
Accepted
03 July 2023
Published
10 July 2023
Volume
11 - 2023
Edited and reviewed by
Jayachandran Jayakumar, National Tsing Hua University, Taiwan
Updates
Copyright
© 2023 Zou, Zhang, Fan, Li and Yang.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Jianhua Zou, zoujh-93@nus.edu.sg; Fuwu Zhang, fxz174@miami.edu; Wenpei Fan, wenpei.fan@cpu.edu.cn; Ling Li, lingliscu@163.com; Zhen Yang, beijinyz@126.com
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.