The crosstalk between sonodynamic therapy and autophagy in cancer

Abstract

As a noninvasive treatment approach for cancer and other diseases, sonodynamic therapy (SDT) has attracted extensive attention due to the deep penetration of ultrasound, good focusing, and selective irradiation sites. However, intrinsic limitations of traditional sonosensitizers hinder the widespread application of SDT. With the development of nanotechnology, nanoparticles as sonosensitizers or as a vehicle to deliver sonosensitizers have been designed and used to target tissues or tumor cells with high specificity and accuracy. Autophagy is a common metabolic alteration in both normal cells and tumor cells. When autophagy happens, a double-membrane autophagosome with sequestrated intracellular components is delivered and fused with lysosomes for degradation. Recycling these cell materials can promote survival under a variety of stress conditions. Numerous studies have revealed that both apoptosis and autophagy occur after SDT. This review summarizes recent progress in autophagy activation by SDT through multiple mechanisms in tumor therapies, drug resistance, and lipid catabolism. A promising tumor therapy, which combines SDT with autophagy inhibition using a nanoparticle delivering system, is presented and investigated.

1 Introduction

Ultrasound (US) has been widely used for both diagnostics and therapeutics in many fields, such as B-scan ultrasonography, bone repair, diabetic nephropathy, cancer therapy, immunotherapy, vaccination, and drug delivery (Cao et al., 2016; Escoffre et al., 2016; McHale et al., 2016; Padilla et al., 2016). Among these applications, the flexibility of US as an approach for noninvasively eradicating target solid tumors has recently drawn increasing attention (McHale et al., 2016). In cancer therapy, an ideal approach would be to apply a harmless stimulus that could lead to cytotoxic events at the target tumor tissue specifically and accurately. SDT, with its deep tissue penetration and high precision, has a great potential to become an ideal tumor therapy since sonochemical or sonophotochemical reactions, which lead to cytotoxicity under a controlled US irradiation with the help of certain chosen sonosensitizers (Liu et al., 2015). The major limitations of the sonosensitizers used in the SDT include poor delivery accuracy and high toxicity (Pelt et al., 2018). With the development of nanotechnology, nanoparticles (NPs)-based sonosensitizers were designed, which made use of NPs to deliver the sonosensitizers to target tissues or tumor cells with high specificity (Chen et al., 2014; Qian et al., 2016; Feng et al., 2019; Qu et al., 2020). The other problem encountered is that SDT can promote autophagy in tumor cells, which influences the efficiency of SDT. In other words, autophagy can assist tumor cell survival by recycling damaged organelles and misfolded proteins under different stress conditions (Helgason et al., 2013; White et al., 2015; Levy et al., 2017). Researchers have proposed to inhibit the SDT-induced autophagy in order to improve the efficiency of SDT improvement (Chen et al., 2014; Mahalingam et al., 2014; Vogl et al., 2014; Song et al., 2018; Feng et al., 2019; Qu et al., 2020).

In this review, the mechanism and sonosensitizers of SDT are firstly summarized. Next, the recent progress in tumor therapies with emphasis on SDT is introduced. The relationship between SDT and autophagy in tumor therapies and other metabolic pathways is also reviewed. To better present this study, an introduction to autophagy is also detailed. Finally, a promising tumor therapy, which combines SDT with autophagy inhibition using a nanoparticle delivering system, is presented and investigated.

2 Sonodynamic therapy

Before the use of US for therapeutic purposes, the application of light was considered an option for non-invasive therapy, which was referred to as photodynamic therapy (PDT). PDT is the predecessor of SDT. PDT involves three constituent elements: a light source, a photosensitizer, and the local tissue oxygen. Reactive oxygen species (ROS) are formed in the tumor cells and tissues with porphyrins upon irradiation with light (Rkein and Ozog, 2014). PDT can interfere with cytokine-mediated responses in tumor progression and metastasis and play a pivot role (Kaleta-Richter et al., 2019). However, since the light has only a limited penetration depth, PDT cannot be effectively applied to deep-seated tumors (Huang, 2005). At the same time, PDT highly relies on the ability of specific photosensitizing agents to concentrate in tumor cells (Kessel and Oleinick, 2009). Therefore, lacking a suitable photosensitizing agent with high efficiency, good sensitivity, wide applicability, and low toxicity severely constrain the research on PDT. In addition, the study showed that autophagy induced by PDT treatment could act as a mode of cell death after PDT (Buytaert et al., 2006; Kessel et al., 2006; Xue et al., 2007; Buytaert et al., 2008). However as a double-edged sword, autophagy can also promote tumor cell survival by compartmentalizing and recycling damaged tumor cell components after PDT, which significantly reduces the sensitivity and efficiency of PDT (Kessel et al., 2006; Kessel and Oleinick, 2009; Kaleta-Richter et al., 2019).

Based on PDT, SDT is gradually developed and optimized. The SDT is a new non-invasive tumor treatment method raised by Yumita et al. (1989) in 1989. When conducting research on PDT, they observed that some hematoporphyrin derivatives could also induce cell death under US irradiation (Yumita et al., 1989). It was then found that combined with US irradiation, some hematoporphyrin derivatives could act as sonosensitizers for tumor therapy, and this therapy was referred to as SDT. Research shows that most photosensitizers are sonosensitizers. Both PDT and SDT require the use of photosensitizer/sonosensitizers to trigger intracellular oxygen generation ROS to kill tumor cells. The SDT relies on the US and sonosensitizers present in the tumor tissue, with specific frequency and intensity, US irradiates the tumor site in deep tissue for a particular time, a lethal sono-damage such as necrosis and cell apoptosis by both mechanical stress and chemical reactions is caused and finally kills the tumor cells with high specificity and accuracy (Wang et al., 2013b; Parzych and Klionsky, 2014). Due to the deep penetration of US, SDT overcomes the major limitation of PDT. The SDT method is superior to the PDT method with deeper tissue penetration, higher precision, fewer side effects, and better patient compliance (Wang et al., 2013b; Pan et al., 2018b). The cytotoxic mechanisms of SDT in tumor treatment mainly include ultrasonic cavitation effect, singlet oxygen mechanism, mechanical damages, ultrasonic heating effect, apoptosis theory, and comprehensive effects of the mentioned mechanisms (Liu et al., 2015; Rengeng et al., 2017).

The major limitations of the sonosensitizers used in the SDT include poor delivery accuracy and high toxicity (Pelt et al., 2018). With the development of nanotechnology, nanoparticle-based sonosensitizers were designed, which make use of NPs to deliver the sonosensitizers to target tissues with high specificity (Chen et al., 2014; Qian et al., 2016; Feng et al., 2019; Qu et al., 2020). The other problem encountered is that SDT can promote autophagy in tumor cells, which inhibits the efficiency of SDT. It is because autophagy can assist tumor cell survival by recycling damaged organelles and misfolded proteins under different stress conditions (Helgason et al., 2013; White et al., 2015; Levy et al., 2017). Recently, the effect of autophagy induced by SDT in tumor treatment has drawn increasing attention (Wang et al., 2013b). Researchers have proposed to inhibit the SDT-induced autophagy in order to improve the efficiency of SDT (Chen et al., 2014; Mahalingam et al., 2014; Vogl et al., 2014; Song et al., 2018; Feng et al., 2019; Qu et al., 2020).

2.1 Mechanism of sonodynamic therapy

The mechanisms of SDT include the generation of ROS, US mechanical damage, and thermal destruction. Figure 1 depicts the possible mechanisms of SDT.

FIGURE 1

2.1.1 Generation of reactive oxygen species

ROS generation is the most widely accepted mechanism of SDT, and this theory focuses on the cancer cell apoptosis caused by ROS production induced by cavitation and sonosensitizers (Nora Frulio et al., 2010). Under the irradiation of US, sonosensitizers can be activated from the ground state to the excited state to generate ROS, including singlet oxygen and hydroxyl radicals. Acoustic cavitation plays an important role in activating sonosensitizers to generate ROS during the interaction of US with an aqueous environment. The cavitation process involves the nucleation, growth, and implosive collapse of gas-filled bubbles under certain US conditions. Cavitation can be classified into stable cavitation and inertial cavitation based on its nature. In stable cavitation, gas-filled bubbles oscillate with the surrounding liquid to create a mixing of the surrounding media. In inertial cavitation, the gas-filled bubbles grow to a near resonance size and expand before collapsing violently (Suslick, 1990). A considerable amount of energy is released in the implosion, leading to very high temperature (up to 10,000 K) and pressure (up to 81 MPa) in the microenvironment (Cavalli et al., 2018). The resultant extreme temperature and pressure may act as sonochemical reactors and lead to tumor cell necrosis (Misik and Riesz, 2000).

Two kinds of ROS can be generated by different reactions. The sonosensitizers at excited state can react directly with adjacent oxygen to turn hydrogen atoms to free radicals. Alternatively, the energy released by the sonosensitizers from the excited state to the ground state can be absorbed by the adjacent oxygen to produce high active singlet oxygens (¹O₂), which account for the primary SDT toxicity. In addition, sonoluminescence, a phenomenon referring to that light is generated when a solution is irradiated with US, is identified as another significant mechanism in generating ROS (Suslick et al., 1990; Yin et al., 2016). The sonoluminescent light can motivate the energy-matching photoactive sonosensitizers to a short-lived singlet state, which would lead to photochemical reactions (Didenko et al., 2000; Yin et al., 2016). Pyrolysis can be another possible mechanism for generating ROS (Danno et al., 2008). The extreme temperature and pressure during the implosion of gas-filled bubbles could generate free radicals in the following two ways: direct sonosensitizer breakdown or sonosensitizer reactions with H⁺ or OH⁻ produced by the thermolysis of water (Danno et al., 2008). Irreversible damage to targeted tumor cells, including cell membrane damage, DNA fragmentation, and mitochondrial membrane potential disturbance, can be induced by the high concentration of ROS (Kwon et al., 2019). Studies have shown that ROS activate autophagy through a variety of pathways to mediate cell survival or death. Especially, it was found that ROS induced by SDT triggered autophagy in a mitochondria-dependent minner (Qu et al., 2020).

2.1.2 Ultrasound mechanical damages

The main factors causing US mechanical damage are cavitation effects and US radiation force (Yuan et al., 2015). It was reported that the mechanical pressure from US could lead to cell necrosis (Wang et al., 2003; Hiraoka et al., 2006). During the rapid collapsing of gas-filled bubbles under US irradiation, a considerable amount of energy is released to produce extreme temperature and pressure (Hiraoka et al., 2006). High shear stress and strong shock waves are generated, and they enhance the physical damage to cytomembranes, which ultimately lead to mechanical damage and tumor cell necrosis (Forbes et al., 2011).

2.1.3 Thermal destruction

The increase of tissue temperature through absorption and transformation of the US mechanical energy can also lead to tumor cell necrosis (Xiong et al., 2020). For example, under the irradiation of appropriate US, the sonosensitizer mesoporous silica NPs can cause hyperthermia to kill tumor cells. Due to the high penetration and high energy concentration capabilities of US, SDT can cause thermal destruction to deep-seated tumors (Xiong et al., 2020).

2.2 Sonosensitizers with nanoparticle delivery system

In SDT, the sonosensitizers can be classified into two groups: organic and inorganic (Table 1). The organic sonosensitizers have high SDT efficiency but with poor pharmacokinetics, skin sensitivity, low stability, and poor SDT efficiency. The inorganic sonosensitizers have superior physical and chemical properties and can be multifunctional. However, the poor SDT efficiency and potential biosafety problems are the main challenges for inorganic sonosensitizers (Liang et al., 2020a).

Currently, there are many limitations of sonosensitizers, which significantly influence the efficiency and sensitivity of SDT. The major challenges are the low drug delivery efficiency and limited generation of ROS (Hou et al., 2020). To make SDT practically applicable, thanks to the fast developing nanotechnology, nanoparticles-based sonosensitizers are introduced, which make use of nanoparticles to deliver the sonosensitizers to target tissues or tumor cells with high specificity and accuracy, and in the end, improve the outcomes of SDT (Pan et al., 2018b). Nano-sonosensitizers can be divided into two groups: nanoparticle as intrinsic sonosensitizer (TiO₂, Ag/Pt, Si NPs, and polyhydroxy fullerene) and nanoparticle-assisted sonosensitizer (self-assembled, conjugated, embedded, or encapsulated) (Harada et al., 2011; Pan et al., 2018b; An et al., 2020a). Nano-sonosensitizers were summarized in Table 2 of Plenty of previous research has been conducted on NP-mediated SDT. As a typical semiconductor, TiO₂ has drawn much attention, and TiO₂ NPs are shown to have positive anti-tumor effects both in vitro and in vivo under US irradiation (Harada et al., 2011). Harada et al. (2011) reported that compared to 1 MHz of US irradiation alone, combined US irradiation of mice injected with TiO₂ had a significant anti-tumor effect. However, the bio-distributions of traditional TiO₂ NPs are hard to manipulate, and the acute and long-run toxicity is unsatisfactory (Chen et al., 2014). Therefore, searching for an efficient and sensitive sonosensitizer is urgently needed.

Organic NP carriers for sonosensitizers are superior in high aqueous solubility, good bio-compatibility, satisfactory targeting specificity, and easy bio-degradation (Qian et al., 2016). Chen et al. (2017b) applied mitochondria targeting liposomes to carry hydrophobic sonosensitizer of hematoporphyrin monomethyl ether, which were released from the liposomes under US, and remarkably prevented the aggregation of sonosensitizers. Canaparo et al. (2013) reported that NPs delivered the sonosensitizers with high accuracy and enhanced the efficiency of carried sonosensitizers. Rui et al. (Hou et al., 2020) designed a sonosensitizer drug delivery system for rose bengal microbubbles. This drug delivery system was shown to have high drug loading content and good US imaging properties. Under US irradiation, the locations and sizes of the tumors were observed. More importantly, the rose bengal microbubbles were converted into rose bengal NPs through sonoporation effects in situ with US irradiation, which could bring many favorable effects, including high drug accumulation, and promoted generation efficiency of ROS. The high drug accumulation at the tumor site reduced the side effects, and the improved SDT efficiency showed great potential for cancer therapies.

The multifunctional NP systems with diagnostic and therapeutic functions have recently gained increasing attention in precision nanomedicine (Huang et al., 2018; Li et al., 2019). In the NP system investigated by Li et al. (2016a), the hydrophilic biodegradable polymeric NPs carried both sonosensitizer and a magnetic resonance contrast agent (Li et al., 2019). In order to target the tumor tissues with higher specificity and accuracy, the tumor-homing and penetrating peptide-F3 was used to decorate the surfaces of NPs. This designed F3 decorated poly lactic-co-glycolic acid NP showed a significantly higher tumor tissue concentration than non-targeted NP. More importantly, under satisfactory drug safety, the apoptosis caused by SDT with the designed multifunctional NP system was promoted. The results indicated a potential for further investigations and even clinical trials.

Huang et al (2018) carried out investigations on the combination of SDT with NP-assisted sonosensitizers under the guidance of photoacoustic imaging, and this novel therapy was expected to eradicate tumor cells accurately. The designed NP-assisted sonosensitizer had a core-shell structure and was based on poly lactic-co-glycolic acid. The core was constructed by integrating melanin NPs for photoacoustic imaging, and the hematoporphyrin monomethyl ether was used to build the shell to enhance photoacoustic imaging-guided SDT. Finally, tumor-targeting ligand folate was attached. The designed NP-assisted sonosensitizer had the following functions: high photoacoustic imaging contrast enhancement capability, accurate delivery of melanin NPs to target tumor tissues, and enhanced SDT performance. Both in vitro and in vivo experiments demonstrated the selective cytotoxicity effects of ROS induced by SDT on tumor cells with the assistance of NP-assisted sonosensitizer, which can promote the eradication of tumor tissues. Meanwhile, the toxicity of the designed NP-assisted sonosensitizer was evaluated, and this sonosensitizer was found to possess high biosafety.

Xu et al. (2020b) synthesized mesoporous silica NPs, and the NPs were loaded with doxorubicin and chlorin e6 as the sonosensitizer. Both in vitro and in vivo experiments were conducted to evaluate the anti-tumor effect of this NP-assisted sonosensitizer under SDT. The NPs were in the shapes of spheres with uniform sizes. The mesoporous structure led to high drug loading and delivery efficiency. On xenograft tumor-bearing mice, under US irradiation, the synthesized NP-assisted sonosensitizer showed a higher tumor suppression effect than doxorubicin combined with chlorin e6 or doxorubicin alone. The results suggested a potential for solid tumor therapy.

Zhang et al. (2019b) designed a mitochondria-targeted and US-activated NP delivery system for enhanced deep-penetration SDT. The built sonosensitizer IR780-based NPs showed effective surface-to-core diffusion in vitro and in vivo. With the guidance of US, the acoustic droplet vaporization effect significantly assisted the conveyance of IR780-NPs from the circulatory system to tumor tissues, and the acoustic wave force increased the penetration depth at the same time. Furthermore, the mitochondrial targeting capability of IR780-NPs improved the delivery accuracy. Following the mitochondrial targeting, the overproduction of ROS rendered cancer cells more susceptible to ROS-induced apoptosis. Meanwhile, IR780-NPs helped with photoacoustic and fluorescence imaging, which provided SDT guidance and monitoring potential.

2.3 Sonodynamic therapy combined with other therapy

Because of the advantages of SDT, it is an effective method for the treatment of a variety of diseases. Due to the complicated tumor microenvironment, many researchers have integrated SDT with other cancer treatment methods to achieve tumor eradication more effectively (Wan et al., 2016b). SDT can be applied as an adjunctive method to either chemotherapy, PDT, hyperthermotherapy, gas therapy, chemodynamic therapy, immunotherapy, or other therapies (Table 3) (Wan et al., 2016b; Liang et al., 2020a). Recent research suggested that favorable synergistic effects against tumor development and metastasis were achieved in vitro and in vivo when SDT was combined with other tumor therapies (Kondo and Kano, 1987; Gao et al., 2010; Wang et al., 2015b; Liang et al., 2020a).

2.3.1 Sonodynamic therapy with chemotherapy

As one of the commonly adopted clinical therapies against cancer, chemotherapy applies chemotherapeutic drugs with high toxicity to tumor cells. However, severe systemic side effects caused by chemotherapy have always been the major challenge for this tumor therapy. It is suggested that combining chemotherapy with SDT can lead to significantly improved synergistic therapeutic effects with reduced systemic toxicity (Shen et al., 2015; Shi et al., 2015; Nesbitt et al., 2018; Logan et al., 2019; Liang et al., 2020a; Xu et al., 2020b). Chemotherapy often leads to multidrug resistance, which can cause tumor recurrence and metastasis. Combining SDT with chemotherapy has shown great advantages in overcoming drug resistance owing to controlling the release of drugs and increasing cell membrane permeability (Wan et al., 2016a; Chen et al., 2017a; Liu et al., 2017; Li et al., 2018; Liang et al., 2020b; Guan et al., 2022). Moreover, SDT was found to promote cancer cells’ drug sensitivity by improving cellular internalization of chemotherapeutic drugs, activating the mitochondria-caspase signaling pathway, and down-regulating the expression of ATP-binding cassette transporters (Ding et al., 2017; Xu et al., 2020a; Ren et al., 2022). These functions enhanced the cytotoxicity of chemotherapeutic factors and therefore contributed to the promoted therapeutic efficiency (An et al., 2020a; Zhang et al., 2021b; Cao et al., 2021; Zhang et al., 2021c).

2.3.2 Sonodynamic therapy with photodynamic therapy

SDT can also be combined with photodynamic therapy, named sono-photodynamic therapy (SPDT). SPDT could enhance intracellular ROS generation, severe mitochondria damage, cell migration inhibition, nuclear condensation, cell membrane permeability, and significantly trigger cell apoptosis (Wang et al., 2013a; Li et al., 2014a; Li et al., 2014b; Wang et al., 2015a; Liu et al., 2016; Atmaca et al., 2021). Nene and Nyokong (2021) designed a nanoplatform in which phthalocyanines (Pcs) were conjugated to nitrogen (NGQDs) and nitrogen-sulfur (NSGQDs) graphene quantum dots. The nanoparticles were irradiated with light for photodynamic therapy (PDT), ultrasound for sonodynamic therapy, and the combination of both in photo-sonodynamic therapy (PSDT). They found that only ¹O₂ was detected for PDT treatment. In contrast, both the ¹O₂ and ^•OH radicals were evident after SDT and PSDT treatments, and the combination therapy showed improved ROS generation efficacy compared to the monotherapies (Nene and Nyokong, 2021). Aksel et al. (2021) found that malondialdehyde (MDA) levels were increased while superoxide dismutase activity (SOD), catalase (CAT), and glutathione (GSH) levels were decreased after TiO₂-mediated SPDT (Aksel et al., 2021).

2.3.3 Sonodynamic therapy with gas therapy

Gas therapy has attracted much attention as a novel “green” cancer treatment strategy in recent years (Chen et al., 2019). To date, several gases, such as nitrogen (N₂), and nitric oxide (NO), carbon oxide (CO), carbon dioxide (CO₂), have been involved in these therapeutic approaches (Chen et al., 2019). When SDT is combined with gas therapy for tumor treatment, the US triggers gas donors to release and produce highly toxic products or change the disease condition to promote the tumor suppression effects (An et al., 2020b; Cheng et al., 2022; Zhu et al., 2022; Zuo et al., 2022). The generated gas bubbles could be used as a powerful US contrast agent that greatly enhances the US contrast to guide cancer therapy. Some nanoplatforms, such as Lip-AIPH, Au NR-mSiO2/AIPH, OCN-PEG-(Ce6-Gd³⁺)/BNN6, and HMME/MCC-HA, have been explored, which integrated coordinated functions of diagnostics and therapy (Feng et al., 2018; Lin et al., 2019; Zheng et al., 2021b; Ye et al., 2021).

2.3.4 Sonodynamic therapy with immunotherapy

As a promising therapeutic modality for cancer treatment, immunotherapy, which stimulates the host tumor-specific innate and acquires systemic immune responses to attack cancer cells, is different from other traditional cancer therapies that directly target malignant cells (Li et al., 2021; Liang et al., 2021). Furthermore, immunotherapy can ablate localized tumors, inhibit distant tumors, and suppress tumor metastasis. After immunotherapy, the host can form long-term immune memory to prevent tumor recurrence (Li et al., 2021; Liang et al., 2021). SDT can motivate immune responses by eliciting ICD (immunogenic cell death) induced by the production of cytotoxic ROSs to suppress tumor growth and prevent tumor recurrence effectively (Li et al., 2020; Cheng et al., 2021; Yin et al., 2021). PFCE@THPP_pf-COPs designed by Yang et al. (2022) can attenuate tumor hypoxia and suppress tumor growth by inducing ICD of cancer cells. After combining with anti-CD47 immunotherapy, this synergistic treatment exhibited potent protective memory antitumor immunity to prevent tumor recurrence (Yang et al., 2022). Some smart SDT platforms that induced potent antitumor immune responses were designed in recent years, such as MON-PpIX-LA-CO₂ (Yin et al., 2021), DYSP-C34 (Wang et al., 2021a), TiO₂@CaP (Tan et al., 2021), membrane-coated Fe-PDAP/Ce6 (Jiang et al., 2022), Zn-TCPP/CpG (Zhu et al., 2020b), and so on. Immunotherapy has great potential to be combined with SDT to achieve more effective cancer treatments. Yue et al. (2019) combined noninvasive SDT with checkpoint blockade immunotherapy by the nanosonosensitizers HMME/R837@Lip to induce an anti-tumour response, and this combination arrested primary tumor progression and prevented lung metastasis. Other nanocarriers combining SDT with immunotherapy were also developed, such as TIR@FITC-Nrf2-siRNA (Wan et al., 2021), TiO₂-Ce6-CpG (Lin et al., 2021), PEG-CDM-aPD-L1/Ce6 (Huang et al., 2021) and this combinatorial tumor therapeutics can robust anti-cancer immunity and long-term immune memory (Table 3).

2.3.5 Sonodynamic therapy with other therapies

Materials with high absorbance in the NIR-II region could be applied in photo-induced cancer therapy. The photothermal effect could prolong blood circulation and improve the O₂ supply, promoting ROS generation (Wang et al., 2021b; Geng et al., 2021; Li et al., 2022). The thermal effect in photothermal therapy can boost the efficiency of SDT and achieve synergistically enhanced therapeutic purposes (Zhang et al., 2021a; Kayani et al., 2021). At the same time, researchers have found that SDT can induce protective autophagy, which significantly reduces the efficiency of SDT, making it possible to combine SDT with autophagy to enhance the therapeutic efficacy (Feng et al., 2019; Liang et al., 2020a; Qu et al., 2020; Zhou et al., 2021).

3 Autophagy

3.1 Overview of autophagy pathway

Autophagy can be divided into three types according to the role of lysosomes, including macroautophagy, microautophagy, and chaperone-mediated autophagy. Macroautophagy (referred to autophagy) is a process in which cells can form double-membraned autophagic vesicles named autophagosome that sequesters damaged organelles and misfold proteins and fuse with lysosome to form autolysosome for degradation (Figure 2) (Antonioli et al., 2017; Zhao et al., 2021). Microautophagy refers to a process in which misfolded proteins or damaged organelles are directly wrapped by lysosomal traps without forming autophagosomes. Molecular chaperone mediated autophagy refers to the process in which substrate protein is bound to lamp-2A receptor on lysosome by molecular chaperone such as HSP70, mediating its degradation (Bandyopachyay and Cuervo, 2008). Therefore, the autophagy process discussed in this paper is macroautophagy, referred to as autophagy.

FIGURE 2

3.1.1 Initiation

Induction of autophagosome formation is regulated by the Unc-51-like kinase (ULK) complex, which is made up of a ULK family kinase (ULK1 and ULK2), autophagy-related gene 13 (ATG13), RB1-inducible coiled-coil 1 (RB1CC1/FIP200) and ATG101 (Hara et al., 2008; Chan, 2009; Zachari and Ganley, 2017).

3.1.2 Nucleation, elongation, and maturation

The phosphatidylinositol 3-phosphate kinase (PI3K) complex consists of VPS34, BECN 1, ATG14L, and p150. Next, NRBF2 is recruited to the putative site of autophagosome formation (Matsunaga et al., 2009; Lu et al., 2014). Phosphatidylinositol (PI) in isolation membrane or omegasome is phosphorylated by the PI3K complex to produce phosphatidylinositol 3-phosphate (PtdIns3P), which recruits multiple PtdIns3P-binding proteins to regulate autophagosome formation. ATG12 conjugation system and LC3 conjugation system are involved in elongation. The ATG12-conjugation system includes ATG12, ATG7, ATG10, ATG5, and ATG16L. The LC3-conjugation system includes ProLC3, ATG4, LC3-I, ATG7, ATG3, and LC3-II (LC3-I/PE). The ATG9A/ATG2-WIPI1/2 trafficking system consisting of ATG9A, ATG2, and WIPI1/2 is also involved in autophagosome precursor formation.

3.1.3 Fusion

The fusion of autophagosomes with functional endolysosomal compartments (early endosomes, late endosomes, and lysosomes) is required for autophagosome maturation, which is regulated by RABs, tethers (HOPS), and the SNARE complex (Itakura et al., 2012; Jiang et al., 2014; Tsuboyama et al., 2016; Shen et al., 2021).

3.1.4 Degradation and recirculation of autophagosomal contents

When autophagosome fuses with lysosomes to form autolysosome, autophagic cargo such as misfolded protein and damaged organelles are degraded by lysosomal hydrolases as well as the inner membrane of the autophagosome is degraded into amino acids or peptides for recycling by cells (Mony et al., 2016; Yim and Mizushima, 2020).

3.2 Relationships between autophagy and tumor

Research has shown that the occurrence and development of tumors are closely related to autophagy. Autophagy is deemed an evolutionarily conserved catabolic process in mammalian cells (Glick et al., 2010; Amaravadi et al., 2019). In the autophagy process, a double-membrane autophagosome with a sequestrated intracellular component is delivered and fused with lysosomes for degradation (Parzych and Klionsky, 2014). Recycling these materials can provide energy for the survival of cells under a variety of stress conditions (Glick et al., 2010; White et al., 2015; Kocaturk et al., 2019). The protein aggregates and damaged organelles are also removed to ensure cell homeostasis and quality control (Glick et al., 2010; Kocaturk et al., 2019). Autophagy regulates various physiological functions such as stress resistance, cell death determination, and tissue remodeling. For human cancers, large-scale genomic analysis reveals that it is uncommon to lose or mutate core autophagy genes (Amaravadi et al., 2016). However, oncogenic events that activate autophagy and lysosome biogenesis are identified (Amaravadi et al., 2016). In addition, autophagy can promote cellular senescence and cell surface antigen presentation, which prevents genome instability and necrosis and finally prevents cancer (Glick et al., 2010). Autophagy impacts the interaction between the tumor and the host by assisting stress adaption and eliminating activation of adaptive immune responses. In addition, autophagy helps the crosstalk between the tumor and the stroma, which assists tumor growth under different stress conditions. Therefore, the factors influencing autophagy in cancer include microenvironment stress, starvation level, and the immune system (Amaravadi et al., 2016).

The dichotomous role of autophagy in tumor cells is elaborated in detail. On the one hand, in normal cells, the basal level of autophagy is crucial in ensuring protein quality control by removing misfolded proteins and preventing the accumulation of damaged DNA from maintaining genetic stability. As a result, the autophagy process can suppress the formation of tumor cells. At the early stage some tumors can undergo autophagic cell death (ACD) through the induction of autophagy by some anticancer drugs, in which progress autophagy plays a pro-death role (Amaravadi et al., 2016). On the other hand, autophagy can help tumor cells adapt to diverse adverse environments by providing nutrients and removing cytotoxic substances under stress, thus assisting tumor cell survival. In these circumstances, autophagy plays a pivotal cytoprotective role in promoting malignant tumors’ proliferation, invasion, and metastasis (White et al., 2015). In brief, autophagy acts as a double-edged sword (can have both pro-survival e and pro-death effects) in tumor occurrence, development, and metastasis (Helgason et al., 2013; Levy et al., 2017; Yun and Lee, 2018; Amaravadi et al., 2019).

4 The crosstalk of sonodynamic therapy and autophagy

4.1 Sonodynamic therapy induced autophagy

SDT triggers autophagy (or macroautophagy), which can be divided into two conditions in cancer therapy and lipid metabolism, as summarized in Figure 3. SDT-induced autophagy represents a double-edged sword, and a combination SDT with autophagy inhibition/activation strategies is summarized in Table 4.

FIGURE 3

4.1.1 In cancer therapy

The ultimate target of all anti-tumor therapies is to kill the tumor cells effectively and specifically. Cell death is classified into three types: apoptosis, autophagy, and necrosis (Kitanaka and Kuchino, 1999). Up to now, the major method in anti-tumor therapy is to induce apoptosis. However, tumor cells can escape from apoptosis with multiple pathways triggered by the anti-tumor treatments, among which autophagy is a novel cellular response and is attracting increasing attention (Hsin et al., 2011). Autophagy protects tumor cells from various stimuli, including amino acid deficiency, hypoxia, DNA and mitochondrial damage, and oxidative stress (Amaravadi et al., 2016). With SDT, the tumor cells suffer from various environmental stresses, and therefore autophagy is promoted to assist the tumor cell survival. As a result, the efficiency of SDT is significantly reduced. Many researchers have carried out investigations on SDT-induced autophagy in different tumor cells.

Su et al. (2015) investigated the interplay between apoptosis and autophagy induced by SDT in leukemia K562 cells. Under the protoporphyrin IX (PpIX)-mediated SDT, with the techniques of morphological observation and biochemical analysis, the mitochondrial-dependent apoptosis was noted. At the same time, SDT was observed to promote Autophagy in K562 cells and caused an increase in EGFP-LC3 puncta cells, conversion of LC3 II/I, formation of autophagosome, and co-localization between LC3 and LAMP2 (a lysosome marker). It was proposed that the SDT-induced autophagy is a cytoprotective mechanism because the autophagy inhibitor 3-MA or bafilomycin A1 was shown to suppress autophagy and enhance the SDT-induced apoptosis and necrosis. Experimental data suggested that the ROS caused by PpIX-SDT treatment may play an important role in inducing autophagy. Wang et al. (2013b) investigated the potential inductions of autophagy. Many signaling pathways are involved in the SDT-induced autophagy, such as those related to the control of mitochondria damage and ROS generation. Mitochondria can be a source of ROS and a target of oxidative damage during oxidation stress. In the experiments, the generation of ROS after SDT diffuses the whole cells, including mitochondria, and the accumulated ROS significantly affects the normal functions of the mitochondria. The damaged mitochondria co-localized rapidly with the autophagosome marker, which suggested that mitochondria damage can be one of the triggers for the induction of autophagy. In addition, ROS was also found to be involved in SDT-induced autophagy. Song et al. (2018) proposed the PINK1/Parkin-dependent signaling pathway to initiate mitophagy and autophagy in the human breast adenocarcinoma cell line MCF-7 cells subjected to SDT. The 5-aminolevulinic acid was used as the sonosensitizer. Excessive productions of ROS caused by SDT, together with the PINK1/Parkin-dependent signaling pathway, acted together to initiate mitophagy. The initiated mitophagy and autophagy helped protect the tumor cells against SDT-induced cell death. Qu et al. (2020) designed an “all-in-one” nanosensitizer platform that incorporated Ce6 and HCQ into angiopep-2 peptide-modified liposomes named ACHL. They found that SDT triggered mitophagy dependent on MAPK/p38 activation, which attenuated apoptosis in glioblastoma cells.

It is worth noting that SDT can enhance chemotherapy sensitivity and reverse drug resistance in tumor cells. At the same time, important clues has been emerged that autophagy promotes tumor drug resistance by involves the changes of apoptotic signals (Chang and Zou, 2020). The inhibition of Hedgehog (Hh) signaling pathway induces autophagy in BCR-ABL+ CML cells. Simultaneously inhibiting the Hh pathway and autophagy overcome CML drug resistance (Zeng et al., 2015). Many studies have shown that the addition of inhibitors of the PI3K/AKT/mTOR pathway can effectively enhance tumor therapy (Chang et al., 2013; Rangwala et al., 2014; Zeng et al., 2015). Wu et al. (2018) found that autophagy was induced in paclitaxel-resistant PC-3 cells after SDT treatment. A possible mechanism for promoting autophagy in paclitaxel-resistant PC-3 cells after SDT was the endoplasmic reticulum stress-mediated PI3K/AKT/mTOR signaling pathway. In the experiments, the observation of autophagy was realized by TEM and fluorescence microscopy. After SDT, the inhibition of PI3K/AKT/mTOR signaling pathway by endoplasmic reticulum stress-induced autophagy and autophagy reduced endoplasmic reticulum stress by eliminating the elimination of misfolded proteins and reactive oxygen species. It was further found that autophagy inhibition promoted endoplasmic reticulum stress, therefore down-regulating the PI3K/AKT/mTOR signaling pathway and finally leading to cell death (Wu et al., 2018).

4.2 Combining autophagy inhibition with sonodynamic therapy in cancer therapy

Considering the unfavorable effects of autophagy induced by SDT, many researchers suggested that the combination of SDT with autophagy inhibition can improve the efficiency of tumor therapy (Wang et al., 2010a). The role of autophagy in SDT-induced cytotoxicity in S180 cells was investigated by Wang et al., and an autophagy inhibitor study was performed. Through ample experiments, the autophagy inhibitors significantly promoted the SDT-induced cell death. Specifically, autophagy can participate in SDT-induced cell death, and the inhibition of autophagy at an early stage can promote the tumor treatment efficiency of SDT by the inducted apoptosis and necrosis. Autophagy was detected in the S180 cells treated with SDT under TEM. Double membrane-enclosed vacuoles containing damaged cellular components were observed with TEM. The autophagosomes and autolysosomes involved in this process were further confirmed by the immunofluorescence method. Western blot analysis showed that after SDT, autophagy flux happened in the early stage of cell damage. Kessel and Oleinick raised a similar point that within 1 hour following PDT, the PDT-induced autophagy can be detected. The results showed that with the application of autophagy inhibitors 3-methyladenine or Bafilomycin A1, after 1 hour following SDT, the loss of mitochondria membrane potential greatly increased, and therefore inhibiting autophagy can accelerate SDT induced cell death (Kessel and Oleinick, 2009).

Su et al. (2015) reported that intensified autophagy in human chronic myelogenous leukemia K562 cells was induced by protoporphyrin IX (PpIX) mediated SDT, and the induced autophagy was related to the up-regulation of Beclin-1 and the autophagic vacuoles observed in the SDT treated K562 cells. In the experiments, transfection of Beclin-1 shRNA inhibited the conversion of LC3 II/I and autophagic vacuoles significantly, which showed that autophagy was inhibited due to shRNA caused down-regulating of Beclin-1. In addition, compared with SDT only, the combined treatment with Beclin-1 shRNA led to more severe cytotoxicity. It was, therefore, demonstrated that SDT promoted autophagy of K562 cells significantly, autophagy might exert a self-protective effect against sonodamage for K562 cells, and finally, autophagy inhibition promoted cell apoptosis induced by SDT effectively.

The promising role of autophagy for drug development in cancer treatment was discussed. The state-of-art autophagy targeting methods and the potential role of autophagy in tumor immunity were thoroughly studied and reported. Autophagy suppressed tumor initiation but promoted advanced tumor growth. It was further found that autophagy inhibition could be sensitive and effective in advanced cancer therapy (Tanida, 2011). A variety of autophagy inhibitors in clinical trials and laboratory research were discussed, among which hydroxychloroquine (HCQ) treatment was found to be effective in cancer treatment (Shi et al., 2017). The combination of HCQ with other chemicals as the autophagy inhibitor for cancer therapy was also discussed (Goldberg et al., 2012; Cook et al., 2014; Mahalingam et al., 2014; Rangwala et al., 2014; Rosenfeld et al., 2014; Vogl et al., 2014). To conclude, the autophagy inhibitor plays a promising role in tumor treatment. Autophagy inhibitors were summarized in Table 5. Still, research on a suitable autophagy inhibitor with superior targeting, high efficiency, good sensitivity, and low toxicity is further needed. The initiation of autophagy by protoporphyrin IX (PpIX) mediated SDT in murine leukemia L1210 cells was examined by Wang et al. (2013b) Experiments showed that autophagy was protective for tumor cells after SDT and therefore impairment of autophagy can enhance the anti-tumor effect. Experimental data suggested that autophagy inhibition accelerated apoptosis and necrosis of SDT-treated tumor cells. A treatment combining autophagy inhibitors with SDT promotes tumor cell death and will be a promising method for cancer therapy.

Based on the above literature review, it is clearly identified that both SDT and autophagy inhibition has great potential in tumor therapy. To encounter the limitations of traditional sonosensitizers, the nanoparticles-based sonosensitizers, which make use of nanoparticles to deliver the sonosensitizers to target tissues or tumor cells, were introduced and investigated. The combination of SDT with nanoparticles-based sonosensitizers and autophagy inhibition proves to be a superior therapy with high specificity and accuracy and improves the outcomes of traditional tumor treatment methods. As an innovative tumor treatment concept, few researchers have carried out investigations in this field. However, as Qu et al. (2020) and Feng et al. (2019) suggested, this combinational tumor therapy method is sensitive, effective, and safe.

Qu et al. (2020) designed a novel “all-in-one” nanosensitizer and improved the SDT efficiency in glioma therapy. The “all-in-one” nanosensitizer incorporates the sonoactive chlorin e6 (Ce6) and hydroxychloroquine (HCQ) into angiopep-2 peptide-modified liposomes (APL), in which APL acts as the NP platform for drug delivery, Ce6 acts as the sonosensitizer, and HCQ acts as the autophagy inhibitor. APL can selectively accumulate in the glioma cells in the brain, which is a good strategy for precise drug delivery and can help minimize the side effects of the applied drugs on orthotopic cells. As the autophagy helps tumor cells adapt to oxidative injury and other stress after SDT by recycling the damaged mitochondria, the autophagy inhibitor HCQ prevents the above process and significantly enhances the SDT therapeutic effect. The mechanism of autophagy inhibitor improving SDT efficiency was proposed in this review as the autophagy blockage can enhance oxidative damage and increase the apoptosis response (Figure 4).

FIGURE 4

A similar therapeutic method was reported by Feng et al. (2019), in which the sonosensitizer hollow mesoporous titanium dioxide NPs (HMTNPs), along with the autophagy inhibitor HCQ, were combined and coated with cancer cell membranes (CCM). The biomimetic CCM coating allowed the CCM-HMTNPs/HCQ drugs to be delivered to target tumor cells. Under US irradiation during SDT, HCQ was released to block the autophagy process. Moreover, the vessel normalization effect of HCQ improved the tumor cell hypoxia situation, which significantly promoted the oxygen-dependent HMTNPs-mediated SDT (Figure 5). It was concluded that the CCM-HMTNPs/HCQ drugs highly enhanced the sensitivity and efficiency of SDT on breast tumor cells (Feng et al., 2019).

FIGURE 5

Zhou et al. (2021) constructed an “all-in-one” nanoliposomes co-encapsulating sonosensitizers protoporphyrin IX (PpIX) and autophagy inhibitor 3-MA. It has been demonstrated that SDT induced cytoprotective pro-survival autophagy with alleviating apoptosis through the MAPK signaling pathway. Combining SDT and autophagy blockage significantly decreased the cell resistance to intracellular oxidative stress and resulted in a remarkable synergistic effect on cancer therapy (Figure 6).

FIGURE 6

Therefore, applying autophagy inhibitors to improve the sensitivity of SDT in tumor therapy is expected to provide a new and promising strategy to increase the SDT efficiency and sensitivity.

5 Summary and outlook

Originated and developed from PDT, SDT is a novel non-invasive tumor therapy. The advantages of SDT include deep tissue penetration, high precision, low side effects, and good patient compliance. SDT refers to the “cavity effect” generated by the irradiation of ultrasound at a specific frequency on tumors in deep tissues. Under US irradiation, the sonosensitive accumulated by tumor cells changes them from the ground state to the excited state and reacts with surrounding oxygen molecules to produce a large number of ROS, resulting in tumor cell death. SDT has made great progress in the treatment of tumors, and there have been many studies on the treatment of pancreatic cancer, liver cancer, breast cancer and other deep tumors. How to improve the efficiency of SDT is still the focus and difficulty of sonodynamic research.

Firstly, the efficiency of SDT highly relies on the sonosensitizer, and the major challenge for the application of SDT lies in the poor sonosensitizer delivery accuracy. With the development of nanotechnology, NPs are introduced to deliver the sonosensitizers to target tissues or tumor cells with high specificity. Many researchers have investigated the suitable NPs to be used as target delivery carriers, which are reviewed in this paper. Secondly, the main mechanism of SDT is that US uses oxygen in tumor cells to produce a large number of ROS to destroy tumor cells. Increasing the production of ROS can fundamentally improve the efficacy of SDT. Studies have shown that reactive oxygen species can activate autophagy through a variety of pathways, degrade damaged proteins and organelles in cells, and mediate cell survival or death. Wang et al. (Wang et al., 2013a; Wang et al., 2013b) found that SDT activated autophagy while inducing apoptosis, and the activated autophagy inhibited apoptosis and protected tumor cells in 2013. Many successive studies have found that SDT-activated autophagy depends on ROS production, and activated autophagy helps tumor cells survive, which was summarized in this paper. It is speculated that avoiding the activation of protective autophagy during SDT can effectively improve the treatment sensitivity. State of the art therapeutic technique is the combination of SDT with nanoparticles-based sonosensitizers together with autophagy inhibition, which proves to be a superior therapy with high specificity and accuracy and improves the outcomes of traditional tumor treatment methods. Few investigations have been done in this area and are summarized in this review. Qu et al. (2020) used Angiopep-2 peptide modified liposomes to deliver Ce6, an acoustic sensitizer, and HCQ, an autophagy inhibitor, simultaneously to improve the acoustic dynamic therapy effect of glioma. Feng et al. (2019) used hollow mesoporous titanium dioxide nanoparticles to deliver the autophagy inhibitor HCQ and improve the SDT effect of breast cancer. Zhou et al. (2021) used liposomes to deliver acoustic sensitizer PpIX/autophagy inhibitor 3-MA synchronously, improving the therapeutic effect of acoustic dynamics on breast cancer.

Increasing the accumulation of sonosensitive agents in tumor sites using nanocarriers can increase the production of ROS, and then fundamentally improve the efficiency of sonodynamic therapy. The increase of ROS activated protective autophagy to inhibit the SDT efficacy. Therefore, it is speculated that the combination of targeted delivery of sonosensitizer and inhibition of autophagy can not only effectively kill tumor cells by increasing the production of ROS, but also avoid the activation of protective-autophagy by ROS. The findings in this review suggest that this is a promising tumor therapy, and more investigations need to be carried out in this area.

References

• 1

  AkselM.KesmezO.YavasA.BilginM. D. (2021). Titaniumdioxide mediated sonophotodynamic therapy against prostate cancer. J. Photochem. Photobiol. B225, 112333. 10.1016/j.jphotobiol.2021.112333

  • CrossRef
  • Google Scholar

• 2

  AmaravadiR.KimmelmanA. C.WhiteE. (2016). Recent insights into the function of autophagy in cancer. Genes Dev.30 (17), 1913–1930. 10.1101/gad.287524.116

  • CrossRef
  • Google Scholar

• 3

  AmaravadiR. K.KimmelmanA. C.DebnathJ. (2019). Targeting autophagy in cancer: Recent advances and future directions. Cancer Discov.9 (9), 1167–1181. 10.1158/2159-8290.cd-19-0292

  • CrossRef
  • Google Scholar

• 4

  AnJ.HuY. G.ChengK.LiC.HouX. L.WangG. L.et al (2020a). ROS-augmented and tumor-microenvironment responsive biodegradable nanoplatform for enhancing chemo-sonodynamic therapy. Biomaterials234, 119761. 10.1016/j.biomaterials.2020.119761

  • CrossRef
  • Google Scholar

• 5

  AnJ.HuY. G.LiC.HouX. L.ChengK.ZhangB.et al (2020b). A pH/Ultrasound dual-response biomimetic nanoplatform for nitric oxide gas-sonodynamic combined therapy and repeated ultrasound for relieving hypoxia. Biomaterials230. 10.1016/j.biomaterials.2019.119636

  • CrossRef
  • Google Scholar

• 6

  AntonioliM.Di RienzoM.PiacentiniM.FimiaG. M. (2017). Emerging mechanisms in initiating and terminating autophagy. Trends biochem. Sci.42 (1), 28–41. 10.1016/j.tibs.2016.09.008

  • CrossRef
  • Google Scholar

• 7

  AtmacaG. Y.AkselM.KeskinB.BilginM. D.ErdoğmuşA. (2021). The photo-physicochemical properties and in vitro sonophotodynamic therapy activity of Di-axially substituted silicon phthalocyanines on PC3 prostate cancer cell line. Dyes Pigments184, 108760. 10.1016/j.dyepig.2020.108760

  • CrossRef
  • Google Scholar

• 8

  BandyopachyayU.CuervoA. M. (2008). Entering the lysosome through a transient gate by chaperone-mediated autophagy. Autophagy4 (8), 1101–1103. 10.4161/auto.7150

  • CrossRef
  • Google Scholar

• 9

  BuytaertE.CallewaertG.HendrickxN.ScorranoL.HartmannD.MissiaenL.et al (2006). Role of endoplasmic reticulum depletion and multidomain proapoptotic BAX and BAK proteins in shaping cell death after hypericin-mediated photodynamic therapy. FASEB J.20 (6), 756–758. 10.1096/fj.05-4305fje

  • CrossRef
  • Google Scholar

• 10

  BuytaertE.MatrouleJ. Y.DurinckS.CloseP.KocanovaS.VandenheedeJ. R.et al (2008). Molecular effectors and modulators of hypericin-mediated cell death in bladder cancer cells. Oncogene27 (13), 1916–1929. 10.1038/sj.onc.1210825

  • CrossRef
  • Google Scholar

• 11

  CanaparoR.VarchiG.BallestriM.FogliettaF.SotgiuG.GuerriniA.et al (2013). Polymeric nanoparticles enhance the sonodynamic activity of meso-tetrakis (4-sulfonatophenyl) porphyrin in an in vitro neuroblastoma model. Int. J. Nanomedicine8, 4247–4263. 10.2147/ijn.s51070

  • CrossRef
  • Google Scholar

• 12

  CaoJ.PanQ.BeiS.ZhengM.SunZ.QiX.et al (2021). Concise nanoplatform of phycocyanin nanoparticle loaded with docetaxel for synergetic chemo-sonodynamic antitumor therapy. ACS Appl. Bio Mat.4 (9), 7176–7185. 10.1021/acsabm.1c00745

  • CrossRef
  • Google Scholar

• 13

  CaoW. J.MatkarP. N.ChenH. H.MofidA.Leong-PoiH. (2016). Microbubbles and ultrasound: Therapeutic applications in diabetic nephropathy. Adv. Exp. Med. Biol.880, 309–330. 10.1007/978-3-319-22536-4_17

  • CrossRef
  • Google Scholar

• 14

  CavalliR.MaranoF.ArgenzianoM.VareseA.FrairiaR.CatalanoM. G.et al (2018). Combining drug-loaded nanobubbles and extracorporeal shock waves for difficult-to-treat cancers. Curr. Drug Deliv.15 (6), 752–754. 10.2174/1567201814666171018120430

  • CrossRef
  • Google Scholar

• 15

  ChanE. Y. (2009). mTORC1 phosphorylates the ULK1-mAtg13-FIP200 autophagy regulatory complex. Sci. Signal.2 (84), pe51. 10.1126/scisignal.284pe51

  • CrossRef
  • Google Scholar

• 16

  ChangH.ZouZ. (2020). Targeting autophagy to overcome drug resistance: Further developments. J. Hematol. Oncol.13 (1), 159. 10.1186/s13045-020-01000-2

  • CrossRef
  • Google Scholar

• 17

  ChangZ.ShiG.JinJ.GuoH.GuoX.LuoF.et al (2013). Dual PI3K/mTOR inhibitor NVP-BEZ235-induced apoptosis of hepatocellular carcinoma cell lines is enhanced by inhibitors of autophagy. Int. J. Mol. Med.31 (6), 1449–1456. 10.3892/ijmm.2013.1351

  • CrossRef
  • Google Scholar

• 18

  ChenH.ZhouX.GaoY.ZhengB.TangF.HuangJ.et al (2014). Recent progress in development of new sonosensitizers for sonodynamic cancer therapy. Drug Discov. Today19 (4), 502–509. 10.1016/j.drudis.2014.01.010

  • CrossRef
  • Google Scholar

• 19

  ChenL.CongD.LiY.WangD.LiQ.HuS.et al (2017a). Combination of sonodynamic with temozolomide inhibits C6 glioma migration and promotes mitochondrial pathway apoptosis via suppressing NHE-1 expression. Ultrason. Sonochem.39, 654–661. 10.1016/j.ultsonch.2017.05.013

  • CrossRef
  • Google Scholar

• 20

  ChenL. C.ZhouS. F.SuL. C.SongJ. B. (2019). Gas-mediated cancer bioimaging and therapy. Acs Nano13 (10), 10887–10917. 10.1021/acsnano.9b04954

  • CrossRef
  • Google Scholar

• 21

  ChenM. J.XuA. R.HeW. Y.MaW. C.ShenS. (2017b). Ultrasound triggered drug delivery for mitochondria targeted sonodynamic therapy. J. Drug Deliv. Sci. Technol.39, 501–507. 10.1016/j.jddst.2017.05.009

  • CrossRef
  • Google Scholar

• 22

  ChengD.WangX.ZhouX.LiJ. (2021). Nanosonosensitizers with ultrasound-induced reactive oxygen species generation for cancer sonodynamic immunotherapy. Front. Bioeng. Biotechnol.9, 761218. 10.3389/fbioe.2021.761218

  • CrossRef
  • Google Scholar

• 23

  ChengL.QiuS.WangJ.ChenW.WangJ.DuW.et al (2022). A multifunctional nanocomposite based on Pt-modified black phosphorus nanosheets loading with l-arginine for synergistic gas-sonodynamic cancer therapy. Colloids Surfaces A Physicochem. Eng. Aspects638, 128284. 10.1016/j.colsurfa.2022.128284

  • CrossRef
  • Google Scholar

• 24

  ChoiH. S.JeongE.-H.LeeT.-G.KimS. Y.KimH.-R.KimC. H.et al (2013). Autophagy inhibition with monensin enhances cell cycle arrest and apoptosis induced by mTOR or epidermal growth factor receptor inhibitors in lung cancer cells. Tuberc. Respir. Dis.75 (1), 9–17. 10.4046/trd.2013.75.1.9

  • CrossRef
  • Google Scholar

• 25

  ChristianF.AnthonyD. F.VadrevuS.RiddellT.DayJ. P.McLeodR.et al (2010). p62 (SQSTM1) and cyclic AMP phosphodiesterase-4A4 (PDE4A4) locate to a novel, reversible protein aggregate with links to autophagy and proteasome degradation pathways. Cell. Signal.22 (10), 1576–1596. 10.1016/j.cellsig.2010.06.003

  • CrossRef
  • Google Scholar

• 26

  CookK. L.WärriA.Soto-PantojaD. R.ClarkeP. A.CruzM. I.ZwartA.et al (2014). Hydroxychloroquine inhibits autophagy to potentiate antiestrogen responsiveness in ER+ breast cancer. Clin. Cancer Res.20 (12), 3222–3232. 10.1158/1078-0432.ccr-13-3227

  • CrossRef
  • Google Scholar

• 27

  DannoD.KannoM.FujimotoS.FerilL. B.KondoT.NakamuraS.et al (2008). Effects of ultrasound on apoptosis induced by anti-CD20 antibody in CD20-positive B lymphoma cells. Ultrason. Sonochem.15 (4), 463–471. 10.1016/j.ultsonch.2007.08.004

  • CrossRef
  • Google Scholar

• 28

  DidenkoY. T.McNamaraW. B.IiiSuslickK. S. (2000). Molecular emission from single-bubble sonoluminescence. Nature407 (6806), 877–879. 10.1038/35038020

  • CrossRef
  • Google Scholar

• 29

  DingY.SongZ.LiuQ.WeiS.ZhouL.ZhouJ.et al (2017). An enhanced chemotherapeutic effect facilitated by sonication of MSN. Dalton Trans.46 (35), 11875–11883. 10.1039/c7dt02600e

  • CrossRef
  • Google Scholar

• 30

  EscoffreJ. M.DeckersR.BosC.MoonenC. (2016). Bubble-assisted ultrasound: Application in immunotherapy and vaccination. Adv. Exp. Med. Biol.880, 243–261. 10.1007/978-3-319-22536-4_14

  • CrossRef
  • Google Scholar

• 31

  FengQ.YangX.HaoY.WangN.FengX.HouL.et al (2019). Cancer cell membrane-biomimetic nanoplatform for enhanced sonodynamic therapy on breast cancer via autophagy regulation strategy. ACS Appl. Mat. Interfaces11 (36), 32729–32738. 10.1021/acsami.9b10948

  • CrossRef
  • Google Scholar

• 32

  FengQ.ZhangW.YangX.LiY.HaoY.ZhangH.et al (2018). pH/ultrasound dual-responsive gas generator for ultrasound imaging-guided therapeutic inertial cavitation and sonodynamic therapy. Adv. Healthc. Mat.7 (5), 1700957. 10.1002/adhm.201700957

  • CrossRef
  • Google Scholar

• 33

  ForbesM. M.SteinbergR. L.O'BrienW. D. (2011). Frequency-dependent evaluation of the role of definity in producing sonoporation of Chinese hamster ovary cells. J. Ultrasound Med.30 (1), 61–69. 10.7863/jum.2011.30.1.61

  • CrossRef
  • Google Scholar

• 34

  FujitaN.ItohT.OmoriH.FukudaM.NodaT.YoshimoriT.et al (2008). The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy. Mol. Biol. Cell19 (5), 2092–2100. 10.1091/mbc.e07-12-1257

  • CrossRef
  • Google Scholar

• 35

  GaoH. J.ZhangW. M.WangX. H.ZhengR. N. (2010). Adriamycin enhances the sonodynamic effect of chlorin e6 against the proliferation of human breast cancer MDA-MB-231 cells in vitro. Nan Fang. Yi Ke Da Xue Xue Bao30 (10), 2291–2294.

  • Google Scholar

• 36

  GengB.XuS.ShenL.FangF.ShiW.PanD.et al (2021). Multifunctional carbon dot/MXene heterojunctions for alleviation of tumor hypoxia and enhanced sonodynamic therapy. Carbon179, 493–504. 10.1016/j.carbon.2021.04.070

  • CrossRef
  • Google Scholar

• 37

  GengJ.KlionskyD. J. (2008). The Atg8 and Atg12 ubiquitin-like conjugation systems in macroautophagy. 'Protein modifications: Beyond the usual suspects' review series. EMBO Rep.9 (9), 859–864. 10.1038/embor.2008.163

  • CrossRef
  • Google Scholar

• 38

  GlickD.BarthS.MacleodK. F. (2010). Autophagy: Cellular and molecular mechanisms. J. Pathol.221 (1), 3–12. 10.1002/path.2697

  • CrossRef
  • Google Scholar

• 39

  GoldbergS. B.SupkoJ. G.NealJ. W.MuzikanskyA.DigumarthyS.FidiasP.et al (2012). A phase I study of erlotinib and hydroxychloroquine in advanced non-small-cell lung cancer. J. Thorac. Oncol.7 (10), 1602–1608. 10.1097/JTO.0b013e318262de4a

  • CrossRef
  • Google Scholar

• 40

  GuanS.LiuX.LiC.WangX.CaoD.WangJ.et al (2022). Intracellular mutual amplification of oxidative stress and inhibition multidrug resistance for enhanced sonodynamic/chemodynamic/chemo therapy. Small18, e2107160. 10.1002/smll.202107160

  • CrossRef
  • Google Scholar

• 41

  HachimineK.ShibaguchiH.KurokiM.YamadaH.KinugasaT.NakaeY.et al (2007). Sonodynamic therapy of cancer using a novel porphyrin derivative, DCPH-P-Na(I), which is devoid of photosensitivity. Cancer Sci.98 (6), 916–920. 10.1111/j.1349-7006.2007.00468.x

  • CrossRef
  • Google Scholar

• 42

  HanadaT.NodaN. N.SatomiY.IchimuraY.FujiokaY.TakaoT.et al (2007). The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy. J. Biol. Chem.282 (52), 37298–37302. 10.1074/jbc.C700195200

  • CrossRef
  • Google Scholar

• 43

  HaraT.TakamuraA.KishiC.IemuraS.NatsumeT.GuanJ. L.et al (2008). FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells. J. Cell Biol.181 (3), 497–510. 10.1083/jcb.200712064

  • CrossRef
  • Google Scholar

• 44

  HaradaY.OgawaK.IrieY.EndoH.FerilL. B.Jr.UemuraT.et al (2011). Ultrasound activation of TiO2 in melanoma tumors. J. Control. Release149 (2), 190–195. 10.1016/j.jconrel.2010.10.012

  • CrossRef
  • Google Scholar

• 45

  HelgasonG. V.HolyoakeT. L.RyanK. M. (2013). Role of autophagy in cancer prevention, development and therapy. Essays Biochem.55, 133–151. 10.1042/bse0550133

  • CrossRef
  • Google Scholar

• 46

  HiraokaW.HondaH.FerilL. B.KudoN.KondoT. (2006). Comparison between sonodynamic effect and photodynamic effect with photosensitizers on free radical formation and cell killing. Ultrason. Sonochem.13 (6), 535–542. 10.1016/j.ultsonch.2005.10.001

  • CrossRef
  • Google Scholar

• 47

  HosokawaN.HaraT.KaizukaT.KishiC.TakamuraA.MiuraY.et al (2009a). Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol. Biol. Cell20 (7), 1981–1991. 10.1091/mbc.e08-12-1248

  • CrossRef
  • Google Scholar

• 48

  HosokawaN.SasakiT.IemuraS.NatsumeT.HaraT.MizushimaN.et al (2009b). Atg101, a novel mammalian autophagy protein interacting with Atg13. Autophagy5 (7), 973–979. 10.4161/auto.5.7.9296

  • CrossRef
  • Google Scholar

• 49

  HouR.LiangX.LiX.ZhangX.MaX.WangF.et al (2020). In situ conversion of rose bengal microbubbles into nanoparticles for ultrasound imaging guided sonodynamic therapy with enhanced antitumor efficacy. Biomater. Sci.8 (9), 2526–2536. 10.1039/c9bm02046b

  • CrossRef
  • Google Scholar

• 50

  HsinI. L.OuC. C.WuT. C.JanM. S.WuM. F.ChiuL. Y.et al (2011). GMI, an immunomodulatory protein from Ganoderma microsporum, induces autophagy in non-small cell lung cancer cells. Autophagy7 (8), 873–882. 10.4161/auto.7.8.15698

  • CrossRef
  • Google Scholar

• 51

  HuangJ.LiuF.HanX.ZhangL.HuZ.JiangQ.et al (2018). Nanosonosensitizers for highly efficient sonodynamic cancer theranostics. Theranostics8 (22), 6178–6194. 10.7150/thno.29569

  • CrossRef
  • Google Scholar

• 52

  HuangJ.XiaoZ.AnY.HanS.WuW.WangY.et al (2021). Nanodrug with dual-sensitivity to tumor microenvironment for immuno-sonodynamic anti-cancer therapy. Biomaterials269, 120636. 10.1016/j.biomaterials.2020.120636

  • CrossRef
  • Google Scholar

• 53

  HuangZ. (2005). A review of progress in clinical photodynamic therapy. Technol. Cancer Res. Treat.4 (3), 283–293. 10.1177/153303460500400308

  • CrossRef
  • Google Scholar

• 54

  ImaiK.HaoF.FujitaN.TsujiY.OeY.ArakiY.et al (2016). Atg9A trafficking through the recycling endosomes is required for autophagosome formation. J. Cell Sci.129 (20), 3781–3791. 10.1242/jcs.196196

  • CrossRef
  • Google Scholar

• 55

  IshibashiK.FujitaN.KannoE.OmoriH.YoshimoriT.ItohT.et al (2011). Atg16L2, a novel isoform of mammalian Atg16L that is not essential for canonical autophagy despite forming an Atg12–5-16L2 complex. Autophagy7 (12), 1500–1513. 10.4161/auto.7.12.18025

  • CrossRef
  • Google Scholar

• 56

  ItakuraE.Kishi-ItakuraC.MizushimaN. (2012). The hairpin-type tail-anchored SNARE syntaxin 17 targets to autophagosomes for fusion with endosomes/lysosomes. Cell151 (6), 1256–1269. 10.1016/j.cell.2012.11.001

  • CrossRef
  • Google Scholar

• 57

  JeonJ.YoonB.SongS. H.UmW.SongY.LeeJ.et al (2022). Chemiluminescence resonance energy transfer-based immunostimulatory nanoparticles for sonoimmunotherapy. Biomaterials283, 121466. 10.1016/j.biomaterials.2022.121466

  • CrossRef
  • Google Scholar

• 58

  JiangP.NishimuraT.SakamakiY.ItakuraE.HattaT.NatsumeT.et al (2014). The HOPS complex mediates autophagosome-lysosome fusion through interaction with syntaxin 17. Mol. Biol. Cell25 (8), 1327–1337. 10.1091/mbc.E13-08-0447

  • CrossRef
  • Google Scholar

• 59

  JiangQ.QiaoB.LinX.CaoJ.ZhangN.GuoH.et al (2022). A hydrogen peroxide economizer for on-demand oxygen production-assisted robust sonodynamic immunotherapy. Theranostics12 (1), 59–75. 10.7150/thno.64862

  • CrossRef
  • Google Scholar

• 60

  JiangY.KouJ.HanX.LiX.ZhongZ.LiuZ.et al (2017). ROS-dependent activation of autophagy through the PI3K/Akt/mTOR pathway is induced by hydroxysafflor yellow A-sonodynamic therapy in THP-1 macrophages. Oxid. Med. Cell. Longev.2017, 8519169. 10.1155/2017/8519169

  • CrossRef
  • Google Scholar

• 61

  KabeyaY.MizushimaN.UenoT.YamamotoA.KirisakoT.NodaT.et al (2000). LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. Embo J.19 (21), 5720–5728. 10.1093/emboj/19.21.5720

  • CrossRef
  • Google Scholar

• 62

  Kaleta-RichterM.Kawczyk-KrupkaA.AebisherD.Bartusik-AebisherD.CzubaZ.CieślarG.et al (2019). The capability and potential of new forms of personalized colon cancer treatment: Immunotherapy and Photodynamic Therapy. Photodiagnosis Photodyn. Ther.25, 253–258. 10.1016/j.pdpdt.2019.01.004

  • CrossRef
  • Google Scholar

• 63

  KayaniZ.Dehdari VaisR.SoratijahromiE.MohammadiS.SattarahmadyN. (2021). Curcumin-gold-polyethylene glycol nanoparticles as a nanosensitizer for photothermal and sonodynamic therapies: In vitro and animal model studies. Photodiagnosis Photodyn. Ther.33, 102139. 10.1016/j.pdpdt.2020.102139

  • CrossRef
  • Google Scholar

• 64

  KesselD.OleinickN. L. (2009). Initiation of autophagy by photodynamic therapy. Methods Enzymol.453, 1–16. 10.1016/s0076-6879(08)04001-9

  • CrossRef
  • Google Scholar

• 65

  KesselD.VicenteM. G.ReinersJ. J.Jr. (2006). Initiation of apoptosis and autophagy by photodynamic therapy. Autophagy2 (4), 289–290. 10.4161/auto.2792

  • CrossRef
  • Google Scholar

• 66

  KitanakaC.KuchinoY. (1999). Caspase-independent programmed cell death with necrotic morphology. Cell Death Differ.6 (6), 508–515. 10.1038/sj.cdd.4400526

  • CrossRef
  • Google Scholar

• 67

  KocaturkN. M.AkkocY.KigC.BayraktarO.GozuacikD.KutluO.et al (2019). Autophagy as a molecular target for cancer treatment. Eur. J. Pharm. Sci.134, 116–137. 10.1016/j.ejps.2019.04.011

  • CrossRef
  • Google Scholar

• 68

  KondoT.KanoE. (1987). Enhancement of hyperthermic cell killing by non-thermal effect of ultrasound. Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med.51 (1), 157–166. 10.1080/09553008714550591

  • CrossRef
  • Google Scholar

• 69

  KouJ. Y.LiY.ZhongZ. Y.JiangY. Q.LiX. S.HanX. B.et al (2017). Berberine-sonodynamic therapy induces autophagy and lipid unloading in macrophage. Cell Death Dis.8 (1), e2558. 10.1038/cddis.2016.354

  • CrossRef
  • Google Scholar

• 70

  KwonS.KoH.YouD. G.KataokaK.ParkJ. H. (2019). Nanomedicines for reactive oxygen species mediated approach: An emerging paradigm for cancer treatment. Acc. Chem. Res.52 (7), 1771–1782. 10.1021/acs.accounts.9b00136

  • CrossRef
  • Google Scholar

• 71

  LeeH. O.MustafaA.HudesG. R.KrugerW. D. (2015). Hydroxychloroquine destabilizes phospho-S6 in human renal carcinoma cells. PLoS One10 (7), e0131464. 10.1371/journal.pone.0131464

  • CrossRef
  • Google Scholar

• 72

  LevyJ. M. M.TowersC. G.ThorburnA. (2017). Targeting autophagy in cancer. Nat. Rev. Cancer17 (9), 528–542. 10.1038/nrc.2017.53

  • CrossRef
  • Google Scholar

• 73

  LiG.ZhongX.WangX.GongF.LeiH.ZhouY.et al (2022). Titanium carbide nanosheets with defect structure for photothermal-enhanced sonodynamic therapy. Bioact. Mat.8, 409–419. 10.1016/j.bioactmat.2021.06.021

  • CrossRef
  • Google Scholar

• 74

  LiJ.LuoY.PuK. (2021). Electromagnetic nanomedicines for combinational cancer immunotherapy. Angew. Chem. Int. Ed. Engl.60 (23), 12682–12705. 10.1002/anie.202008386

  • CrossRef
  • Google Scholar

• 75

  LiQ.LiuQ.WangP.FengX.WangH.WangX.et al (2014a). The effects of Ce6-mediated sono-photodynamic therapy on cell migration, apoptosis and autophagy in mouse mammary 4T1 cell line. Ultrasonics54 (4), 981–989. 10.1016/j.ultras.2013.11.009

  • CrossRef
  • Google Scholar

• 76

  LiQ.WangX.WangP.ZhangK.WangH.FengX.et al (2014b). Efficacy of chlorin e6-mediated sono-photodynamic therapy on 4T1 cells. Cancer biother. Radiopharm.29 (1), 42–52. 10.1089/cbr.2013.1526

  • CrossRef
  • Google Scholar

• 77

  LiX. J.FengJ.ZhangR.WangJ. D.SuT.TianZ. H.et al (2016c). Quaternized chitosan/alginate-Fe3O4 magnetic nanoparticles enhance the chemosensitization of multidrug-resistant gastric carcinoma by regulating cell autophagy activity in mice. J. Biomed. Nanotechnol.12 (5), 948–961. 10.1166/jbn.2016.2232

  • CrossRef
  • Google Scholar

• 78

  LiX.ZhangX.ZhengL.KouJ.ZhongZ.JiangY.et al (2016a). Hypericin-mediated sonodynamic therapy induces autophagy and decreases lipids in THP-1 macrophage by promoting ROS-dependent nuclear translocation of TFEB. Cell Death Dis.7 (12), e2527. 10.1038/cddis.2016.433

  • CrossRef
  • Google Scholar

• 79

  LiX.ZhangX.ZhengL.KouJ.ZhongZ.JiangY.et al (2016b). Hypericin-mediated sonodynamic therapy induces autophagy and decreases lipids in THP-1 macrophage by promoting ROS-dependent nuclear translocation of TFEB. Cell Death Dis.7 (12), e2527. 10.1038/cddis.2016.433

  • CrossRef
  • Google Scholar

• 80

  LiY.HaoL.LiuF.YinL.YanS.ZhaoH.et al (2019). Cell penetrating peptide-modified nanoparticles for tumor targeted imaging and synergistic effect of sonodynamic/HIFU therapy. Int. J. Nanomedicine14, 5875–5894. 10.2147/ijn.s212184

  • CrossRef
  • Google Scholar

• 81

  LiY.XieJ.UmW.YouD. G.KwonS.ZhangL.et al (2020). Sono/photodynamic nanomedicine‐elicited cancer immunotherapy. Adv. Funct. Mat.31 (12), 2008061. 10.1002/adfm.202008061

  • CrossRef
  • Google Scholar

• 82

  LiZ.HanJ.YuL.QianX.XingH.LinH.et al (2018). Synergistic sonodynamic/chemotherapeutic suppression of hepatocellular carcinoma by targeted biodegradable mesoporous nanosonosensitizers. Adv. Funct. Mat.28 (26), 1800145. 10.1002/adfm.201800145

  • CrossRef
  • Google Scholar

• 83

  LiangJ. L.LuoG. F.ChenW. H.ZhangX. Z. (2021). Recent advances in engineered materials for immunotherapy-involved combination cancer therapy. Adv. Mat.33 (31), e2007630. 10.1002/adma.202007630

  • CrossRef
  • Google Scholar

• 84

  LiangS.DengX.MaP.ChengZ.LinJ. (2020a). Recent advances in nanomaterial-assisted combinational sonodynamic cancer therapy. Adv. Mat.32, e2003214. 10.1002/adma.202003214

  • CrossRef
  • Google Scholar

• 85

  LiangS.DengX. R.XuG. Y.XiaoX.WangM. F.GuoX. S.et al (2020b). A novel Pt-TiO2 heterostructure with oxygen-deficient layer as bilaterally enhanced sonosensitizer for synergistic chemo-sonodynamic cancer therapy. Adv. Funct. Mat.30 (13), 1908598. 10.1002/adfm.201908598

  • CrossRef
  • Google Scholar

• 86

  LinX.HeT.TangR.LiQ.WuN.ZhouY.et al (2022). Biomimetic nanoprobe-augmented triple therapy with photothermal, sonodynamic and checkpoint blockade inhibits tumor growth and metastasis. J. Nanobiotechnology20 (1), 80. 10.1186/s12951-022-01287-y

  • CrossRef
  • Google Scholar

• 87

  LinX. H.QiuY.SongL.ChenS.ChenX. F.HuangG. M.et al (2019). Ultrasound activation of liposomes for enhanced ultrasound imaging and synergistic gas and sonodynamic cancer therapy. Nanoscale Horiz.4 (3), 747–756. 10.1039/c8nh00340h

  • CrossRef
  • Google Scholar

• 88

  LinX.HuangR.HuangY.WangK.LiH.BaoY.et al (2021). Nanosonosensitizer-Augmented sonodynamic therapy combined with checkpoint blockade for cancer immunotherapy. Int. J. Nanomedicine16, 1889–1899. 10.2147/IJN.S290796

  • CrossRef
  • Google Scholar

• 89

  LiuM.KhanA. R.JiJ.LinG.ZhaoX.ZhaiG.et al (2018). Crosslinked self-assembled nanoparticles for chemo-sonodynamic combination therapy favoring antitumor, antimetastasis management and immune responses. J. Control. Release290, 150–164. 10.1016/j.jconrel.2018.10.007

  • CrossRef
  • Google Scholar

• 90

  LiuQ.SunS.XiaoY.QiH.ShangZ.ZhangJ.et al (2003). Study of cell killing and morphology on S180 by ultrasound activating hematoporphyrin derivatives. Sci. China. C Life Sci.46 (3), 253–262. 10.1360/03yc9027

  • CrossRef
  • Google Scholar

• 91

  LiuX.LiW.GengS.MengQ. G.BiZ. G. (2015). Apoptosis induced by sonodynamic therapy in human osteosarcoma cells in vitro. Mol. Med. Rep.12 (1), 1183–1188. 10.3892/mmr.2015.3479

  • CrossRef
  • Google Scholar

• 92

  LiuY.WanG.GuoH.LiuY.ZhouP.WangH.et al (2017). A multifunctional nanoparticle system combines sonodynamic therapy and chemotherapy to treat hepatocellular carcinoma. Nano Res.10 (3), 834–855. 10.1007/s12274-016-1339-8

  • CrossRef
  • Google Scholar

• 93

  LiuY.WangP.LiuQ.WangX. (2016). Sinoporphyrin sodium triggered sono-photodynamic effects on breast cancer both in vitro and in vivo. Ultrason. Sonochem.31, 437–448. 10.1016/j.ultsonch.2016.01.038

  • CrossRef
  • Google Scholar

• 94

  LiuZ.LiJ.ChenW.LiuL.YuF. (2020). Light and sound to trigger the pandora's box against breast cancer: A combination strategy of sonodynamic, photodynamic and photothermal therapies. Biomaterials232, 119685. 10.1016/j.biomaterials.2019.119685

  • CrossRef
  • Google Scholar

• 95

  LiuZ.WangD.LiJ.JiangY. (2019). Self-assembled peptido-nanomicelles as an engineered formulation for synergy-enhanced combinational SDT, PDT and chemotherapy to nasopharyngeal carcinoma. Chem. Commun.55 (69), 10226–10229. 10.1039/c9cc05463d

  • CrossRef
  • Google Scholar

• 96

  LoganK.FogliettaF.NesbittH.ShengY.McKaigT.KamilaS.et al (2019). Targeted chemo-sonodynamic therapy treatment of breast tumours using ultrasound responsive microbubbles loaded with paclitaxel, doxorubicin and Rose Bengal. Eur. J. Pharm. Biopharm.139, 224–231. 10.1016/j.ejpb.2019.04.003

  • CrossRef
  • Google Scholar

• 97

  LuJ.HeL.BehrendsC.ArakiM.ArakiK.Jun WangQ.et al (2014). NRBF2 regulates autophagy and prevents liver injury by modulating Atg14L-linked phosphatidylinositol-3 kinase III activity. Nat. Commun.5, 3920. 10.1038/ncomms4920

  • CrossRef
  • Google Scholar

• 98

  LvY.ZhengJ.ZhouQ.JiaL.WangC.LiuN.et al (2017). Antiproliferative and apoptosis-inducing effect of exo-protoporphyrin IX based sonodynamic therapy on human oral squamous cell carcinoma. Sci. Rep.7, 40967. 10.1038/srep40967

  • CrossRef
  • Google Scholar

• 99

  MahalingamD.MitaM.SarantopoulosJ.WoodL.AmaravadiR. K.DavisL. E.et al (2014). Combined autophagy and HDAC inhibition: a phase I safety, tolerability, pharmacokinetic, and pharmacodynamic analysis of hydroxychloroquine in combination with the HDAC inhibitor vorinostat in patients with advanced solid tumors. Autophagy10 (8), 1403–1414. 10.4161/auto.29231

  • CrossRef
  • Google Scholar

• 100

  MatsunagaK.SaitohT.TabataK.OmoriH.SatohT.KurotoriN.et al (2009). Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. Nat. Cell Biol.11 (4), 385–396. 10.1038/ncb1846

  • CrossRef
  • Google Scholar

• 101

  McHaleA. P.CallanJ. F.NomikouN.FowleyC.CallanB. (2016). Sonodynamic therapy: Concept, mechanism and application to cancer treatment. Adv. Exp. Med. Biol.880, 429–450. 10.1007/978-3-319-22536-4_22

  • CrossRef
  • Google Scholar

• 102

  MisikV.RieszP. (2000). Free radical intermediates in sonodynamic therapy. Ann. N. Y. Acad. Sci.899, 335–348. 10.1111/j.1749-6632.2000.tb06198.x

  • CrossRef
  • Google Scholar

• 103

  MonyV. K.BenjaminS.O'RourkeE. J. (2016). A lysosome-centered view of nutrient homeostasis. Autophagy12 (4), 619–631. 10.1080/15548627.2016.1147671

  • CrossRef
  • Google Scholar

• 104

  NakatogawaH. (2013). Two ubiquitin-like conjugation systems that mediate membrane formation during autophagy. Essays Biochem.55, 39–50. 10.1042/bse0550039

  • CrossRef
  • Google Scholar

• 105

  NeneL. C.NyokongT. (2021). Photo-sonodynamic combination activity of cationic morpholino-phthalocyanines conjugated to nitrogen and nitrogen-sulfur doped graphene quantum dots against MCF-7 breast cancer cell line in vitro. Photodiagnosis Photodyn. Ther.36, 102573. 10.1016/j.pdpdt.2021.102573

  • CrossRef
  • Google Scholar

• 106

  NesbittH.ShengY.KamilaS.LoganK.ThomasK.CallanB.et al (2018). Gemcitabine loaded microbubbles for targeted chemo-sonodynamic therapy of pancreatic cancer. J. Control. Release279, 8–16. 10.1016/j.jconrel.2018.04.018

  • CrossRef
  • Google Scholar

• 107

  Nora FrulioH. T.DeckersR.DeckersR.LepreuxS.MoonenC.QuessonB. (2010). Influence of ultrasound induced cavitation on magnetic resonance imaging contrast in the rat liver in the presence of macromolecular contrast agent. Invest. Radiol.45 (5), 282–287. 10.1097/RLI.0b013e3181dac2a7

  • CrossRef
  • Google Scholar

• 108

  OhmuraT.FukushimaT.ShibaguchiH.YoshizawaS.InoueT.KurokiM.et al (2011). Sonodynamic therapy with 5-aminolevulinic acid and focused ultrasound for deep-seated intracranial glioma in rat. Anticancer Res.31 (7), 2527–2533.

  • Google Scholar

• 109

  OrsiA.RaziM.DooleyH. C.RobinsonD.WestonA. E.CollinsonL. M.et al (2012). Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy. Mol. Biol. Cell23 (10), 1860–1873. 10.1091/mbc.E11-09-0746

  • CrossRef
  • Google Scholar

• 110

  PadillaF.PutsR.VicoL.GuignandonA.RaumK. (2016). Stimulation of bone repair with ultrasound. Adv. Exp. Med. Biol.880, 385–427. 10.1007/978-3-319-22536-4_21

  • CrossRef
  • Google Scholar

• 111

  PanX.BaiL.WangH.WuQ.WangH.LiuS.et al (2018a). Metal-organic-framework-Derived carbon nanostructure augmented sonodynamic cancer therapy. Adv. Mat.30 (23), e1800180. 10.1002/adma.201800180

  • CrossRef
  • Google Scholar

• 112

  PanX.WangH.WangS.SunX.WangL.WangW.et al (2018b). Sonodynamic therapy (SDT): A novel strategy for cancer nanotheranostics. Sci. China. Life Sci.61 (4), 415–426. 10.1007/s11427-017-9262-x

  • CrossRef
  • Google Scholar

• 113

  PanX.WangW.HuangZ.LiuS.GuoJ.ZhangF.et al (2020). MOF-derived double-layer hollow nanoparticles with oxygen generation ability for multimodal imaging-guided sonodynamic therapy. Angew. Chem. Int. Ed. Engl.59 (32), 13557–13561. 10.1002/anie.202004894

  • CrossRef
  • Google Scholar

• 114

  ParkJ. M.JungC. H.SeoM.OttoN. M.GrunwaldD.KimK. H.et al (2016). The ULK1 complex mediates MTORC1 signaling to the autophagy initiation machinery via binding and phosphorylating ATG14. Autophagy12 (3), 547–564. 10.1080/15548627.2016.1140293

  • CrossRef
  • Google Scholar

• 115

  ParzychK. R.KlionskyD. J. (2014). An overview of autophagy: Morphology, mechanism, and regulation. Antioxid. Redox Signal.20 (3), 460–473. 10.1089/ars.2013.5371

  • CrossRef
  • Google Scholar

• 116

  PeltJ.BusattoS.FerrariM.ThompsonE. A.ModyK.WolframJ.et al (2018). Chloroquine and nanoparticle drug delivery: A promising combination. Pharmacol. Ther.191, 43–49. 10.1016/j.pharmthera.2018.06.007

  • CrossRef
  • Google Scholar

• 117

  QianX.ZhengY.ChenY. (2016). Micro/nanoparticle-Augmented sonodynamic therapy (SDT): Breaking the depth shallow of photoactivation. Adv. Mat.28 (37), 8097–8129. 10.1002/adma.201602012

  • CrossRef
  • Google Scholar

• 118

  QuF.WangP.ZhangK.ShiY.LiY.LiC.et al (2020). Manipulation of Mitophagy by "All-in-One" nanosensitizer augments sonodynamic glioma therapy. Autophagy16 (8), 1413–1435. 10.1080/15548627.2019.1687210

  • CrossRef
  • Google Scholar

• 119

  RangwalaR.ChangY. C.HuJ.AlgazyK. M.EvansT. L.FecherL. A.et al (2014). Combined MTOR and autophagy inhibition: phase I trial of hydroxychloroquine and temsirolimus in patients with advanced solid tumors and melanoma. Autophagy10 (8), 1391–1402. 10.4161/auto.29119

  • CrossRef
  • Google Scholar

• 120

  RavikumarB.MoreauK.JahreissL.PuriC.RubinszteinD. C. (2010). Plasma membrane contributes to the formation of pre-autophagosomal structures. Nat. Cell Biol.12 (8), 747–757. 10.1038/ncb2078

  • CrossRef
  • Google Scholar

• 121

  RenQ.YuN.WangL.WenM.GengP.JiangQ.et al (2022). Nanoarchitectonics with metal-organic frameworks and platinum nanozymes with improved oxygen evolution for enhanced sonodynamic/chemo-therapy. J. Colloid Interface Sci.614, 147–159. 10.1016/j.jcis.2022.01.050

  • CrossRef
  • Google Scholar

• 122

  RengengL.QianyuZ.YuehongL.ZhongzhongP.LiboL. (2017). Sonodynamic therapy, a treatment developing from photodynamic therapy. Photodiagnosis Photodyn. Ther.19, 159–166. 10.1016/j.pdpdt.2017.06.003

  • CrossRef
  • Google Scholar

• 123

  RkeinA. M.OzogD. M. (2014). Photodynamic therapy. Dermatol. Clin.32 (3), 415–425. 10.1016/j.det.2014.03.009

  • CrossRef
  • Google Scholar

• 124

  RosenfeldM. R.YeX.SupkoJ. G.DesideriS.GrossmanS. A.BremS.et al (2014). A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme. Autophagy10 (8), 1359–1368. 10.4161/auto.28984

  • CrossRef
  • Google Scholar

• 125

  SatooK.NodaN. N.KumetaH.FujiokaY.MizushimaN.OhsumiY.et al (2009). The structure of Atg4B-LC3 complex reveals the mechanism of LC3 processing and delipidation during autophagy. Embo J.28 (9), 1341–1350. 10.1038/emboj.2009.80

  • CrossRef
  • Google Scholar

• 126

  ShaneiA.SazgarniaA.Tayyebi MeibodiN.EshghiH.Hassanzadeh-KhayyatM.EsmailyH.et al (2012). Sonodynamic therapy using protoporphyrin IX conjugated to gold nanoparticles: An in vivo study on a colon tumor model. Iran. J. Basic Med. Sci.15 (2), 759–767.

  • Google Scholar

• 127

  ShenQ.ShiY.LiuJ.SuH.HuangJ.ZhangY.et al (2021). Acetylation of STX17 (syntaxin 17) controls autophagosome maturation. Autophagy17 (5), 1157–1169. 10.1080/15548627.2020.1752471

  • CrossRef
  • Google Scholar

• 128

  ShenS.WuL.LiuJ.XieM.ShenH.QiX.et al (2015). Core-shell structured Fe3O4@TiO2-doxorubicin nanoparticles for targeted chemo-sonodynamic therapy of cancer. Int. J. Pharm.486 (1-2), 380–388. 10.1016/j.ijpharm.2015.03.070

  • CrossRef
  • Google Scholar

• 129

  ShiJ.ChenZ.WangB.WangL.LuT.ZhangZ.et al (2015). Reactive oxygen species-manipulated drug release from a smart envelope-type mesoporous titanium nanovehicle for tumor sonodynamic-chemotherapy. ACS Appl. Mat. Interfaces7 (51), 28554–28565. 10.1021/acsami.5b09937

  • CrossRef
  • Google Scholar

• 130

  ShiT. T.YuX. X.YanL. J.XiaoH. T. (2017). Research progress of hydroxychloroquine and autophagy inhibitors on cancer. Cancer Chemother. Pharmacol.79 (2), 287–294. 10.1007/s00280-016-3197-1

  • CrossRef
  • Google Scholar

• 131

  SongL.HuangY.HouX.YangY.KalaS.QiuZ.et al (2018). PINK1/Parkin-Mediated mitophagy promotes resistance to sonodynamic therapy. Cell. Physiol. biochem.49 (5), 1825–1839. 10.1159/000493629

  • CrossRef
  • Google Scholar

• 132

  Song ShenX. G.WuL.WangM.Wangb. X.WangX.KongF.et al (2014). Fenfen Kong, Haijun Shen, Meng Xie, Yanru Ge and Yi JinDual-core@shell-structured Fe3O4–NaYF4@TiO2 nanocomposites as a magnetic targeting drug carrier for bioimaging and combined chemosonodynamic therapy. J. Mat. Chem. B2, 5775–5784. 10.1039/C4TB00841C

  • CrossRef
  • Google Scholar

• 133

  SuX.WangP.YangS.ZhangK.LiuQ.WangX.et al (2015). Sonodynamic therapy induces the interplay between apoptosis and autophagy in K562 cells through ROS.Int. J. Biochem. Cell Biol.60, 82–92. 10.1016/j.biocel.2014.12.023

  • CrossRef
  • Google Scholar

• 134

  SuiX.ChenR.WangZ.HuangZ.KongN.ZhangM.et al (2013). Autophagy and chemotherapy resistance: A promising therapeutic target for cancer treatment. Cell Death Dis.4 (10), e838. 10.1038/cddis.2013.350

  • CrossRef
  • Google Scholar

• 135

  SuslickK. S.DoktyczS. J.FlintE. B. (1990). On the origin of sonoluminescence and sonochemistry. Ultrasonics28 (5), 280–290. 10.1016/0041-624X(90)90033-K

  • CrossRef
  • Google Scholar

• 136

  SuslickK. S. (1990). Sonochemistry., Sonochemistry. Sci.247(4949), 1439–1445. doi: doi:10.1126/science.247.4949.1439

  • CrossRef
  • Google Scholar

• 137

  SviridovA. P.OsminkinaL. A.KharinA. Y.GongalskyM. B.KarginaJ. V.KudryavtsevA. A.et al (2017). Cytotoxicity control of silicon nanoparticles by biopolymer coating and ultrasound irradiation for cancer theranostic applications. Nanotechnology28 (10), 105102. 10.1088/1361-6528/aa5b7c

  • CrossRef
  • Google Scholar

• 138

  TakahashiY.MeyerkordC. L.HoriT.RunkleK.FoxT. E.KesterM.et al (2011). Bif-1 regulates Atg9 trafficking by mediating the fission of Golgi membranes during autophagy. Autophagy7 (1), 61–73. 10.4161/auto.7.1.14015

  • CrossRef
  • Google Scholar

• 139

  TanX.HuangJ.WangY.HeS.JiaL.ZhuY.et al (2021). Transformable nanosensitizer with tumor microenvironment-activated sonodynamic process and calcium release for enhanced cancer immunotherapy. Angew. Chem. Int. Ed. Engl.60 (25), 14051–14059. 10.1002/anie.202102703

  • CrossRef
  • Google Scholar

• 140

  TanidaI. (2011). Autophagosome formation and molecular mechanism of autophagy. Antioxid. Redox Signal.14 (11), 2201–2214. 10.1089/ars.2010.3482

  • CrossRef
  • Google Scholar

• 141

  TsuboyamaK.Koyama-HondaI.SakamakiY.KoikeM.MorishitaH.MizushimaN.et al (2016). The ATG conjugation systems are important for degradation of the inner autophagosomal membrane. Science354 (6315), 1036–1041. 10.1126/science.aaf6136

  • CrossRef
  • Google Scholar

• 142

  VoglD. T.StadtmauerE. A.TanK. S.HeitjanD. F.DavisL. E.PontiggiaL.et al (2014). Combined autophagy and proteasome inhibition: A phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma. Autophagy10 (8), 1380–1390. 10.4161/auto.29264

  • CrossRef
  • Google Scholar

• 143

  WanG.ChenX.WangH.HouS.WangQ.ChengY.et al (2021). Gene augmented nuclear-targeting sonodynamic therapy via Nrf2 pathway-based redox balance adjustment boosts peptide-based anti-PD-L1 therapy on colorectal cancer. J. Nanobiotechnology19 (1), 347. 10.1186/s12951-021-01094-x

  • CrossRef
  • Google Scholar

• 144

  WanG.LiuY.ShiS.ChenB.WangY.WangH.et al (2016a). Hematoporphyrin and doxorubicin co-loaded nanomicelles for the reversal of drug resistance in human breast cancer cells by combining sonodynamic therapy and chemotherapy. RSC Adv.6 (102), 100361–100372. 10.1039/c6ra22724d

  • CrossRef
  • Google Scholar

• 145

  WanG. Y.LiuY.ChenB. W.LiuY. Y.WangY. S.ZhangN.et al (2016b). Recent advances of sonodynamic therapy in cancer treatment. Cancer Biol. Med.13 (3), 325–338. 10.20892/j.issn.2095-3941.2016.0068

  • CrossRef
  • Google Scholar

• 146

  WangH.WangX.WangP.ZhangK.YangS.LiuQ.et al (2013a). Ultrasound enhances the efficacy of chlorin E6-mediated photodynamic therapy in MDA-MB-231 cells. Ultrasound Med. Biol.39 (9), 1713–1724. 10.1016/j.ultrasmedbio.2013.03.017

  • CrossRef
  • Google Scholar

• 147

  WangL.LiG. Z.CaoL.DongY.WangY.WangS. S.et al (2021a). An ultrasound-driven immune-boosting molecular machine for systemic tumor suppression. Sci. Adv.7 (43), eabj4796. 10.1126/sciadv.abj4796

  • CrossRef
  • Google Scholar

• 148

  WangP.LiC.WangX.XiongW.FengX.LiuQ.et al (2015a). Anti-metastatic and pro-apoptotic effects elicited by combination photodynamic therapy with sonodynamic therapy on breast cancer both in vitro and in vivo. Ultrason. Sonochem.23, 116–127. 10.1016/j.ultsonch.2014.10.027

  • CrossRef
  • Google Scholar

• 149

  WangP.WangX.MaL.SahiS.LiL.WangX. B.et al (2018). Nanosonosensitization by using copper-cysteamine nanoparticles augmented sonodynamic cancer treatment. Part. Part. Syst. Charact.35 (4), 1700378. 10.1002/ppsc.201700378

  • CrossRef
  • Google Scholar

• 150

  WangX.JiaY.SuX.WangP.ZhangK.FengX.et al (2015b). Combination of protoporphyrin IX-mediated sonodynamic treatment with doxorubicin synergistically induced apoptotic cell death of a multidrug-resistant leukemia K562/DOX cell line. Ultrasound Med. Biol.41 (10), 2731–2739. 10.1016/j.ultrasmedbio.2015.06.001

  • CrossRef
  • Google Scholar

• 151

  WangX.LiuQ.WangZ.WangP.ZhaoP.ZhaoX.et al (2010a). Role of autophagy in sonodynamic therapy-induced cytotoxicity in S180 cells. Ultrasound Med. Biol.36 (11), 1933–1946. 10.1016/j.ultrasmedbio.2010.06.022

  • CrossRef
  • Google Scholar

• 152

  WangX.LiuQ.WangZ.WangP.ZhaoP.ZhaoX.et al (2010b). Role of autophagy in sonodynamic therapy-induced cytotoxicity in s180 cells. Ultrasound Med. Biol.36 (11), 1933–1946. 10.1016/j.ultrasmedbio.2010.06.022

  • CrossRef
  • Google Scholar

• 153

  WangX.WangP.ZhangK.SuX.HouJ.LiuQ.et al (2013b). Initiation of autophagy and apoptosis by sonodynamic therapy in murine leukemia L1210 cells. Toxicol. Vitro27 (4), 1247–1259. 10.1016/j.tiv.2012.12.023

  • CrossRef
  • Google Scholar

• 154

  WangX.WangX.YueQ.XuH.ZhongX.SunL.et al (2021b). Liquid exfoliation of TiN nanodots as novel sonosensitizers for photothermal-enhanced sonodynamic therapy against cancer. Nano Today39, 101170. 10.1016/j.nantod.2021.101170

  • CrossRef
  • Google Scholar

• 155

  WangX.WangY.WangP.ChengX.LiuQ. (2011). Sonodynamically induced anti-tumor effect with protoporphyrin IX on hepatoma-22 solid tumor. Ultrasonics51 (5), 539–546. 10.1016/j.ultras.2010.12.001

  • CrossRef
  • Google Scholar

• 156

  WangZ.BaiJ.LiF.DuY.WenS.HuK.et al (2003). Study of a "biological focal region" of high-intensity focused ultrasound. Ultrasound Med. Biol.29 (5), 749–754. 10.1016/s0301-5629(02)00785-8

  • CrossRef
  • Google Scholar

• 157

  WangZ.LiuC.ZhaoY.HuM.MaD.ZhangP.et al (2019). Photomagnetic nanoparticles in dual-modality imaging and photo-sonodynamic activity against bacteria. Chem. Eng. J.356, 811–818. 10.1016/j.cej.2018.09.077

  • CrossRef
  • Google Scholar

• 158

  WhiteE.MehnertJ. M.ChanC. S. (2015). Autophagy, metabolism, and cancer. Clin. Cancer Res.21 (22), 5037–5046. 10.1158/1078-0432.ccr-15-0490

  • CrossRef
  • Google Scholar

• 159

  WuP.SunY.DongW.ZhouH.GuoS.ZhangL.et al (2019). Enhanced anti-tumor efficacy of hyaluronic acid modified nanocomposites combined with sonochemotherapy against subcutaneous and metastatic breast tumors. Nanoscale11 (24), 11470–11483. 10.1039/c9nr01691k

  • CrossRef
  • Google Scholar

• 160

  WuY.LiuX.QinZ.HuL.WangX. (2018). Low-frequency ultrasound enhances chemotherapy sensitivity and induces autophagy in PTX-resistant PC-3 cells via the endoplasmic reticulum stress-mediated PI3K/Akt/mTOR signaling pathway. Onco. Targets. Ther.11, 5621–5630. 10.2147/ott.s176744

  • CrossRef
  • Google Scholar

• 161

  XiaoZ.ZhuangB.ZhangG.LiM.JinY. (2021). Pulmonary delivery of cationic liposomal hydroxycamptothecin and 5-aminolevulinic acid for chemo-sonodynamic therapy of metastatic lung cancer. Int. J. Pharm.601, 120572. 10.1016/j.ijpharm.2021.120572

  • CrossRef
  • Google Scholar

• 162

  XiaohuaiW.LewisT. J.MitchellD. (2008). The tumoricidal effect of sonodynamic therapy (SDT) on S-180 sarcoma in mice. Integr. Cancer Ther.7 (2), 96–102. 10.1177/1534735408319065

  • CrossRef
  • Google Scholar

• 163

  XiongJ.JiangB.LuoY.ZouJ.GaoX.XuD.et al (2020). Multifunctional nanoparticles encapsulating Astragalus polysaccharide and gold nanorods in combination with focused ultrasound for the treatment of breast cancer. Int. J. Nanomedicine15, 4151–4169. 10.2147/IJN.S246447

  • CrossRef
  • Google Scholar

• 164

  XuF.HuM.LiuC.ChoiS. K. (2017). Yolk-structured multifunctional up-conversion nanoparticles for synergistic photodynamic–sonodynamic antibacterial resistance therapy. Biomater. Sci.5 (4), 678–685. 10.1039/c7bm00030h

  • CrossRef
  • Google Scholar

• 165

  XuH.YuN.ZhangJ.WangZ.GengP.WenM.et al (2020a). Biocompatible Fe-Hematoporphyrin coordination nanoplatforms with efficient sonodynamic-chemo effects on deep-seated tumors. Biomaterials257, 120239. 10.1016/j.biomaterials.2020.120239

  • CrossRef
  • Google Scholar

• 166

  XuP.YaoJ.LiZ.WangM.ZhouL.ZhongG.et al (2020b). Therapeutic effect of doxorubicin-chlorin E6-loaded mesoporous silica nanoparticles combined with ultrasound on triple-negative breast cancer. Int. J. Nanomedicine15, 2659–2668. 10.2147/ijn.s243037

  • CrossRef
  • Google Scholar

• 167

  XueL. Y.ChiuS. M.AzizuddinK.JosephS.OleinickN. L. (2007). The death of human cancer cells following photodynamic therapy: Apoptosis competence is necessary for bcl-2 protection but not for induction of autophagy. Photochem. Photobiol.83 (5), 1016–1023. 10.1111/j.1751-1097.2007.00159.x

  • CrossRef
  • Google Scholar

• 168

  YangZ.TaoD.ZhongW.LiuZ.FengL.ChenM.et al (2022). Perfluorocarbon loaded fluorinated covalent organic polymers with effective sonosensitization and tumor hypoxia relief enable synergistic sonodynamic-immunotherapy. Biomaterials280, 121250. 10.1016/j.biomaterials.2021.121250

  • CrossRef
  • Google Scholar

• 169

  YeJ.FuQ.LiuL.ChenL.ZhangX.LiQ.et al (2021). Ultrasound-propelled Janus Au NR-mSiO2 nanomotor for NIR-II photoacoustic imaging guided sonodynamic-gas therapy of large tumors. Sci. China Chem.64 (12), 2218–2229. 10.1007/s11426-021-1070-6

  • CrossRef
  • Google Scholar

• 170

  YimW. W.MizushimaN. (2020). Lysosome biology in autophagy. Cell Discov.6, 6. 10.1038/s41421-020-0141-7

  • CrossRef
  • Google Scholar

• 171

  YinH.ChangN.XuS.WanM. (2016). Sonoluminescence characterization of inertial cavitation inside a BSA phantom treated by pulsed HIFU. Ultrason. Sonochem.32, 158–164. 10.1016/j.ultsonch.2016.02.025

  • CrossRef
  • Google Scholar

• 172

  YinY.JiangX.SunL.LiH.SuC.ZhangY.et al (2021). Continuous inertial cavitation evokes massive ROS for reinforcing sonodynamic therapy and immunogenic cell death against breast carcinoma. Nano Today36, 101009. 10.1016/j.nantod.2020.101009

  • CrossRef
  • Google Scholar

• 173

  YuZ.CaoW.HanC.WangZ.QiuY.WangJ.et al (2022). Biomimetic metal-organic framework nanoparticles for synergistic combining of SDT-chemotherapy induce pyroptosis in gastric cancer. Front. Bioeng. Biotechnol.10, 796820. 10.3389/fbioe.2022.796820

  • CrossRef
  • Google Scholar

• 174

  YuanF.YangC.ZhongP. (2015). Cell membrane deformation and bioeffects produced by tandem bubble-induced jetting flow. Proc. Natl. Acad. Sci. U. S. A.112 (51), E7039–E7047. 10.1073/pnas.1518679112

  • CrossRef
  • Google Scholar

• 175

  YuanY. G.GurunathanS. (2017). Combination of graphene oxide-silver nanoparticle nanocomposites and cisplatin enhances apoptosis and autophagy in human cervical cancer cells. Int. J. Nanomedicine12, 6537–6558. 10.2147/ijn.s125281

  • CrossRef
  • Google Scholar

• 176

  YueW. W.ChenL.YuL. D.ZhouB. G.YinH. H.RenW. W.et al (2019). Checkpoint blockade and nanosonosensitizer- augmented noninvasive sonodynamic therapy combination reduces tumour growth and metastases in mice. Nat. Com.10. 10.1038/s41467-019-09760-3

  • CrossRef
  • Google Scholar

• 177

  YumitaN.NishigakiR.UmemuraK.UmemuraS. (1989). Hematoporphyrin as a sensitizer of cell-damaging effect of ultrasound. Jpn. J. Cancer Res.80 (3), 219–222. 10.1111/j.1349-7006.1989.tb02295.x

  • CrossRef
  • Google Scholar

• 178

  YumitaN.OkuyamaN.SasakiK.UmemuraS. (2007). Sonodynamic therapy on chemically induced mammary tumor: Pharmacokinetics, tissue distribution and sonodynamically induced antitumor effect of gallium-porphyrin complex ATX-70. Cancer Chemother. Pharmacol.60 (6), 891–897. 10.1007/s00280-007-0436-5

  • CrossRef
  • Google Scholar

• 179

  YumitaN.OkuyamaN.SasakiK.UmemuraS. (2004). Sonodynamic therapy on chemically induced mammary tumor: Pharmacokinetics, tissue distribution and sonodynamically induced antitumor effect of porfimer sodium. Cancer Sci.95 (9), 765–769. 10.1111/j.1349-7006.2004.tb03259.x

  • CrossRef
  • Google Scholar

• 180

  YunC. W.LeeS. H. (2018). The roles of autophagy in cancer. Int. J. Mol. Sci.19 (11), E3466. 10.3390/ijms19113466

  • CrossRef
  • Google Scholar

• 181

  ZachariM.GanleyI. G. (2017). The mammalian ULK1 complex and autophagy initiation. Essays Biochem.61 (6), 585–596. 10.1042/ebc20170021

  • CrossRef
  • Google Scholar

• 182

  ZengX.ZhaoH.LiY.FanJ.SunY.WangS.et al (2015). Targeting Hedgehog signaling pathway and autophagy overcomes drug resistance of BCR-ABL-positive chronic myeloid leukemia. Autophagy11 (2), 355–372. 10.4161/15548627.2014.994368

  • CrossRef
  • Google Scholar

• 183

  ZhangH.RenY.CaoF.ChenJ.ChenC.ChangJ.et al (2019a). In situ autophagy disruption generator for cancer theranostics. ACS Appl. Mat. Interfaces11 (33), 29641–29654. 10.1021/acsami.9b10578

  • CrossRef
  • Google Scholar

• 184

  ZhangJ.ShiC.ShanF.ShiN.YeW.ZhuoY.et al (2021a). From biology to biology: Hematoporphyrin-melanin nanoconjugates with synergistic sonodynamic-photothermal effects on malignant tumors. Chem. Eng. J.408, 127282. 10.1016/j.cej.2020.127282

  • CrossRef
  • Google Scholar

• 185

  ZhangL.YiH.SongJ.HuangJ.YangK.TanB.et al (2019b). Mitochondria-targeted and ultrasound-activated nanodroplets for enhanced deep-penetration sonodynamic cancer therapy. ACS Appl. Mat. Interfaces11 (9), 9355–9366. 10.1021/acsami.8b21968

  • CrossRef
  • Google Scholar

• 186

  ZhangQ.WangW.ShenH.TaoH.WuY.MaL.et al (2021b). Low-intensity focused ultrasound-augmented multifunctional nanoparticles for integrating ultrasound imaging and synergistic therapy of metastatic breast cancer. Nanoscale Res. Lett.16 (1), 73. 10.1186/s11671-021-03532-z

  • CrossRef
  • Google Scholar

• 187

  ZhangR. Y.ChengK.XuanY.YangX. Q.AnJ.HuY. G.et al (2021c). A pH/ultrasonic dual-response step-targeting enterosoluble granule for combined sonodynamic-chemotherapy guided via gastrointestinal tract imaging in orthotopic colorectal cancer. Nanoscale13 (7), 4278–4294. 10.1039/d0nr08100k

  • CrossRef
  • Google Scholar

• 188

  ZhangY.KangS.LinH.ChenM.LiY.CuiL.et al (2022). Regulation of zeolite-derived upconversion photocatalytic system for near infrared light/ultrasound dual-triggered multimodal melanoma therapy under a boosted hypoxia relief tumor microenvironment via autophagy. Chem. Eng. J.429, 132484. 10.1016/j.cej.2021.132484

  • CrossRef
  • Google Scholar

• 189

  ZhaoY. G.CodognoP.ZhangH. (2021). Machinery, regulation and pathophysiological implications of autophagosome maturation. Nat. Rev. Mol. Cell Biol.22 (11), 733–750. 10.1038/s41580-021-00392-4

  • CrossRef
  • Google Scholar

• 190

  ZhaoY.HuM.ZhangY.LiuJ.LiuC.ChoiS. K.et al (2020). Multifunctional therapeutic strategy of Ag-synergized dual-modality upconversion nanoparticles to achieve the rapid and sustained cidality of methicillin-resistant Staphylococcus aureus. Chem. Eng. J.385, 123980. 10.1016/j.cej.2019.123980

  • CrossRef
  • Google Scholar

• 191

  ZhengY.LiZ.YangY.ShiH.ChenH.GaoY.et al (2021a). A nanosensitizer self-assembled from oleanolic acid and chlorin e6 for synergistic chemo/sono-photodynamic cancer therapy. Phytomedicine.93, 153788. 10.1016/j.phymed.2021.153788

  • CrossRef
  • Google Scholar

• 192

  ZhengY.LiuY.WeiF.XiaoH.MouJ.WuH.et al (2021b). Functionalized g-C3N4 nanosheets for potential use in magnetic resonance imaging-guided sonodynamic and nitric oxide combination therapy. Acta Biomater.121, 592–604. 10.1016/j.actbio.2020.12.011

  • CrossRef
  • Google Scholar

• 193

  ZhongX. Y.WangX. W.ChengL.TangY. A.ZhanG. T.GongF.et al (2020). GSH-depleted PtCu3 nanocages for chemodynamic- enhanced sonodynamic cancer therapy. Adv. Funct. Mat.30 (4), 1907954. 10.1002/adfm.201907954

  • CrossRef
  • Google Scholar

• 194

  ZhouL.HuoM.QianX.DingL.YuL.FengW.et al (2021). Autophagy blockade synergistically enhances nanosonosensitizer-enabled sonodynamic cancer nanotherapeutics. J. Nanobiotechnology19 (1), 112. 10.1186/s12951-021-00855-y

  • CrossRef
  • Google Scholar

• 195

  ZhuJ.OuyangA.HeJ.XieJ.BanerjeeS.ZhangQ.et al (2022). An ultrasound activated cyanine-rhenium(I) complex for sonodynamic and gas synergistic therapy. Chem. Commun.58 (20), 3314–3317. 10.1039/d1cc06769a

  • CrossRef
  • Google Scholar

• 196

  ZhuP.ChenY.ShiJ. (2020a). Piezocatalytic tumor therapy by ultrasound-triggered and BaTiO(3) -mediated piezoelectricity. Adv. Mat.32 (29), e2001976. 10.1002/adma.202001976

  • CrossRef
  • Google Scholar

• 197

  ZhuW.ChenQ.JinQ.ChaoY.SunL.HanX.et al (2020b). Sonodynamic therapy with immune modulatable two-dimensional coordination nanosheets for enhanced anti-tumor immunotherapy. Nano Res.14 (1), 212–221. 10.1007/s12274-020-3070-8

  • CrossRef
  • Google Scholar

• 198

  ZouW.HaoJ.WuJ.CaiX.HuB.WangZ.et al (2021). Biodegradable reduce expenditure bioreactor for augmented sonodynamic therapy via regulating tumor hypoxia and inducing pro-death autophagy. J. Nanobiotechnology19 (1), 418. 10.1186/s12951-021-01166-y

  • CrossRef
  • Google Scholar

• 199

  ZuoS.ZhangY.WangZ.WangJ. (2022). Mitochondria-targeted mesoporous titanium dioxide nanoplatform for synergistic nitric oxide gas-sonodynamic therapy of breast cancer. Int. J. Nanomedicine17, 989–1002. 10.2147/IJN.S348618

  • CrossRef
  • Google Scholar