Sonodynamic therapy for malignant tumours has gained much attention for its deep penetration effect and efficient tumour killing ability.The design,modification,and utilization of sonosensitizers are important aspects...Sonodynamic therapy for malignant tumours has gained much attention for its deep penetration effect and efficient tumour killing ability.The design,modification,and utilization of sonosensitizers are important aspects of sonodynamic therapy.As an essential factor in this process,highly effective sonosensitizers should be developed to facilitate the clinical applications of sonodynamic therapy.This review takes porphyrin-and titanium dioxide(TiO_(2))-based systems as representative organic and inorganic sonosensitizers respectively,and summarizes their characteristics and biological effects as sonodynamic therapy.Upon discovery of novel sonosensitizers,sonodynamic therapy becomes an efficient means of adjuvant therapy for the treatment of malignant tumours.展开更多
Glioblastoma multiforme(GBM) is the most common primary malignant brain tumor, and it is associated with poor prognosis. Its characteristics of being highly invasive and undergoing heterogeneous genetic mutation, as w...Glioblastoma multiforme(GBM) is the most common primary malignant brain tumor, and it is associated with poor prognosis. Its characteristics of being highly invasive and undergoing heterogeneous genetic mutation, as well as the presence of the blood–brain barrier(BBB), have reduced the efficacy of GBM treatment. The emergence of a novel therapeutic method, namely, sonodynamic therapy(SDT), provides a promising strategy for eradicating tumors via activated sonosensitizers coupled with low-intensity ultrasound. SDT can provide tumor killing effects for deep-seated tumors, such as brain tumors. However, conventional sonosensitizers cannot effectively reach the tumor region and kill additional tumor cells, especially brain tumor cells. Efforts should be made to develop a method to help therapeutic agents pass through the BBB and accumulate in brain tumors. With the development of novel multifunctional nanosensitizers and newly emerging combination strategies, the killing ability and selectivity of SDT have greatly improved and are accompanied with fewer side effects. In this review, we systematically summarize the findings of previous studies on SDT for GBM, with a focus on recent developments and promising directions for future research.展开更多
In recent years,because of the growing desire to improve the noninvasiveness and safety of tumor treatments,sonodynamic therapy has gradually become a popular research topic.However,due to the complexity of the therap...In recent years,because of the growing desire to improve the noninvasiveness and safety of tumor treatments,sonodynamic therapy has gradually become a popular research topic.However,due to the complexity of the therapeutic process,the relevant mechanisms have not yet been fully elucidated.One of the widely accepted possibilities involves the effect of reactive oxygen species.In this review,the mechanism of reactive oxygen species production by sonodynamic therapy(SDT)and ways to enhance the sonodynamic production of reactive oxygen species are reviewed.Then,the clinical application and limitations of SDT are discussed.In conclusion,current research on sonodynamic therapy should focus on the development of sonosensitizers that efficiently produce active oxygen,exhibit biological safety,and promote the clinical transformation of sonodynamic therapy.展开更多
Sonodynamic therapy(SDT) is an emerging approach that involves a combination of low-intensity ultrasound and specialized chemical agents known as sonosensitizers. Ultrasound can penetrate deeply into tissues and can b...Sonodynamic therapy(SDT) is an emerging approach that involves a combination of low-intensity ultrasound and specialized chemical agents known as sonosensitizers. Ultrasound can penetrate deeply into tissues and can be focused into a small region of a tumor to activate a sonosensitizer which offers the possibility of non-invasively eradicating solid tumors in a site-directed manner.In this article, we critically reviewed the currently accepted mechanisms of sonodynamic action and summarized the classification of sonosensitizers. At the same time, the breath of evidence from SDT-based studies suggests that SDT is promising for cancer treatment.展开更多
Sonodynamic therapy is a new cancer treatment based on the synergetic effect of ultrasound and a drug. In this study, ultrasonically induced antitumor effects of benzoporphyrin derivative monoacid ring A (BPD-MA) on K...Sonodynamic therapy is a new cancer treatment based on the synergetic effect of ultrasound and a drug. In this study, ultrasonically induced antitumor effects of benzoporphyrin derivative monoacid ring A (BPD-MA) on KLN205 cells were investigated. KLN205 cells were irradiated at an ultrasonic frequency of 3 MHz with 10 μg/ml BPD-MA. The ultrasonically induced cell damage significantly increased as an ultrasonic intensity and ultrasound exposure time increased. Confocal microscopic examination revealed that the irradiated cells were induced chromatin condensation and phosphatidylserine exposure. The synergistic effect of the ultrasound exposure and BPD-MA on the tumor cell adhesion rate was significant.展开更多
Reactive oxygen species(ROS),involving in many biological reactions,play an important role in disease treatment.Among the various ROS-based therapeutic modalities,sonodynamic therapy(SDT)stands out with its unique adv...Reactive oxygen species(ROS),involving in many biological reactions,play an important role in disease treatment.Among the various ROS-based therapeutic modalities,sonodynamic therapy(SDT)stands out with its unique advantages.In turn,the SDT efficacy is mainly dependent on the ROS levels in the disease microenvironment.Therefore,in recent years,researchers have extensively investigated SDT with high ROS generation capacity.In this review,we focus on effective strategies to improve the therapeutic ef-ficiency of SDT by modulating ROS,overview the basic mechanisms of ROS generation by sonosensitizers,highlight the rational design of sonosensitizers,and summarize strategies to improve the SDT efficacy by modulating disease microenvironment.In addition,multiple ROS synergistic treatment modalities and the prospect of SDT are discussed.We believe that the understanding and exploration of SDT enhancement strategies will facilitate the clinical translation of SDT.展开更多
Ultrasound(US)-activated sonodynamic therapy(SDT)stands for a distinct antitumor modality because of its attractive characteristics including intriguing noninvasiveness,desirable safety,and high tissue penetration dep...Ultrasound(US)-activated sonodynamic therapy(SDT)stands for a distinct antitumor modality because of its attractive characteristics including intriguing noninvasiveness,desirable safety,and high tissue penetration depth,which,unfortunately,suffers from compromised therapeutic efficacy due to cancer cell-inherent adaptive mechanisms,such as glutathione(GSH)neutralization response to reactive oxygen species(ROS),and glutamine addictive properties of tumors.In this work,we developed a biological sonosensitive platelet(PLT)pharmacytes for favoring US/GSH-responsive combinational therapeutic of glutamine deprivation and augmented SDT.The amino acid transporter SLC6A14 blockade agentα-methyl-DL-tryptophan(α-MT)-loaded and MnO_(2)-coated porphyrinic metal-organic framework(MOF)nanoparticles were encapsulated in the PLTs through the physical adsorption of electrostatic attraction and the intrinsic endocytosis of PLTs.When the sonosensitive PLT pharmacytes reached tumor sites through their natural tendencies to TME,US stimulated the PLTs-loaded porphyrinic MOF to generate ROS,resulting in morphological changes of the PLTs and the release of nanoparticles.Subsequently,intracellular high concentration of GSH and extracellular spatio-temporal controlled US irradiation programmatically triggered the release ofα-MT,which enabled the synergistically amplified SDT by inducing amino acid starvation,inhibiting mTOR,and mediating ferroptosis.In addition,US stimulation achieved the targeted activation of PLTs at tumor vascular site,which evolved from circulating PLTs to dendritic PLTs,effectively blocking the blood supply of tumors through thrombus formation,and revealing the encouraging potential to facilitate tumor therapeutics.展开更多
Sonodynamic therapy(SDT),as a novel non-invasive strategy for eliminating tumor,has the advantages of deeper tissue penetration,fewer side effects,and better patient compliance,compared with photodynamic therapy(PDT)....Sonodynamic therapy(SDT),as a novel non-invasive strategy for eliminating tumor,has the advantages of deeper tissue penetration,fewer side effects,and better patient compliance,compared with photodynamic therapy(PDT).In SDT,ultrasound was used to activate sonosensitizer to produce cytotoxic reactive oxygen species(ROS),induce the collapse of vacuoles in solution,and bring about irreversible damage to cancer cells.In recent years,much effort has been devoted to developing highly efficient sonosensitizers which can efficiently generate ROS.However,the traditional organic sonosensitizers,such as porphyrins,hypericin,and curcumins,suffer from complex synthesis,poor water solubility,and low tumor targeting efficacy which limit the benefits of SDT.In contrast,inorganic sonosensitizers show good in vivo stability,controllable physicochemical properties,ease of achieving multifunctionality,and high tumor targeting,which greatly expanded their application in SDT.In this review,we systematically summarize the nanomaterials which act as the carrier of molecular sonosensitizers,and directly produce ROS under ultrasound.Moreover,the prospects of inorganic nanomaterials for SDT application are also discussed.展开更多
Sonodynamic therapy(SDT)has attracted widespread interest in biomedicine,owing to its novel and noninvasive therapeutic method triggered by ultrasound(US).Herein,the Ti_(3)C_(2) MXene nanosheets(Ti_(3)C_(2) NSs)are de...Sonodynamic therapy(SDT)has attracted widespread interest in biomedicine,owing to its novel and noninvasive therapeutic method triggered by ultrasound(US).Herein,the Ti_(3)C_(2) MXene nanosheets(Ti_(3)C_(2) NSs)are developed as good sonosensitizers via a two-step method of chemical exfoliation and high-temperature treatment.With the high-temperature treatment,the oxygen defect of Ti_(3)C_(2) MXene nanosheets(H-Ti_(3)C_(2) NSs)is greatly increased.Therefore,the electron(e^(-))and hole(h^(+))generated by US can be separated faster due to the improved degree of oxidation,and then the recombination of e^(-)-h^(+)can be prevented with the abundant oxygen defect under US irradiation,which induced the sonodynamic efficiency greatly to improve around 3.7-fold compared with Ti_(3)C_(2) NSs without high-temperature treatment.After PEGylation,the H-Ti_(3)C_(2)-PEG NSs show good stability and biocompatibility.In vitro studies exhibit that the inherent property of mild photothermal effect can promote the endocytosis of H-Ti_(3)C_(2)-PEG NSs,which can improve the SDT efficacy.In vivo studies further display that the increased blood supply by the mild photothermal effect can significantly relieve hypoxia in the tumor microenvironment,showing photothermal therapy(PTT)enhanced SDT.Most importantly,the H-Ti_(3)C_(2)-PEG NSs can be biodegraded and excreted out of the body,showing no significant long-term toxicity.Our work develops the defective H-Ti_(3)C_(2) NSs as high-efficiency and safe sonosensitizers for photothermal-enhanced SDT of cancer,extending the biomedical application of MXene-based nanoplatforms.展开更多
Sonodynamic therapy(SDT)has aroused considerable momentum in cancer therapy due to its abilities of deep penetration,low toxicity,and noninvasion,while insufficient tumor accumulation of sonosensitizers is a major obs...Sonodynamic therapy(SDT)has aroused considerable momentum in cancer therapy due to its abilities of deep penetration,low toxicity,and noninvasion,while insufficient tumor accumulation of sonosensitizers is a major obstacle for SDT effect.Here,we developed a 4T1 cancer cell-macrophage hybrid membrane(HM)-camouflaged sonosensitizer nanoplatform by encapsulating photochlor(HPPH)-loaded albumin nanoparticles(PHNPs).The experimental results proved that the HM-coated biomimetic NPs(PHNPs@HM)could express the characteristic membrane proteins of both cancer cells and macrophages,remarkedly enhancing the effective targeting and endocytosis to 4T1 cells through homologous adhesion recognition and immune escaping.Meanwhile,as a novel sonosensitizer,HPPH could generate amount of reactive oxygen species(ROS)under ultrasound(US)irradiation and exhibit obvious SDT efficiency to inhibit 4T1 tumor growth through ROS-induced cell apoptosis.This study provides a novel and multifunctional biomimetic sonosensitizer system to enhance SDT efficiency.展开更多
基金This work was supported by the National Key Research and Development Program of China(No.2016YFC1100100)the Singapore National Research Foundation Investigatorship(No.NRF-NRFI2018-03).
文摘Sonodynamic therapy for malignant tumours has gained much attention for its deep penetration effect and efficient tumour killing ability.The design,modification,and utilization of sonosensitizers are important aspects of sonodynamic therapy.As an essential factor in this process,highly effective sonosensitizers should be developed to facilitate the clinical applications of sonodynamic therapy.This review takes porphyrin-and titanium dioxide(TiO_(2))-based systems as representative organic and inorganic sonosensitizers respectively,and summarizes their characteristics and biological effects as sonodynamic therapy.Upon discovery of novel sonosensitizers,sonodynamic therapy becomes an efficient means of adjuvant therapy for the treatment of malignant tumours.
基金partially supported by the National Natural Science Foundation of China(81702457)the Clinical Medical University and Hospital Joint Construction of Disciplinary Projects 2021(2021lcxk017)+4 种基金the Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer(2020B121201004)the Outstanding Youths Development Scheme of Nanfang Hospital,Southern Medical University(2021J008)the Basic and Clinical Cooperative Research and Promotion Program of Anhui Medical University(2021xkjT028)the Open Fund of Key Laboratory of Antiinflammatory and Immune Medicine(KFJJ-2021-11)Grants for Scientific Research of BSKY from Anhui Medical University(1406012201)。
文摘Glioblastoma multiforme(GBM) is the most common primary malignant brain tumor, and it is associated with poor prognosis. Its characteristics of being highly invasive and undergoing heterogeneous genetic mutation, as well as the presence of the blood–brain barrier(BBB), have reduced the efficacy of GBM treatment. The emergence of a novel therapeutic method, namely, sonodynamic therapy(SDT), provides a promising strategy for eradicating tumors via activated sonosensitizers coupled with low-intensity ultrasound. SDT can provide tumor killing effects for deep-seated tumors, such as brain tumors. However, conventional sonosensitizers cannot effectively reach the tumor region and kill additional tumor cells, especially brain tumor cells. Efforts should be made to develop a method to help therapeutic agents pass through the BBB and accumulate in brain tumors. With the development of novel multifunctional nanosensitizers and newly emerging combination strategies, the killing ability and selectivity of SDT have greatly improved and are accompanied with fewer side effects. In this review, we systematically summarize the findings of previous studies on SDT for GBM, with a focus on recent developments and promising directions for future research.
基金the National Natural Science Foundation of China,No.82272004 and No.81974470the Nature Science Foundation of Zhejiang Province,No.LZ22H180001.
文摘In recent years,because of the growing desire to improve the noninvasiveness and safety of tumor treatments,sonodynamic therapy has gradually become a popular research topic.However,due to the complexity of the therapeutic process,the relevant mechanisms have not yet been fully elucidated.One of the widely accepted possibilities involves the effect of reactive oxygen species.In this review,the mechanism of reactive oxygen species production by sonodynamic therapy(SDT)and ways to enhance the sonodynamic production of reactive oxygen species are reviewed.Then,the clinical application and limitations of SDT are discussed.In conclusion,current research on sonodynamic therapy should focus on the development of sonosensitizers that efficiently produce active oxygen,exhibit biological safety,and promote the clinical transformation of sonodynamic therapy.
基金supported by the National Natural Science Foundation of China(Grant No.81573005 and 81371671)
文摘Sonodynamic therapy(SDT) is an emerging approach that involves a combination of low-intensity ultrasound and specialized chemical agents known as sonosensitizers. Ultrasound can penetrate deeply into tissues and can be focused into a small region of a tumor to activate a sonosensitizer which offers the possibility of non-invasively eradicating solid tumors in a site-directed manner.In this article, we critically reviewed the currently accepted mechanisms of sonodynamic action and summarized the classification of sonosensitizers. At the same time, the breath of evidence from SDT-based studies suggests that SDT is promising for cancer treatment.
文摘Sonodynamic therapy is a new cancer treatment based on the synergetic effect of ultrasound and a drug. In this study, ultrasonically induced antitumor effects of benzoporphyrin derivative monoacid ring A (BPD-MA) on KLN205 cells were investigated. KLN205 cells were irradiated at an ultrasonic frequency of 3 MHz with 10 μg/ml BPD-MA. The ultrasonically induced cell damage significantly increased as an ultrasonic intensity and ultrasound exposure time increased. Confocal microscopic examination revealed that the irradiated cells were induced chromatin condensation and phosphatidylserine exposure. The synergistic effect of the ultrasound exposure and BPD-MA on the tumor cell adhesion rate was significant.
基金supported by the National Key Research and Development Program of China(No.2021YFC2102900)the National Natural Science Foundation of China(Nos.U21A2085,22061130205)+1 种基金the Joint Project of BRC-BC(Biomedical Translational Engineering Research Center of BUCT-CJFH)(No.XK2022-O8)the Open Foundation of State Key Laboratory of Organic-Inorganic Composites,Beijing University of Chemical Technology(No.OIC-202201010).
文摘Reactive oxygen species(ROS),involving in many biological reactions,play an important role in disease treatment.Among the various ROS-based therapeutic modalities,sonodynamic therapy(SDT)stands out with its unique advantages.In turn,the SDT efficacy is mainly dependent on the ROS levels in the disease microenvironment.Therefore,in recent years,researchers have extensively investigated SDT with high ROS generation capacity.In this review,we focus on effective strategies to improve the therapeutic ef-ficiency of SDT by modulating ROS,overview the basic mechanisms of ROS generation by sonosensitizers,highlight the rational design of sonosensitizers,and summarize strategies to improve the SDT efficacy by modulating disease microenvironment.In addition,multiple ROS synergistic treatment modalities and the prospect of SDT are discussed.We believe that the understanding and exploration of SDT enhancement strategies will facilitate the clinical translation of SDT.
基金supported by the Science and Technology Development Fund,Macao SAR(Grant No.0114/2019/A2,0085/2020/A2)the Research Grant of University of Macao(Grant No.MYRG2020-00130-FHS).
文摘Ultrasound(US)-activated sonodynamic therapy(SDT)stands for a distinct antitumor modality because of its attractive characteristics including intriguing noninvasiveness,desirable safety,and high tissue penetration depth,which,unfortunately,suffers from compromised therapeutic efficacy due to cancer cell-inherent adaptive mechanisms,such as glutathione(GSH)neutralization response to reactive oxygen species(ROS),and glutamine addictive properties of tumors.In this work,we developed a biological sonosensitive platelet(PLT)pharmacytes for favoring US/GSH-responsive combinational therapeutic of glutamine deprivation and augmented SDT.The amino acid transporter SLC6A14 blockade agentα-methyl-DL-tryptophan(α-MT)-loaded and MnO_(2)-coated porphyrinic metal-organic framework(MOF)nanoparticles were encapsulated in the PLTs through the physical adsorption of electrostatic attraction and the intrinsic endocytosis of PLTs.When the sonosensitive PLT pharmacytes reached tumor sites through their natural tendencies to TME,US stimulated the PLTs-loaded porphyrinic MOF to generate ROS,resulting in morphological changes of the PLTs and the release of nanoparticles.Subsequently,intracellular high concentration of GSH and extracellular spatio-temporal controlled US irradiation programmatically triggered the release ofα-MT,which enabled the synergistically amplified SDT by inducing amino acid starvation,inhibiting mTOR,and mediating ferroptosis.In addition,US stimulation achieved the targeted activation of PLTs at tumor vascular site,which evolved from circulating PLTs to dendritic PLTs,effectively blocking the blood supply of tumors through thrombus formation,and revealing the encouraging potential to facilitate tumor therapeutics.
基金supported by the National Natural Science Foundation of China(No.61805287)National Science Foundation of Hunan Province,China(No.2019JJ50824)the Fundamental Research Funds for Central Universities of the Central South University(Nos.202045002,2019zzts432 and 2020CX021).
文摘Sonodynamic therapy(SDT),as a novel non-invasive strategy for eliminating tumor,has the advantages of deeper tissue penetration,fewer side effects,and better patient compliance,compared with photodynamic therapy(PDT).In SDT,ultrasound was used to activate sonosensitizer to produce cytotoxic reactive oxygen species(ROS),induce the collapse of vacuoles in solution,and bring about irreversible damage to cancer cells.In recent years,much effort has been devoted to developing highly efficient sonosensitizers which can efficiently generate ROS.However,the traditional organic sonosensitizers,such as porphyrins,hypericin,and curcumins,suffer from complex synthesis,poor water solubility,and low tumor targeting efficacy which limit the benefits of SDT.In contrast,inorganic sonosensitizers show good in vivo stability,controllable physicochemical properties,ease of achieving multifunctionality,and high tumor targeting,which greatly expanded their application in SDT.In this review,we systematically summarize the nanomaterials which act as the carrier of molecular sonosensitizers,and directly produce ROS under ultrasound.Moreover,the prospects of inorganic nanomaterials for SDT application are also discussed.
基金supported by the National Natural Science Foundation of China(U20A20254 and 52072253)the Collaborative Innovation Center of Suzhou Nano Science and Technology,Jiangsu Social Development Project(BE2019658)the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions。
基金partially supported by the National Research Programs of China(2016YFA0201200)the National Natural Science Foundation of China(U20A20254,52072253)+3 种基金Collaborative Innovation Center of Suzhou Nano Science and Technology,a Jiangsu Social Development Project(BE2019658)a Project Funded by the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutionssupported by the Tang Scholarship of Soochow Universitythe fundamental Research Funds for Central Universities(2662019PY024).
文摘Sonodynamic therapy(SDT)has attracted widespread interest in biomedicine,owing to its novel and noninvasive therapeutic method triggered by ultrasound(US).Herein,the Ti_(3)C_(2) MXene nanosheets(Ti_(3)C_(2) NSs)are developed as good sonosensitizers via a two-step method of chemical exfoliation and high-temperature treatment.With the high-temperature treatment,the oxygen defect of Ti_(3)C_(2) MXene nanosheets(H-Ti_(3)C_(2) NSs)is greatly increased.Therefore,the electron(e^(-))and hole(h^(+))generated by US can be separated faster due to the improved degree of oxidation,and then the recombination of e^(-)-h^(+)can be prevented with the abundant oxygen defect under US irradiation,which induced the sonodynamic efficiency greatly to improve around 3.7-fold compared with Ti_(3)C_(2) NSs without high-temperature treatment.After PEGylation,the H-Ti_(3)C_(2)-PEG NSs show good stability and biocompatibility.In vitro studies exhibit that the inherent property of mild photothermal effect can promote the endocytosis of H-Ti_(3)C_(2)-PEG NSs,which can improve the SDT efficacy.In vivo studies further display that the increased blood supply by the mild photothermal effect can significantly relieve hypoxia in the tumor microenvironment,showing photothermal therapy(PTT)enhanced SDT.Most importantly,the H-Ti_(3)C_(2)-PEG NSs can be biodegraded and excreted out of the body,showing no significant long-term toxicity.Our work develops the defective H-Ti_(3)C_(2) NSs as high-efficiency and safe sonosensitizers for photothermal-enhanced SDT of cancer,extending the biomedical application of MXene-based nanoplatforms.
基金This work was supported by the National Natural Science Foundation of China(Nos.81901864,81971749,and 82072064)the Natural Science Foundation of Guangdong Province(Nos.2021A1515010131 and 2019A1515011524)+5 种基金Guangdong Province Universities and Colleges Pearl River Scholar Fund(No.4SG21006G)Shenzhen Science and Technology Program(Nos.JCYJ20170818162259843 and JCYJ20210324115607020)Guangdong Province Universities and Colleges Characteristic Innovation(Nos.2021KTSCX035 and 2021KTSCX036)Special Funds of Scientific Technological Innovation of Undergraduates in Guangdong Province(Nos.pdjh2020b0260 and pdjh2020b0265)Guangdong Medical University PHD Funds(2021),Medical Scientific Research Foundation of Guangdong Province(No.A2021429)Zhuhai Innovation and Entrepreneurship Team Project(No.ZH01110405180056PWC).
文摘Sonodynamic therapy(SDT)has aroused considerable momentum in cancer therapy due to its abilities of deep penetration,low toxicity,and noninvasion,while insufficient tumor accumulation of sonosensitizers is a major obstacle for SDT effect.Here,we developed a 4T1 cancer cell-macrophage hybrid membrane(HM)-camouflaged sonosensitizer nanoplatform by encapsulating photochlor(HPPH)-loaded albumin nanoparticles(PHNPs).The experimental results proved that the HM-coated biomimetic NPs(PHNPs@HM)could express the characteristic membrane proteins of both cancer cells and macrophages,remarkedly enhancing the effective targeting and endocytosis to 4T1 cells through homologous adhesion recognition and immune escaping.Meanwhile,as a novel sonosensitizer,HPPH could generate amount of reactive oxygen species(ROS)under ultrasound(US)irradiation and exhibit obvious SDT efficiency to inhibit 4T1 tumor growth through ROS-induced cell apoptosis.This study provides a novel and multifunctional biomimetic sonosensitizer system to enhance SDT efficiency.