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)is a new non-invasive treatment method,which uses low-intensity ultrasound(US)to activate specific sonosensitizers(SNs)to produce reactive oxygen species(ROS)for therapeutic purposes.However,tr...Sonodynamic therapy(SDT)is a new non-invasive treatment method,which uses low-intensity ultrasound(US)to activate specific sonosensitizers(SNs)to produce reactive oxygen species(ROS)for therapeutic purposes.However,traditional sonosensitizers have the defects of low generation efficiency of ROS and single treatment mode.Therefore,designing sonosensitizers with high efficiency to generate ROS,high stability,and multimodal therapy is an excellent alternative to achieve effective,safe,and intelligent therapy.Heterojunction nanosonosensitizers(NSNs),as novel type of SNs,combine different materials through heterojunction structures to improve the efficiency of ROS generation.In this review,the classification of heterojunction NSNs,the preparation methods and characterization methods of heterojunction NSNs and the possible mechanisms for enhancing SDT were firstly presented,followed by an in-depth discussion of the application of heterojunction NSNs in the treatment of bacterial infections and tumors,with a special emphasis on synergistic enhancement of therapeutic efficacy of heterojunction SNs in combination with different therapeutic models such as gas therapy,immunotherapy and nanocatalytic therapy.Finally,the challenges and perspectives of such heterojunction SNs-supported SDT were outlined and highlighted to facilitate their clinical translation.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
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
Atherosclerosis(AS)is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease,stroke,and peripheral vascular disease.Despite the current treatments,mortality and disabili...Atherosclerosis(AS)is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease,stroke,and peripheral vascular disease.Despite the current treatments,mortality and disability still remain high.Sonodynamic therapy(SDT),a non-invasive and localized methodology,has been developed as a promising new treatment for inhibiting atherosclerotic progression and stabilizing plaques.Promising progress has been made through cell and animal assays,as well as clinical trials.For example,the effect of SDT on apoptosis and autophagy of cells in AS,especially macrophages,and the concept of non-lethal SDT has also been proposed.In this review,we summarize the ultrasonic parameters and known sonosensitizers utilized in SDT for AS;we elaborate on SDT's therapeutic effects and mechanisms in terms of macrophages,T lymphocytes,neovascularization,smooth muscle cells,lipid,extracellular matrix and efferocytosis within plaques;additionally,we discuss the safety of SDT.A comprehensive summary of the confirmed effects of SDT on AS is conducted to establish a framework for future researchers.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
Deep-tissue solid cancer treatment has a poor prognosis,resulting in a very low 5-year patient survival rate.The primary challenges facing solid tumor therapies are accessibility,incomplete surgical removal of tumor t...Deep-tissue solid cancer treatment has a poor prognosis,resulting in a very low 5-year patient survival rate.The primary challenges facing solid tumor therapies are accessibility,incomplete surgical removal of tumor tissue,the resistance of the hypoxic and heterogeneous tumor microenvironment to chemotherapy and radiation,and suffering caused by off-target toxicities.Here,sonodynamic therapy(SDT)is an evolving therapeutic approach that uses low-intensity ultrasound to target deep-tissue solid tumors.The ability of ultrasound to deliver energy safely and precisely into small deep-tissue(>10 cm)volumes makes SDT more effective than conventional photodynamic therapy.While SDT is currently in phase 1/2 clinical trials for glioblastoma multiforme,its use for other solid cancer treatments,such as breast,pancreatic,liver,and prostate cancer,is still in the preclinical stage,with further investigation required to improve its therapeutic efficacy.This review,therefore,focuses on recent advances in SDT cancer treatments.We describe the interaction between ultrasound and sonosensitizer molecules and the associated energy transfer mechanism to malignant cells,which plays a central role in SDT-mediated cell death.Different sensitizers used in clinical and preclinical trials of various cancer treatments are listed,and the critical ultrasound parameters for SDT are reviewed.We also discuss approaches to improve the efficacies of these sonosensitizers,the role of the 3-dimensional spheroid in vitro investigations,ultrasound-controlled CAR-T cell and SDT-based multimodal therapy,and machine learning for sonosensitizer optimization,which could facilitate clinical translation of SDT.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
Natural product(NPT)derived from traditional Chinese medicine has a rich history as an integral part of Chinese healthcare for thousands of years.Recently,the application of NPT in sonodynamic antibacterial therapy(SD...Natural product(NPT)derived from traditional Chinese medicine has a rich history as an integral part of Chinese healthcare for thousands of years.Recently,the application of NPT in sonodynamic antibacterial therapy(SDAT)has emerged as a promising area of research.This perspective summarizes the recent NPT-based sonosensitizers in SDAT.Currently,common NPT-based sonosensitizers include curcumin,chlorophyll derivatives,hypericin,and berberine.Compared with other sonosensitizers,natural sources of NPT-based sonosensitizers with reactive oxide species production performance under ultrasound conditions,low biotoxicity,and other additional biological activity make them have application prospects in bacterial removal.Finally,the potential benefits and challenges of NPT-based nanosonosensitizers were also discussed.展开更多
Immunogenic cell death(ICD)has been demonstrated as a reliable approach to improve therapeutic effect in cancer treatment by triggering antitumor immunity.However,the trigger of ICD on the basis of chemotherapy and ph...Immunogenic cell death(ICD)has been demonstrated as a reliable approach to improve therapeutic effect in cancer treatment by triggering antitumor immunity.However,the trigger of ICD on the basis of chemotherapy and phototherapy meets the obstacles of serious side effect and poor penetration ability,which seriously impedes the therapeutic effect.The development of sonodynamic immunotherapy with the evoking of ICD presents high promise for cancer treatment with high efficacy.Herein,high performance aggregation-induced emission(AIE)sonosensitizer is constructed on the basis of the engineering structure modulation for sonodynamic-augmented immunotherapy.By regulating the intermolecular interaction and pull-push electronic effect,sonosensitizer bearing AIE feature and amplified sono-sensitizing effect is developed.In addition,in vitro observation demonstrated that thiolate-substituted segment incorporation endows the molecules with enhanced cellular uptake efficiency and improved tumor cell eradication ability.More importantly,the developed sonosensitizer could efficiently evoke ICD upon the trigger of ultrasound,which allows for the efficient tumor eradication both at cellular level and in solid tumor.The inhibition of primary tumor and further boost systemic immunity response with the complete elimination toward the distant tumor is achieved.The investigation highlights the promise of utilizing AIE sonosensitizers in sonodynamic immunotherapy to conquer the current limitation of immunotherapy in solid tumor treatment.展开更多
Regulated cell death(RCD)is considered a vital process in cancer therapy,determining treatment outcomes and facilitating the eradication of cancer cells.As an emerging type of RCD,PANoptosis features excellent antineo...Regulated cell death(RCD)is considered a vital process in cancer therapy,determining treatment outcomes and facilitating the eradication of cancer cells.As an emerging type of RCD,PANoptosis features excellent antineoplastic effects due to its combination of death modes,including pyroptosis,apoptosis,and necroptosis.In this work,anion‐cation vacancies(oxygen/titanium‐vacancy‐rich)ultrathin HTiO nanosheets with outstanding sonocatalytic performance and peroxidase‐mimicking activity are rationally engineered for the disruption of mitochondrial function in tumor cells and the destabilization of redox homeostasis,ultimately inducing tumor PANoptosis.The utilization of external ultrasound energy amplifies the production of toxic reactive oxygen species(ROS).Density functional theory calculations indicate that the oxygen and titanium vacancies generated in HTiO nanosheets enhance the ROS generation efficiency by promoting carrier separation and increasing the adsorption capacity of H_(2)O_(2).The advantages of triggering PANoptosis are substantially evidenced by exceptional antineoplastic efficacy both at the cellular level and on two in vivo separate tumor xenografts(4T1 and MDA‐MB‐231 breast tumors).This work highlights a distinct type of titanium‐based nanostructure with a multimodal synergistic integration of sonocatalytic and enzymatic therapies,offering an alternative but highly efficient strategy for fabricating vacancy‐engineered sonocatalytic biomaterials with optimized therapeutic performance in tumor treatment.展开更多
Sonodynamic therapy(SDT)is an innovative cancer therapy modality that harnesses the energy of ultrasound to activate sonosensitizers for producing reactive oxygen species(ROS),culminating in the eradication of tumor c...Sonodynamic therapy(SDT)is an innovative cancer therapy modality that harnesses the energy of ultrasound to activate sonosensitizers for producing reactive oxygen species(ROS),culminating in the eradication of tumor cells.Compared with photodynamic therapy,SDT has the capacity to penetrate deeply into biological tissues,thereby holding significant promise for addressing deeply situated or surgically inaccessible tumors.The effectiveness of SDT is greatly dependent on the characteristics of the sonosensitizers,and unlike inorganic sonosensitizers,organic sonosensitizers offer a more controlled synthesis process and have excellent biocompatibility.This review presents ameticulous undertaking to categorize organic sonosensitizers and elucidate theirmechanisms of action and therapeutic effects in the context of SDT.Design strategies for sonosensitizers are also summarized,and we emphasize the critical role of nanotechnology in tumor localization,imaging,and multimodal synergistic therapy,offering an innovative approach for achieving precise tumor targeting.In addition,the synergistic impact of SDT is delineated when integrated with other oncological modalities,such as photothermal therapy and photodynamic therapy,to enhance therapeutic efficacy.Finally,the review also discusses challenges and future perspectives for the advancement of clinical SDT within the realm of oncology.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)is a new non-invasive treatment method that has received widespread attention due to its deep tissue penetration and high safety.However,the low sonodynamic efficiency of sonosensitizers makes ...Sonodynamic therapy(SDT)is a new non-invasive treatment method that has received widespread attention due to its deep tissue penetration and high safety.However,the low sonodynamic efficiency of sonosensitizers makes SDT poorly effective and limits its bioapplication.Therefore,it is urgent to prepare safe and highly efficient sonosensitizers.Herein,a new kind of sonosensitizer,iron phthalocyanine nanodots(FePc NDs),is fabricated via a facile thermal organic-phase synthesis procedure for enhanced SDT against cancer.Due to the presence of Fe,FePc NDs can also be used as Fenton reagents to efficiently generate hydroxyl radicals(·OH)in the presence of hydrogen peroxide(H_(2)O_(2)).Notably,after modification with polyethylene glycol(PEG),FePc-PEG NDs exhibit remarkable biocompatibility and physiological stability,as well as good tumor accumulation ability.Compared with the control group,in vitro and in vivo experimental results demonstrate obvious cell killing efficiency and significant tumor suppression with the treatment of FePc-PEG NDs under ultrasound(US)irradiation.More importantly,FePc-PEG NDs have good biological safety and do not cause any adverse effects on mice.Our work highlights the use of FePc-PEG NDs as a highly effective and low-toxic sonosensitizer for enhanced SDT.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
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
With the development of engineered nanomaterials and nanomedicines,uti-lization of nanomaterials to generate excessive reactive oxygen species underexogenous ultrasound(US)irradiation for realizing disease therapy,nam...With the development of engineered nanomaterials and nanomedicines,uti-lization of nanomaterials to generate excessive reactive oxygen species underexogenous ultrasound(US)irradiation for realizing disease therapy,namelysonodynamic therapy(SDT),has attracted widespread attention.Comparedwith traditional photodynamic therapy,US shows deeper tissue penetration toreach deep-seated location.However,the development of high-efficiencysonosensitizers remains one of the gravest challenges in current relatedresearch and future clinical application.Latterly,benefiting from the piezo-tronic and piezo-phototronic effects,novel sonosensitizers based on piezo-electric semiconductor(PS)nanomaterials have exhibited inspiring applicationprospects in SDT.In this review,we outline the structures and physico-chemical properties of PS nanomaterials that has potential applications inSDT,and introduce the presumed mechanisms of PS nanomaterials in SDT.Then,the latest research progress of PS nanomaterials as sonosensitizers incancer therapy and antibacterial applications are summarized.Finally,theexisting challenges and future development trends in this field are prospected.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
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
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 Key Research Project of the Educational Department of Liaoning Province,China(No.JYTZD2023139).
文摘Sonodynamic therapy(SDT)is a new non-invasive treatment method,which uses low-intensity ultrasound(US)to activate specific sonosensitizers(SNs)to produce reactive oxygen species(ROS)for therapeutic purposes.However,traditional sonosensitizers have the defects of low generation efficiency of ROS and single treatment mode.Therefore,designing sonosensitizers with high efficiency to generate ROS,high stability,and multimodal therapy is an excellent alternative to achieve effective,safe,and intelligent therapy.Heterojunction nanosonosensitizers(NSNs),as novel type of SNs,combine different materials through heterojunction structures to improve the efficiency of ROS generation.In this review,the classification of heterojunction NSNs,the preparation methods and characterization methods of heterojunction NSNs and the possible mechanisms for enhancing SDT were firstly presented,followed by an in-depth discussion of the application of heterojunction NSNs in the treatment of bacterial infections and tumors,with a special emphasis on synergistic enhancement of therapeutic efficacy of heterojunction SNs in combination with different therapeutic models such as gas therapy,immunotherapy and nanocatalytic therapy.Finally,the challenges and perspectives of such heterojunction SNs-supported SDT were outlined and highlighted to facilitate their clinical translation.
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.
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support from the Natural Science Foundation of Henan,China(Grant No.:202300410446)the National Natural Science Foundation of China(Grant No.:82071950).
文摘Atherosclerosis(AS)is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease,stroke,and peripheral vascular disease.Despite the current treatments,mortality and disability still remain high.Sonodynamic therapy(SDT),a non-invasive and localized methodology,has been developed as a promising new treatment for inhibiting atherosclerotic progression and stabilizing plaques.Promising progress has been made through cell and animal assays,as well as clinical trials.For example,the effect of SDT on apoptosis and autophagy of cells in AS,especially macrophages,and the concept of non-lethal SDT has also been proposed.In this review,we summarize the ultrasonic parameters and known sonosensitizers utilized in SDT for AS;we elaborate on SDT's therapeutic effects and mechanisms in terms of macrophages,T lymphocytes,neovascularization,smooth muscle cells,lipid,extracellular matrix and efferocytosis within plaques;additionally,we discuss the safety of SDT.A comprehensive summary of the confirmed effects of SDT on AS is conducted to establish a framework for future researchers.
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.
文摘Deep-tissue solid cancer treatment has a poor prognosis,resulting in a very low 5-year patient survival rate.The primary challenges facing solid tumor therapies are accessibility,incomplete surgical removal of tumor tissue,the resistance of the hypoxic and heterogeneous tumor microenvironment to chemotherapy and radiation,and suffering caused by off-target toxicities.Here,sonodynamic therapy(SDT)is an evolving therapeutic approach that uses low-intensity ultrasound to target deep-tissue solid tumors.The ability of ultrasound to deliver energy safely and precisely into small deep-tissue(>10 cm)volumes makes SDT more effective than conventional photodynamic therapy.While SDT is currently in phase 1/2 clinical trials for glioblastoma multiforme,its use for other solid cancer treatments,such as breast,pancreatic,liver,and prostate cancer,is still in the preclinical stage,with further investigation required to improve its therapeutic efficacy.This review,therefore,focuses on recent advances in SDT cancer treatments.We describe the interaction between ultrasound and sonosensitizer molecules and the associated energy transfer mechanism to malignant cells,which plays a central role in SDT-mediated cell death.Different sensitizers used in clinical and preclinical trials of various cancer treatments are listed,and the critical ultrasound parameters for SDT are reviewed.We also discuss approaches to improve the efficacies of these sonosensitizers,the role of the 3-dimensional spheroid in vitro investigations,ultrasound-controlled CAR-T cell and SDT-based multimodal therapy,and machine learning for sonosensitizer optimization,which could facilitate clinical translation of SDT.
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 Innovation and Entrepreneurship Training Program for College Students(X2025102911746,X2025102910483).
文摘Natural product(NPT)derived from traditional Chinese medicine has a rich history as an integral part of Chinese healthcare for thousands of years.Recently,the application of NPT in sonodynamic antibacterial therapy(SDAT)has emerged as a promising area of research.This perspective summarizes the recent NPT-based sonosensitizers in SDAT.Currently,common NPT-based sonosensitizers include curcumin,chlorophyll derivatives,hypericin,and berberine.Compared with other sonosensitizers,natural sources of NPT-based sonosensitizers with reactive oxide species production performance under ultrasound conditions,low biotoxicity,and other additional biological activity make them have application prospects in bacterial removal.Finally,the potential benefits and challenges of NPT-based nanosonosensitizers were also discussed.
基金financially supported by the Hunan Provincial Natural Science Foundation(Grants 2024RC3206,2022JJ40375,2021JJ304060,LINC00475,and 2023JJ40552)the Scientific Research Fund of Hunan Provincial Education Department(Grants 22A0287 and 22B0404)the Open Fund of Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates,Guangzhou 510640,China(South China University of Technology)(Grant 2023B1212060003).
文摘Immunogenic cell death(ICD)has been demonstrated as a reliable approach to improve therapeutic effect in cancer treatment by triggering antitumor immunity.However,the trigger of ICD on the basis of chemotherapy and phototherapy meets the obstacles of serious side effect and poor penetration ability,which seriously impedes the therapeutic effect.The development of sonodynamic immunotherapy with the evoking of ICD presents high promise for cancer treatment with high efficacy.Herein,high performance aggregation-induced emission(AIE)sonosensitizer is constructed on the basis of the engineering structure modulation for sonodynamic-augmented immunotherapy.By regulating the intermolecular interaction and pull-push electronic effect,sonosensitizer bearing AIE feature and amplified sono-sensitizing effect is developed.In addition,in vitro observation demonstrated that thiolate-substituted segment incorporation endows the molecules with enhanced cellular uptake efficiency and improved tumor cell eradication ability.More importantly,the developed sonosensitizer could efficiently evoke ICD upon the trigger of ultrasound,which allows for the efficient tumor eradication both at cellular level and in solid tumor.The inhibition of primary tumor and further boost systemic immunity response with the complete elimination toward the distant tumor is achieved.The investigation highlights the promise of utilizing AIE sonosensitizers in sonodynamic immunotherapy to conquer the current limitation of immunotherapy in solid tumor treatment.
基金support from the Shanghai Science and Technology Program(Grant 22ZR1476600)Shanghai Shuguang Program(Grant 21SG39)+1 种基金National Natural Science Foundation of China(Grant 82102085)Basic Research Program of Shanghai Municipal Government(Grant 21JC1406002).
文摘Regulated cell death(RCD)is considered a vital process in cancer therapy,determining treatment outcomes and facilitating the eradication of cancer cells.As an emerging type of RCD,PANoptosis features excellent antineoplastic effects due to its combination of death modes,including pyroptosis,apoptosis,and necroptosis.In this work,anion‐cation vacancies(oxygen/titanium‐vacancy‐rich)ultrathin HTiO nanosheets with outstanding sonocatalytic performance and peroxidase‐mimicking activity are rationally engineered for the disruption of mitochondrial function in tumor cells and the destabilization of redox homeostasis,ultimately inducing tumor PANoptosis.The utilization of external ultrasound energy amplifies the production of toxic reactive oxygen species(ROS).Density functional theory calculations indicate that the oxygen and titanium vacancies generated in HTiO nanosheets enhance the ROS generation efficiency by promoting carrier separation and increasing the adsorption capacity of H_(2)O_(2).The advantages of triggering PANoptosis are substantially evidenced by exceptional antineoplastic efficacy both at the cellular level and on two in vivo separate tumor xenografts(4T1 and MDA‐MB‐231 breast tumors).This work highlights a distinct type of titanium‐based nanostructure with a multimodal synergistic integration of sonocatalytic and enzymatic therapies,offering an alternative but highly efficient strategy for fabricating vacancy‐engineered sonocatalytic biomaterials with optimized therapeutic performance in tumor treatment.
基金supported by the Natural Science Foundation of Shaanxi Province(2023-YBSF-270)the Horizontal Project of the First Affiliated Hospital of Xi’an Jiaotong University(202304174)+1 种基金the Undergraduate Innovation and Entrepreneurship Training Program of Jiangsu Province(202310304155Y)Omer Aras was partially supported by the US National Institutes of Health/National Cancer Institute Cancer Center Support Grant(P30 CA008748).
文摘Sonodynamic therapy(SDT)is an innovative cancer therapy modality that harnesses the energy of ultrasound to activate sonosensitizers for producing reactive oxygen species(ROS),culminating in the eradication of tumor cells.Compared with photodynamic therapy,SDT has the capacity to penetrate deeply into biological tissues,thereby holding significant promise for addressing deeply situated or surgically inaccessible tumors.The effectiveness of SDT is greatly dependent on the characteristics of the sonosensitizers,and unlike inorganic sonosensitizers,organic sonosensitizers offer a more controlled synthesis process and have excellent biocompatibility.This review presents ameticulous undertaking to categorize organic sonosensitizers and elucidate theirmechanisms of action and therapeutic effects in the context of SDT.Design strategies for sonosensitizers are also summarized,and we emphasize the critical role of nanotechnology in tumor localization,imaging,and multimodal synergistic therapy,offering an innovative approach for achieving precise tumor targeting.In addition,the synergistic impact of SDT is delineated when integrated with other oncological modalities,such as photothermal therapy and photodynamic therapy,to enhance therapeutic efficacy.Finally,the review also discusses challenges and future perspectives for the advancement of clinical SDT within the realm of oncology.
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。
文摘Sonodynamic therapy(SDT)is a new non-invasive treatment method that has received widespread attention due to its deep tissue penetration and high safety.However,the low sonodynamic efficiency of sonosensitizers makes SDT poorly effective and limits its bioapplication.Therefore,it is urgent to prepare safe and highly efficient sonosensitizers.Herein,a new kind of sonosensitizer,iron phthalocyanine nanodots(FePc NDs),is fabricated via a facile thermal organic-phase synthesis procedure for enhanced SDT against cancer.Due to the presence of Fe,FePc NDs can also be used as Fenton reagents to efficiently generate hydroxyl radicals(·OH)in the presence of hydrogen peroxide(H_(2)O_(2)).Notably,after modification with polyethylene glycol(PEG),FePc-PEG NDs exhibit remarkable biocompatibility and physiological stability,as well as good tumor accumulation ability.Compared with the control group,in vitro and in vivo experimental results demonstrate obvious cell killing efficiency and significant tumor suppression with the treatment of FePc-PEG NDs under ultrasound(US)irradiation.More importantly,FePc-PEG NDs have good biological safety and do not cause any adverse effects on mice.Our work highlights the use of FePc-PEG NDs as a highly effective and low-toxic sonosensitizer for enhanced SDT.
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Strategic Priority Research Program of the Chinese Academy of Sciences,Grant/Award Number:XDA16021103National Natural Science Foundation of China,Grant/Award Numbers:81471784,82072065+1 种基金National Youth Talent Support ProgramFundamental Research Funds for the Central Universities,Grant/Award Number:E2EG6802X2。
文摘With the development of engineered nanomaterials and nanomedicines,uti-lization of nanomaterials to generate excessive reactive oxygen species underexogenous ultrasound(US)irradiation for realizing disease therapy,namelysonodynamic therapy(SDT),has attracted widespread attention.Comparedwith traditional photodynamic therapy,US shows deeper tissue penetration toreach deep-seated location.However,the development of high-efficiencysonosensitizers remains one of the gravest challenges in current relatedresearch and future clinical application.Latterly,benefiting from the piezo-tronic and piezo-phototronic effects,novel sonosensitizers based on piezo-electric semiconductor(PS)nanomaterials have exhibited inspiring applicationprospects in SDT.In this review,we outline the structures and physico-chemical properties of PS nanomaterials that has potential applications inSDT,and introduce the presumed mechanisms of PS nanomaterials in SDT.Then,the latest research progress of PS nanomaterials as sonosensitizers incancer therapy and antibacterial applications are summarized.Finally,theexisting challenges and future development trends in this field are prospected.
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.
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.
