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
AIMTo evaluate the efficacy and safety of a combined treatment for myopic choroidal neovascularization (CNV) using photodynamic therapy (PDT) and intravitreal bevacizumab and to compare it with intravitreal bevacizuma...AIMTo evaluate the efficacy and safety of a combined treatment for myopic choroidal neovascularization (CNV) using photodynamic therapy (PDT) and intravitreal bevacizumab and to compare it with intravitreal bevacizumab monotherapy.展开更多
AIMTo compare the efficacy of intravitreal ranibizumab (IVR) alone or in combination with photodynamic therapy (PDT) vs PDT in patients with symptomatic polypoidal choroidal vasculopathy (PCV).METHODSA systematic sear...AIMTo compare the efficacy of intravitreal ranibizumab (IVR) alone or in combination with photodynamic therapy (PDT) vs PDT in patients with symptomatic polypoidal choroidal vasculopathy (PCV).METHODSA systematic search of a wide range of databases (including PubMed, EMBASE, Cochrane Library and Web of Science) was searched to identify relevant studies. Both randomized controlled trials (RCTs) and non-RCT studies were included. Methodological quality of included literatures was evaluated according to the Newcastle-Ottawa Scale. RevMan 5.2.7 software was used to do the Meta-analysis.RESULTSThree RCTs and 6 retrospective studies were included. The results showed that PDT monotherapy had a significantly higher proportion in patients who achieved complete regression of polyps than IVR monotherapy at months 3, 6, and 12 (All P≤0.01), respectively. However, IVR had a tendency to be more effective in improving vision on the basis of RCTs. The proportion of patients who gained complete regression of polyps revealed that there was no significant difference between the combination treatment and PDT monotherapy. The mean change of best-corrected visual acuity (BCVA) from baseline showed that the combination treatment had significant superiority in improving vision vs PDT monotherapy at months 3, 6 and 24 (All P<0.05), respectively. In the mean time, this comparison result was also significant at month 12 (P<0.01) after removal of a heterogeneous study.CONCLUSIONIVR has non-inferiority compare with PDT either in stabilizing or in improving vision, although it can hardly promote the regression of polyps. The combination treatment of PDT and IVR can exert a synergistic effect on regressing polyps and on maintaining or improving visual acuity. Thus, it can be the first-line therapy for PCV.展开更多
Indocyanine green(ICG) is capable of inducing a photothermal effect and the production of cytotoxic reactive oxygen species for cancer therapy. However, the major challenge in applying ICG molecules for antitumor ther...Indocyanine green(ICG) is capable of inducing a photothermal effect and the production of cytotoxic reactive oxygen species for cancer therapy. However, the major challenge in applying ICG molecules for antitumor therapy is associated with their instability in aqueous conditions and rapid clearance from blood circulation,which causes insufficient bioavailability at the tumor site.Herein, we conjugated ICG molecules with Prussian blue nanoparticles enclosing a Fe_3O_4 nanocore, which was facilitated by cationic polyethyleneimine via electrostatic adsorption. The nanocarrier-loaded ICG formed stable aggregates that enhanced cellular uptake and prevented fluorescence quenching. Moreover, the strong superparamagnetism of the Fe_3O_4 core in the obtained nanocomposites further improved cellular internalization of the drugs guided by a localized magnetic field. The therapeutic efficacy of this nanoplatform was evaluated using tumor models established in nude mice, which demonstrated remarkable tumor ablation in vivo due to strong photothermal/photodynamic effects. This study provides promising evidence that this multifunctional nanoagent might function as an efficient mediator for combining photothermal and photodynamic cancer therapy.展开更多
Photodynamic therapy is a minimally invasive and clinically approved procedure for eliminating selected malignant cells with specific light activation of a photosensitizer agent. Whereas interstitial and intra-operati...Photodynamic therapy is a minimally invasive and clinically approved procedure for eliminating selected malignant cells with specific light activation of a photosensitizer agent. Whereas interstitial and intra-operative approaches have been investigated for the ablation of a broad range of superficial or bulky solid tumors such as breast cancer, the majority of approved photodynamic therapy protocols are for the treatment of superficial lesions of skin and luminal organs. This review article will discuss recent progress in research focused mainly on assessing the efficacies of various photosensitizers used in photodynamic therapy, as well as the combinatory strategies of various therapeutic modalities for improving treatments of parenchymal and/or stromal tissues of breast cancer solid tumors. Cytotoxic agents are used in cancer treatments for their effect on rapidly proliferating cancer cells. However, such therapeutics often lack specificity, which can lead to toxicity and undesirable side effects. Many approaches are designed to targettumors. Selective therapies can be established by focusing on distinctive intracellular(receptors, apoptotic pathways, multidrug resistance system, nitric oxidemediated stress) and environmental(glucose, pH) differences between tumor and healthy tissue. A rational design of effective combination regimens for breast cancer treatment involves a better understanding of the mechanisms and molecular interactions of cytotoxic agents that underlie drug resistance and sensitivity.展开更多
Drug resistance is considered the most important reason for the clinical failure of cancer chemotherapy.Circumventing drug resistance and improving the efficacy of anticancer agents remains a major challenge.Over the ...Drug resistance is considered the most important reason for the clinical failure of cancer chemotherapy.Circumventing drug resistance and improving the efficacy of anticancer agents remains a major challenge.Over the past several decades,photodynamic therapy(PDT)and sonodynamic therapy(SDT)have attracted substantial attention for their efficacy in cancer treatment,and have been combined with chemotherapy to overcome drug resistance.However,simultaneously delivering sensitizers and chemotherapy drugs to same tumor cell remains challenging,thus greatly limiting this combinational therapy.The rapid development of nanotechnology provides a new approach to solve this problem.Nano-based drug delivery systems can not only improve the targeted delivery of agents but also co-deliver multiple drug components in single nanoparticles to achieve optimal synergistic effects.In this review,we briefly summarize the mechanisms of drug resistance,discuss the advantages and disadvantages of PDT and SDT in reversing drug resistance,and describe state-of-the-art research using nano-mediated PDT and SDT to solve these refractory problems.This review also highlights the clinical translational potential for this combinational therapy.展开更多
Patients with pancreatic cancer(PCa)have a poor prognosis apart from the few suitable for surgery.Photodynamic therapy(PDT)is a minimally invasive treatment modality whose efficacy and safety in treating unresectable ...Patients with pancreatic cancer(PCa)have a poor prognosis apart from the few suitable for surgery.Photodynamic therapy(PDT)is a minimally invasive treatment modality whose efficacy and safety in treating unresectable localized PCa have been corroborated in clinic.Yet,it suffers from certain limitations during clinical exploitation,including insufficient photosensitizers(PSs)delivery,tumor-oxygenation dependency,and treatment escape of aggressive tumors.To overcome these obstacles,an increasing number of researchers are currently on a quest to develop photosensitizer nanoparticles(NPs)by the use of a variety of nanocarrier systems to improve cellular uptake and biodistribution of photosensitizers.Encapsulation of PSs with NPs endows them significantly higher accumulation within PCa tumors due to the increased solubility and stability in blood circulation.A number of approaches have been explored to produce NPs co-delivering multi-agents affording PDT-based synergistic therapies for improved response rates and durability of response after treatment.This review provides an overview of available data regarding the design,methodology,and oncological outcome of the innovative NPs-based PDT of PCa.展开更多
Photodynamic therapy(PDT)is highly effective in treating tumors located near body surface,offering strong tumor suppression and low damage to normal tissue nearby.PDT is also effective for treating a number of other c...Photodynamic therapy(PDT)is highly effective in treating tumors located near body surface,offering strong tumor suppression and low damage to normal tissue nearby.PDT is also effective for treating a number of other conditions.PDT not only provide a precise and selective method for the treatment of various diseases by itself,it can also be used in combination with other traditional therapies.Because PDT uses light as the unique targeting mechanism,it has simpler and more direct targeting capability than traditional therapies.The core material of a PDT system is the photosensitizer which converts light energy to therapeutic factors/substances.Different photosensitizers have their distinct characteristics,leading to different advantages and disadvantages.These could be enhanced or compensated by using proper PDT system.Therefore,the selected type of photosensitizer would heavily influence the overall design of a PDT system.In this article,we evaluated major types of inorganic and organic PDT photosensitizers,and discussed future research directions in the field.展开更多
Cancer remains one of the diseases with the highest incidence and mortality globally.Conventional treatment modalities have demonstrated threatening drawbacks including invasiveness,noncontrollability,and development ...Cancer remains one of the diseases with the highest incidence and mortality globally.Conventional treatment modalities have demonstrated threatening drawbacks including invasiveness,noncontrollability,and development of resistance for some,including chemotherapy,radiation,and surgery.Sono-photodynamic combinatorial therapy(SPDT)has been developed as an alternative treatment modality which offers a non-invasive and controllable therapeutic approach.SPDT combines the mechanism of action of sonodynamic therapy(SDT),which uses ultrasound,and photodynamic therapy(PDT),which uses light,to activate a sensitizer and initiate cancer eradication.The use of phthalocyanines(Pcs)as sensitizers for SPDT is gaining interest owing to their ability to induce intracellular oxidative stress and initiate toxicity under SDT and PDT.This review discusses some of the structural prerequisites of Pcs which may influence their overall SPDT activities in cancer therapy.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
The therapeutic efficiency of sonodynamic therapy(SDT)mainly depends on the presence of oxygen(O_(2))to generate harmful reactive oxygen species(ROS);thus,the hypoxic tumor microenvironment significantly limits the ef...The therapeutic efficiency of sonodynamic therapy(SDT)mainly depends on the presence of oxygen(O_(2))to generate harmful reactive oxygen species(ROS);thus,the hypoxic tumor microenvironment significantly limits the efficacy of SDT.Therefore,the development of oxygen-independent free radical generators and associated combination therapy tactics can be a promising field to facilitate the anticancer capability of SDT.In this study,a biomimetic drug delivery system(C-TiO_(2)/AIPH@PM)composed of an alkyl-radical generator(2,2′-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride,AIPH)-loaded C-TiO_(2) hollow nanoshells(HNSs)as the inner cores,and a platelet membrane(PM)as the outer shells is successfully prepared for synergistic SDT and oxygen-independent alkyl-radical therapy.The PM encapsulation can significantly prolong the blood circulation time of CTiO_(2)/AIPH@PM compared with C-TiO_(2)/AIPH while enabling C-TiO_(2)/AIPH@PM to achieve tumor targeting.C-TiO_(2)/AIPH@PM can efficiently produce ROS and alkyl radicals,which can achieve a more thorough tumor eradication regardless of the normoxic or hypoxic conditions.Furthermore,the generation of these radicals improves the efficiency of SDT.In addition,nitrogen(N_(2))produced due to the decomposition of AIPH enhances the acoustic cavitation effect and lowers the cavitation threshold,thereby enhancing the penetration of CTiO_(2)/AIPH@PM at the tumor sites.Both in vitro and in vivo experiments demonstrate that CTiO_(2)/AIPH@PM possesses good biosafety,ultrasound imaging performance,and excellent anticancer efficacy.This study provides a new strategy to achieve oxygen-independent free radical production and enhance therapeutic efficacy by combining SDT and free radical therapy.展开更多
Rapid evolution and propagation of multidrug resistance among bacterial pathogens are outpacing the development of new antibiotics,but antimicrobial photodynamic therapy(aPDT)provides an excellent alternative.This tre...Rapid evolution and propagation of multidrug resistance among bacterial pathogens are outpacing the development of new antibiotics,but antimicrobial photodynamic therapy(aPDT)provides an excellent alternative.This treatment depends on the interaction between light and photoactivated sensitizer to generate reactive oxygen species(ROS),which are highly cytotoxic to induce apoptosis in virtually all microorganisms without resistance concern.When replacing light with low-frequency ultrasonic wave to activate sensitizer,a novel ultrasounddriven treatment emerges as antimicrobial sonodynamic therapy(aSDT).Recent advances in aPDT and aSDT reveal golden opportunities for the management of multidrug resistant bacterial infections,especially in the theranostic application where imaging diagnosis can be accomplished facilely with the inherent optical characteristics of sensitizers,and the generated ROS by aPDT/SDT cause broad-spectrum oxidative damage for sterilization.In this review,we systemically outline the mechanisms,targets,and current progress of aPDT/SDT for bacterial theranostic application.Furthermore,potential limitations and future perspectives are also highlighted.展开更多
The immune system has the function of immune surveillance to resist the occurrence and development of tumors,and is essential for inhibition of tumor metastasis.Nevertheless,tumor cells can still suppress immune respo...The immune system has the function of immune surveillance to resist the occurrence and development of tumors,and is essential for inhibition of tumor metastasis.Nevertheless,tumor cells can still suppress immune responses through multiple mechanisms to escape recognition and elimination.Photodynamic and sonodynamic therapy involve systemic or local use of sensitizers followed by light or ultrasound treatment of the affected area,leading to tumor cell death by various mechanisms.The capability of the immune system is essentially affected by photodynamic and sonodynamic therapy.To understand the tumor therapeutic mechanisms of photodynamic and sonodynamic therapy and to explore the use of these modalities for improvement of the antitumor immune effect,extensive preclinical and clinical studies have been carried out.Besides direct killing of tumors,photodynamic and sonodynamic therapy also cause inflammatory reactions,achieve antitumor immune responses,and potentially prevent tumor recurrence,thereby treating both primary and metastatic tumors.In this review,we summarize the antitumor immune responses induced by photodynamic and sonodynamic therapy,describe the processes of the antitumor immune responses in detail,and discuss the clinical applications of the resulting antitumor immunity.展开更多
Nanoscale metal organic frameworks (NMOFs) with porous structure and inherent biodegradability are attractive nanomedicine platforms.In addition to conventional particulate NMOFs,two-dimensional (2D) NMOFs are emergin...Nanoscale metal organic frameworks (NMOFs) with porous structure and inherent biodegradability are attractive nanomedicine platforms.In addition to conventional particulate NMOFs,two-dimensional (2D) NMOFs are emerging as a unique type of NMOFs which however have been relatively less explored for nanomedicine applications.Herein,2D NMOFs composed of Zn2+ and tetrakis(4-carboxyphenyl) porphyrin (TCPP) are fabricated and functionalized with polyethylene glycol (PEG).Compared to their particulate counterpart,such 2D NMOFs show greatly increased drug loading capacity and enhanced light-triggered singlet oxygen production,promising for chemotherapy and photodynamic therapy (PDT),respectively.Utilizing the porphyrin structure of TCPP,our 2D NMOFs could be labeled with a diagnostic radioisotope,99mTc,for single photon emission computer tomography (SPECT) imaging,which reveals efficient tumor homing of those 2D NMOFs upon intravenous injection.While offering a remarkable synergistic in vivo antitumor effect for the combined chemo-PDT,such 2D NMOFs show efficient biodegradation and rapid renal clearance.Our work presents the great promise of 2D NMOFs for nanomedicine applications.展开更多
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.
文摘AIMTo evaluate the efficacy and safety of a combined treatment for myopic choroidal neovascularization (CNV) using photodynamic therapy (PDT) and intravitreal bevacizumab and to compare it with intravitreal bevacizumab monotherapy.
基金Supported by the National Natural Science Foundation of China(No.81373826,No.81100658)Development Project of Science and Technology of Traditional Chinese Medicine of Shandong Province(No.2013ZDZK-083)Development Project of Medicine and Health Science Technology of Shandong Province(No.2013WS0251)
文摘AIMTo compare the efficacy of intravitreal ranibizumab (IVR) alone or in combination with photodynamic therapy (PDT) vs PDT in patients with symptomatic polypoidal choroidal vasculopathy (PCV).METHODSA systematic search of a wide range of databases (including PubMed, EMBASE, Cochrane Library and Web of Science) was searched to identify relevant studies. Both randomized controlled trials (RCTs) and non-RCT studies were included. Methodological quality of included literatures was evaluated according to the Newcastle-Ottawa Scale. RevMan 5.2.7 software was used to do the Meta-analysis.RESULTSThree RCTs and 6 retrospective studies were included. The results showed that PDT monotherapy had a significantly higher proportion in patients who achieved complete regression of polyps than IVR monotherapy at months 3, 6, and 12 (All P≤0.01), respectively. However, IVR had a tendency to be more effective in improving vision on the basis of RCTs. The proportion of patients who gained complete regression of polyps revealed that there was no significant difference between the combination treatment and PDT monotherapy. The mean change of best-corrected visual acuity (BCVA) from baseline showed that the combination treatment had significant superiority in improving vision vs PDT monotherapy at months 3, 6 and 24 (All P<0.05), respectively. In the mean time, this comparison result was also significant at month 12 (P<0.01) after removal of a heterogeneous study.CONCLUSIONIVR has non-inferiority compare with PDT either in stabilizing or in improving vision, although it can hardly promote the regression of polyps. The combination treatment of PDT and IVR can exert a synergistic effect on regressing polyps and on maintaining or improving visual acuity. Thus, it can be the first-line therapy for PCV.
基金financial support from Fundamental Research Funds for Central Universities (XDJK2016A010 and XDJK2017C001)National Natural Science Foundation of China (51703186 and 31671037)Southwest University (SWU116032 and SWU115059)
文摘Indocyanine green(ICG) is capable of inducing a photothermal effect and the production of cytotoxic reactive oxygen species for cancer therapy. However, the major challenge in applying ICG molecules for antitumor therapy is associated with their instability in aqueous conditions and rapid clearance from blood circulation,which causes insufficient bioavailability at the tumor site.Herein, we conjugated ICG molecules with Prussian blue nanoparticles enclosing a Fe_3O_4 nanocore, which was facilitated by cationic polyethyleneimine via electrostatic adsorption. The nanocarrier-loaded ICG formed stable aggregates that enhanced cellular uptake and prevented fluorescence quenching. Moreover, the strong superparamagnetism of the Fe_3O_4 core in the obtained nanocomposites further improved cellular internalization of the drugs guided by a localized magnetic field. The therapeutic efficacy of this nanoplatform was evaluated using tumor models established in nude mice, which demonstrated remarkable tumor ablation in vivo due to strong photothermal/photodynamic effects. This study provides promising evidence that this multifunctional nanoagent might function as an efficient mediator for combining photothermal and photodynamic cancer therapy.
基金Supported by funds provided by CONICET(PIP 112-201101-00453),SECyT,FONCyT(PICT 2011-1328),and MinCyT Córdoba(PID 2010)
文摘Photodynamic therapy is a minimally invasive and clinically approved procedure for eliminating selected malignant cells with specific light activation of a photosensitizer agent. Whereas interstitial and intra-operative approaches have been investigated for the ablation of a broad range of superficial or bulky solid tumors such as breast cancer, the majority of approved photodynamic therapy protocols are for the treatment of superficial lesions of skin and luminal organs. This review article will discuss recent progress in research focused mainly on assessing the efficacies of various photosensitizers used in photodynamic therapy, as well as the combinatory strategies of various therapeutic modalities for improving treatments of parenchymal and/or stromal tissues of breast cancer solid tumors. Cytotoxic agents are used in cancer treatments for their effect on rapidly proliferating cancer cells. However, such therapeutics often lack specificity, which can lead to toxicity and undesirable side effects. Many approaches are designed to targettumors. Selective therapies can be established by focusing on distinctive intracellular(receptors, apoptotic pathways, multidrug resistance system, nitric oxidemediated stress) and environmental(glucose, pH) differences between tumor and healthy tissue. A rational design of effective combination regimens for breast cancer treatment involves a better understanding of the mechanisms and molecular interactions of cytotoxic agents that underlie drug resistance and sensitivity.
基金supported by grants from the National Key Research and Development Program of China(Grant No.2016YFA0201400)State Key Program of National Natural Science of China(Grant No.81930047)+4 种基金Projects of International Cooperation and Exchanges NSFC-PSF(Grant No.31961143003)National Project for Research and Development of Major Scientific Instruments(Grant No.81727803)Beijing Natural Science Foundation,Haidian,Original Innovation Joint Fund(Grant No.17 L20170)Foundation for Innovative Research Groups of the National Natural Science Foundation of China(Grant Nos.81421004 and 52003161)Shenzhen Science and Technology Project(Grant No.JCYJ20180507183842516)。
文摘Drug resistance is considered the most important reason for the clinical failure of cancer chemotherapy.Circumventing drug resistance and improving the efficacy of anticancer agents remains a major challenge.Over the past several decades,photodynamic therapy(PDT)and sonodynamic therapy(SDT)have attracted substantial attention for their efficacy in cancer treatment,and have been combined with chemotherapy to overcome drug resistance.However,simultaneously delivering sensitizers and chemotherapy drugs to same tumor cell remains challenging,thus greatly limiting this combinational therapy.The rapid development of nanotechnology provides a new approach to solve this problem.Nano-based drug delivery systems can not only improve the targeted delivery of agents but also co-deliver multiple drug components in single nanoparticles to achieve optimal synergistic effects.In this review,we briefly summarize the mechanisms of drug resistance,discuss the advantages and disadvantages of PDT and SDT in reversing drug resistance,and describe state-of-the-art research using nano-mediated PDT and SDT to solve these refractory problems.This review also highlights the clinical translational potential for this combinational therapy.
基金financially supported by Beijing Natural Science Foundation,Haidian,original innovation joint fund(No.17L20170)National Key Research and Development Program of China(No.2016YFA0201400)+3 种基金State Key Program of National Natural Science of China(No.81930047)Projects of International Cooperation and Exchanges NSFC-PSF(No.31961143003)National Project for Research and Development of Major Scientific Instruments(No.81727803)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(No.81421004).
文摘Patients with pancreatic cancer(PCa)have a poor prognosis apart from the few suitable for surgery.Photodynamic therapy(PDT)is a minimally invasive treatment modality whose efficacy and safety in treating unresectable localized PCa have been corroborated in clinic.Yet,it suffers from certain limitations during clinical exploitation,including insufficient photosensitizers(PSs)delivery,tumor-oxygenation dependency,and treatment escape of aggressive tumors.To overcome these obstacles,an increasing number of researchers are currently on a quest to develop photosensitizer nanoparticles(NPs)by the use of a variety of nanocarrier systems to improve cellular uptake and biodistribution of photosensitizers.Encapsulation of PSs with NPs endows them significantly higher accumulation within PCa tumors due to the increased solubility and stability in blood circulation.A number of approaches have been explored to produce NPs co-delivering multi-agents affording PDT-based synergistic therapies for improved response rates and durability of response after treatment.This review provides an overview of available data regarding the design,methodology,and oncological outcome of the innovative NPs-based PDT of PCa.
基金support received from Sichuan Science and Technology Program(2019JDJQ0028)。
文摘Photodynamic therapy(PDT)is highly effective in treating tumors located near body surface,offering strong tumor suppression and low damage to normal tissue nearby.PDT is also effective for treating a number of other conditions.PDT not only provide a precise and selective method for the treatment of various diseases by itself,it can also be used in combination with other traditional therapies.Because PDT uses light as the unique targeting mechanism,it has simpler and more direct targeting capability than traditional therapies.The core material of a PDT system is the photosensitizer which converts light energy to therapeutic factors/substances.Different photosensitizers have their distinct characteristics,leading to different advantages and disadvantages.These could be enhanced or compensated by using proper PDT system.Therefore,the selected type of photosensitizer would heavily influence the overall design of a PDT system.In this article,we evaluated major types of inorganic and organic PDT photosensitizers,and discussed future research directions in the field.
基金supported by the National Research Foundation of South Africabased on the research supported by the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa(Grant No.98337)+2 种基金the University of Johannesburgthe National Laser Centrethe National Research Foundation-South African Research Chairs Initiative(NRF-SARChI)for their financial grant support。
文摘Cancer remains one of the diseases with the highest incidence and mortality globally.Conventional treatment modalities have demonstrated threatening drawbacks including invasiveness,noncontrollability,and development of resistance for some,including chemotherapy,radiation,and surgery.Sono-photodynamic combinatorial therapy(SPDT)has been developed as an alternative treatment modality which offers a non-invasive and controllable therapeutic approach.SPDT combines the mechanism of action of sonodynamic therapy(SDT),which uses ultrasound,and photodynamic therapy(PDT),which uses light,to activate a sensitizer and initiate cancer eradication.The use of phthalocyanines(Pcs)as sensitizers for SPDT is gaining interest owing to their ability to induce intracellular oxidative stress and initiate toxicity under SDT and PDT.This review discusses some of the structural prerequisites of Pcs which may influence their overall SPDT activities in cancer therapy.
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This work was supported by the Research fund of Anhui Institute of Translation Medicine(No.2021zhyx-C49)the Foundation of Anhui Medical University(No.2021xkj030)+2 种基金the Anhui Provincial Natural Science Foundation(No.2208085QC81)the Basic and Clinical Cooperative Research and Promotion Program of Anhui Medical University(No.2021xkjT028)Grants for Scientific Research of BSKY from Anhui Medical University(No.1406012201).
文摘The therapeutic efficiency of sonodynamic therapy(SDT)mainly depends on the presence of oxygen(O_(2))to generate harmful reactive oxygen species(ROS);thus,the hypoxic tumor microenvironment significantly limits the efficacy of SDT.Therefore,the development of oxygen-independent free radical generators and associated combination therapy tactics can be a promising field to facilitate the anticancer capability of SDT.In this study,a biomimetic drug delivery system(C-TiO_(2)/AIPH@PM)composed of an alkyl-radical generator(2,2′-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride,AIPH)-loaded C-TiO_(2) hollow nanoshells(HNSs)as the inner cores,and a platelet membrane(PM)as the outer shells is successfully prepared for synergistic SDT and oxygen-independent alkyl-radical therapy.The PM encapsulation can significantly prolong the blood circulation time of CTiO_(2)/AIPH@PM compared with C-TiO_(2)/AIPH while enabling C-TiO_(2)/AIPH@PM to achieve tumor targeting.C-TiO_(2)/AIPH@PM can efficiently produce ROS and alkyl radicals,which can achieve a more thorough tumor eradication regardless of the normoxic or hypoxic conditions.Furthermore,the generation of these radicals improves the efficiency of SDT.In addition,nitrogen(N_(2))produced due to the decomposition of AIPH enhances the acoustic cavitation effect and lowers the cavitation threshold,thereby enhancing the penetration of CTiO_(2)/AIPH@PM at the tumor sites.Both in vitro and in vivo experiments demonstrate that CTiO_(2)/AIPH@PM possesses good biosafety,ultrasound imaging performance,and excellent anticancer efficacy.This study provides a new strategy to achieve oxygen-independent free radical production and enhance therapeutic efficacy by combining SDT and free radical therapy.
基金supported by the National Key Research and Development Program of China(2017YFA0205201 and 2016YFC0106900)the National Natural Science Foundation of China(81925019,81422023,81701752,81901808,and U1705281)+2 种基金the Fundamental Research Funds for the Central Universities(20720200019 and 20720190088)the Program for New Century Excellent Talents in University,China(No.NCET-13-0502)the China Postdoctoral Science Foundation(2019M662545)。
文摘Rapid evolution and propagation of multidrug resistance among bacterial pathogens are outpacing the development of new antibiotics,but antimicrobial photodynamic therapy(aPDT)provides an excellent alternative.This treatment depends on the interaction between light and photoactivated sensitizer to generate reactive oxygen species(ROS),which are highly cytotoxic to induce apoptosis in virtually all microorganisms without resistance concern.When replacing light with low-frequency ultrasonic wave to activate sensitizer,a novel ultrasounddriven treatment emerges as antimicrobial sonodynamic therapy(aSDT).Recent advances in aPDT and aSDT reveal golden opportunities for the management of multidrug resistant bacterial infections,especially in the theranostic application where imaging diagnosis can be accomplished facilely with the inherent optical characteristics of sensitizers,and the generated ROS by aPDT/SDT cause broad-spectrum oxidative damage for sterilization.In this review,we systemically outline the mechanisms,targets,and current progress of aPDT/SDT for bacterial theranostic application.Furthermore,potential limitations and future perspectives are also highlighted.
基金the National Project for Research and Development of Major Scientific Instruments(No.81727803)State Key Program of National Natural Science of China(No.81930047)+3 种基金National Key Research and Development Program of China(No.2016YFA0201400)Projects of International Cooperation and Exchanges NSFC(National Natural Science Foundation of China)-PSF(Pakistan Science Foundation)(No.31961143003)Beijing Natural Science Foundation,Haidian,Original Innovation Joint Fund(No.17L20170)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(No.81421004).
文摘The immune system has the function of immune surveillance to resist the occurrence and development of tumors,and is essential for inhibition of tumor metastasis.Nevertheless,tumor cells can still suppress immune responses through multiple mechanisms to escape recognition and elimination.Photodynamic and sonodynamic therapy involve systemic or local use of sensitizers followed by light or ultrasound treatment of the affected area,leading to tumor cell death by various mechanisms.The capability of the immune system is essentially affected by photodynamic and sonodynamic therapy.To understand the tumor therapeutic mechanisms of photodynamic and sonodynamic therapy and to explore the use of these modalities for improvement of the antitumor immune effect,extensive preclinical and clinical studies have been carried out.Besides direct killing of tumors,photodynamic and sonodynamic therapy also cause inflammatory reactions,achieve antitumor immune responses,and potentially prevent tumor recurrence,thereby treating both primary and metastatic tumors.In this review,we summarize the antitumor immune responses induced by photodynamic and sonodynamic therapy,describe the processes of the antitumor immune responses in detail,and discuss the clinical applications of the resulting antitumor immunity.
基金the National Research Programs from Ministry of Science and Technology (MOST) of China (No.2016YFA0201200)the National Natural Science Foundation of China (Nos.51525203 and 51761145041)+1 种基金Collaborative Innovation Center of Suzhou Nano Science and Technologya Project Funded by the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions.
文摘Nanoscale metal organic frameworks (NMOFs) with porous structure and inherent biodegradability are attractive nanomedicine platforms.In addition to conventional particulate NMOFs,two-dimensional (2D) NMOFs are emerging as a unique type of NMOFs which however have been relatively less explored for nanomedicine applications.Herein,2D NMOFs composed of Zn2+ and tetrakis(4-carboxyphenyl) porphyrin (TCPP) are fabricated and functionalized with polyethylene glycol (PEG).Compared to their particulate counterpart,such 2D NMOFs show greatly increased drug loading capacity and enhanced light-triggered singlet oxygen production,promising for chemotherapy and photodynamic therapy (PDT),respectively.Utilizing the porphyrin structure of TCPP,our 2D NMOFs could be labeled with a diagnostic radioisotope,99mTc,for single photon emission computer tomography (SPECT) imaging,which reveals efficient tumor homing of those 2D NMOFs upon intravenous injection.While offering a remarkable synergistic in vivo antitumor effect for the combined chemo-PDT,such 2D NMOFs show efficient biodegradation and rapid renal clearance.Our work presents the great promise of 2D NMOFs for nanomedicine applications.