BACKGROUND AND IMPORTANCE Bacterial infections remain a significant public health threat.While antibiotics have mitigated their impact,overuse and misuse have driven the emergence of drug-resistant bacteria,compromisi...BACKGROUND AND IMPORTANCE Bacterial infections remain a significant public health threat.While antibiotics have mitigated their impact,overuse and misuse have driven the emergence of drug-resistant bacteria,compromising treatment outcomes.Additionally,bacterial biofilms have further diminished the effectiveness of current antibiotics,underscoring the urgent need for new antibacterial therapies.Recent advancements in antibacterial nanoagents,show promise due to their unique physical and chemical properties.These nanoagents have been approved by the US Food and Drug Administration.展开更多
Phototherapy showed almost a lack of drug resistance and,depending on the therapeutic effects of non-invasive light-stimulating photosensors.The side effects of phototherapy were greatly reduced compared to their trad...Phototherapy showed almost a lack of drug resistance and,depending on the therapeutic effects of non-invasive light-stimulating photosensors.The side effects of phototherapy were greatly reduced compared to their traditional equivalents.Phototheranostic nanoagents had new properties in drug delivery,biocompatibility,targeting and response,in which traditional phototheranostic drugs can not possess.Recently,a large number of relevant studies have demonstrated that photodynamic therapy(PDT)in combination with other agents and image-guided multifunctional photothermal therapy(PTT)were well suited for the treatment of oral cancer.Through the design of the nanoagents,researchers have discovered various applications for phototherapy,such as targeted release of co-packaged drugs,multifunctional imaging for diagnosis and treatment combination,accurate targeting caused by nanocarriers,and synergistic chemotherapy with phototherapy.In this paper,we first reviewed the research related to phototheranostic nanoagents for image-guided treatment of oral cancer.We tried to introduce the design concept and the treatment effect by three parts of components of phototheranostic nanoagents,categories of phototheranostic nanoagents and application of phototheranostic nanoagents.It also provided a reference for nanomaterial development and clinical applications in research of oral cancer treatment.展开更多
Near-infrared(NIR)absorbing materials hold great potential in biomedical applications,such as fluorescence imaging(FLI),photoacoustic imaging(PAI),photodynamic therapy(PDT),and photothermal therapy(PTT).Generally,thes...Near-infrared(NIR)absorbing materials hold great potential in biomedical applications,such as fluorescence imaging(FLI),photoacoustic imaging(PAI),photodynamic therapy(PDT),and photothermal therapy(PTT).Generally,these materials can be classified into two main categories based on their absorbing wavelengths:the first NIR(NIR-I)(~650–950 nm)absorbing materials and the second NIR(NIR-Ⅱ)(~1000–1700 nm)absorbing materials.Due to the reduced absorption and scattering of NIR-Ⅱlight in tissue compared to NIR-Ⅰlight,NIR-Ⅱabsorbing materials enable imaging and therapy with improved contrast and deepened penetration,which is in favor of practical applications.Various inorganic materials have been developed for NIR-Ⅱphototheranostics in recent years.However,the non-biodegradability and potential toxicity of these materials hinder their further clinical trans-lation.Biocompatible organic materials with potential biodegradability as well as tailored optical property are thus more desired.In this review,we sum-marize the recent advances of NIR-Ⅱabsorbing organic nanoagents(ONAs)based on small molecules(SMs)and conjugated polymers(CPs)for PAI and PTT and show our perspectives on future challenges and development of these materials.展开更多
The integration of photothermal therapy(PTT)with gene therapy(GT)in a single nanoscale platform demonstrates great potential in cancer therapy.Porous iron oxide nanoagents(PIONs)are widely used as magnetic nanoagents ...The integration of photothermal therapy(PTT)with gene therapy(GT)in a single nanoscale platform demonstrates great potential in cancer therapy.Porous iron oxide nanoagents(PIONs)are widely used as magnetic nanoagents in the drug delivery field and also serve as a photothermal nanoagent for photothermal therapy.However,the therapeutic efficacy of PIONs-mediated GT has not been studied.The long noncoding RNA(lncRNA)CRYBG3(LNC CRYBG3),a lncRNA induced by heavy ion irradiation in lung cancer cells,has been reported to directly bind to globular actin(G-actin)and cause degradation of cytoskeleton and blocking of cytokinesis,thus indicating its potential for use in GT by simulating the effect of heavy ion irradiation and functioning as an antitumor drug.In the present study,we investigated the possibility of combining PIONs-mediated PTT and LNC CRYBG3-mediated GT to destroy non-small cell lung cancer(NSCLC)cells both in vitro and in vivo.The combination therapy showed a high cancer cell killing efficacy,and the cure rate was better than that achieved using PTT or GT alone.Moreover,as a type of magnetic nanoagent,PIONs can be used for magnetic resonance imaging(MRI)and photoacoustic imaging(PAI)both in vitro and in vivo.These findings indicate that the new combination therapy has high potential for cancer treatment.展开更多
Affibody molecules are small nonimmunoglobulin affinity proteins,which can precisely target to some cancer cells with specific overexpressed molecular signatures.However,the relatively short in vivo half-life of them ...Affibody molecules are small nonimmunoglobulin affinity proteins,which can precisely target to some cancer cells with specific overexpressed molecular signatures.However,the relatively short in vivo half-life of them seriously limited their application in drug targeted delivery for cancer therapy.Here an amphiphilic affibody-drug conjugate is self-assembled into nanomicelles to prolong circulation time for targeted cancer therapy.As an example of the concept,the nanoagent was prepared through molecular self-assembly of the amphiphilic conjugate of Z_(HHR2:342)-Cys with auristatin E derivate,where the affibody used is capable of binding to the human epidermal growth factor receptor 2(HER2).Such a nanodrug not only increased the blood circulation time,but also enhanced the tumor targeting capacity(abundant affibody arms on the nanoagent surface) and the drug accumulation in tumor.As a result,this affibody-based nanoagent showed excellent antitumor activity in vivo to HER2-positive ovary and breast tumor models,which nearly eradicated both small solid tumors(about 100 mm^(3)) and large established tumors(exceed 500 mm^(3)).The relative tumor proliferation inhibition ratio reaches 99.8% for both models.展开更多
Malignant tumors,with the characteristics of easy metastasis and recurrence,are a serious threat to health of mankind.It is urgent to develop promising clinical cancer targeted agents with combination of rapid diagnos...Malignant tumors,with the characteristics of easy metastasis and recurrence,are a serious threat to health of mankind.It is urgent to develop promising clinical cancer targeted agents with combination of rapid diagnosis and efficient therapies.Compared with the conventional photosensitizing agents,the recent advances of nanoagents based on transition metal-oxide clusters possess unique structural and electronic properties,greatly improving cancer survival rate,meanwhile,keeping high contrast imaging.This review provides a brief introduction of metal-oxide clusters,including both nanoclusters to molecular clusters,specifically polyoxometalates(POMs).Subsequently,biocompatibility of metal-oxide clusters is emphasized from aspects of endocytosis,macropinocytosis,and phagocytosis.Through the classification of late and early transition metals oxide clusters,recent outcomes of light-guided nanoagents are represented with their intriguing chemical and optical properties in their diagnosing and photochemotherapy performance.It shed light on the summary of next generation multifunctional cancer targeting agents'developments as well as outlook of materials selection trends and research direction in the future.展开更多
The cancer cells realize their proliferation and metastasis activities based on the special redox adaptation to increased reactive oxygen species(ROS)level,which inversely makes them sensitive to external interference...The cancer cells realize their proliferation and metastasis activities based on the special redox adaptation to increased reactive oxygen species(ROS)level,which inversely makes them sensitive to external interference with their redox state.In view of this,in recent decades,researchers have made great efforts to construct a series of novel nanoplatform-based ROS-mediated cancer therapies through increasing ROS generation and inhibiting the ROS elimination.Besides,the multidrug resistance and thermoresistance of tumor are closely related to tumor redox state.Recently,numerous works have shown that ROS regulation in cancer cells can intervene in the expression,function and stability of related proteins to achieve reversal of tumor resistance.In this review,the recent researches about ROS-regulating nanoagents on cancer therapy and tumor resistance alleviation have been well summarized.Finally,the challenges and research directions of ROS-regulating nanoagents for future clinical translation are also discussed.展开更多
Angiogenesis is critical from early development through the progression of life-threatening diseases.In rheu-matoid arthritis(RA),angiogenesis is markedly heightened and undergoes aberrant changes that exacerbate the ...Angiogenesis is critical from early development through the progression of life-threatening diseases.In rheu-matoid arthritis(RA),angiogenesis is markedly heightened and undergoes aberrant changes that exacerbate the progression of synovitis.However,the intricate mechanisms underlying these changes remain poorly under-stood.Despite the development of numerous anti-angiogenic agents,their clinical efficacy is often compromised by adverse effects and the emergence of adaptive resistance,leading to disease relapse or progression.Nano-medicine has gained significant attention owing to its excellent biocompatibility,precise biological targeting,and enhanced therapeutic outcomes.Anti-angiogenic nanoagents have shown transformative potential in treating cancer and retinal diseases.Nevertheless,a comprehensive review addressing the fundamental mech-anisms of anti-angiogenic nanoagents in RA has yet to be undertaken.Herein,this review provides an in-depth description of the unique structural and functional aspects of pathological angiogenesis in RA and its negative consequences.The mechanisms of pro-angiogenic mediators contributing to RA angiogenesis are further explored.Subsequently,biological activities of nanomedicines for the treatment of RA are summarized.Finally,the cutting-edge developments in the anti-angiogenic nanoagents of RA engineered based on these mechanisms and bioactivities are outlined.A helpful introduction to anti-angiogenic strategies for treatment of RA,which may offer novel perspectives for the development of nanoagents,is opening a new horizon in the fight against RA.展开更多
Antibacterial nanoagents with broad-spectrum antibacterial activities have emerged as an evolution of antibiotics.However,their bacteria-capturing capability and bacteria-killing efficiency remain insufficient for com...Antibacterial nanoagents with broad-spectrum antibacterial activities have emerged as an evolution of antibiotics.However,their bacteria-capturing capability and bacteria-killing efficiency remain insufficient for commercial implementation.Inspired by the hunting behavior of spiders,here,a novel spiderweb-like nanoagent based on silver-adenine nanowires is designed to achieve high-efficiency capture and killing of bacteria.By virtue of the initiative bacteriacapturing functionality,this spiderweb-like nanoagent could effectively attract and trap bacteria through electrostatic interaction and its reticular morphology feature.Furthermore,its synergetic antibacterial mechanism combining physical membranolysis with reactive oxygen species(ROS)release allows such nanoagent to harvest a promoted bactericidal activity.Importantly,the woundplast employing the spiderweblike nanoagent exhibits a superior antibacterial efficacy against drug-resistant Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus compared with commercially available woundplasts.This work may pave a new way for rational design of new generation bactericidal agents facing the future super-bacteria booming.展开更多
基金supported by the National Natural Science Foundation of China(82301104)theNatural Science Foundation of Jiangsu Province(BK20230117)+1 种基金the Natural Science Research Project of Nanjing Polytechnic Institute(NJPI-2023-04)the National Medical Research Council of Singapore(OFIRG21jun-0058 and OFIRG23Jul-0077).
文摘BACKGROUND AND IMPORTANCE Bacterial infections remain a significant public health threat.While antibiotics have mitigated their impact,overuse and misuse have driven the emergence of drug-resistant bacteria,compromising treatment outcomes.Additionally,bacterial biofilms have further diminished the effectiveness of current antibiotics,underscoring the urgent need for new antibacterial therapies.Recent advancements in antibacterial nanoagents,show promise due to their unique physical and chemical properties.These nanoagents have been approved by the US Food and Drug Administration.
基金supported by the National Key R&D Program of China(Intergovernmental Cooperation Project,2017YFE0132200)the National Natural Science Foundation of China(82101032)+2 种基金the Science and Technology Project of Tianjin Health Commission(TJWJ2021MS039)the Fundamental Research Funds for the Central Universities(63223030)the Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-078D).
文摘Phototherapy showed almost a lack of drug resistance and,depending on the therapeutic effects of non-invasive light-stimulating photosensors.The side effects of phototherapy were greatly reduced compared to their traditional equivalents.Phototheranostic nanoagents had new properties in drug delivery,biocompatibility,targeting and response,in which traditional phototheranostic drugs can not possess.Recently,a large number of relevant studies have demonstrated that photodynamic therapy(PDT)in combination with other agents and image-guided multifunctional photothermal therapy(PTT)were well suited for the treatment of oral cancer.Through the design of the nanoagents,researchers have discovered various applications for phototherapy,such as targeted release of co-packaged drugs,multifunctional imaging for diagnosis and treatment combination,accurate targeting caused by nanocarriers,and synergistic chemotherapy with phototherapy.In this paper,we first reviewed the research related to phototheranostic nanoagents for image-guided treatment of oral cancer.We tried to introduce the design concept and the treatment effect by three parts of components of phototheranostic nanoagents,categories of phototheranostic nanoagents and application of phototheranostic nanoagents.It also provided a reference for nanomaterial development and clinical applications in research of oral cancer treatment.
基金The Postdoctoral Fund of Westlake University,Grant/Award Number:103110126582102。
文摘Near-infrared(NIR)absorbing materials hold great potential in biomedical applications,such as fluorescence imaging(FLI),photoacoustic imaging(PAI),photodynamic therapy(PDT),and photothermal therapy(PTT).Generally,these materials can be classified into two main categories based on their absorbing wavelengths:the first NIR(NIR-I)(~650–950 nm)absorbing materials and the second NIR(NIR-Ⅱ)(~1000–1700 nm)absorbing materials.Due to the reduced absorption and scattering of NIR-Ⅱlight in tissue compared to NIR-Ⅰlight,NIR-Ⅱabsorbing materials enable imaging and therapy with improved contrast and deepened penetration,which is in favor of practical applications.Various inorganic materials have been developed for NIR-Ⅱphototheranostics in recent years.However,the non-biodegradability and potential toxicity of these materials hinder their further clinical trans-lation.Biocompatible organic materials with potential biodegradability as well as tailored optical property are thus more desired.In this review,we sum-marize the recent advances of NIR-Ⅱabsorbing organic nanoagents(ONAs)based on small molecules(SMs)and conjugated polymers(CPs)for PAI and PTT and show our perspectives on future challenges and development of these materials.
基金This work was supported by the National Key R&D program of China(2018YFC0115704,2018YFB1105700)the Guangdong Science and Technology Department(2020B1212060018,2020B1212030004)+1 种基金the Guangdong Basic and Applied Basic Research Foundation for Distinguished Young Scholars(2020B1515020027)the grant from Guangzhou Science and Technology Bureau(202002020070,202102010181,202102010007).
文摘The integration of photothermal therapy(PTT)with gene therapy(GT)in a single nanoscale platform demonstrates great potential in cancer therapy.Porous iron oxide nanoagents(PIONs)are widely used as magnetic nanoagents in the drug delivery field and also serve as a photothermal nanoagent for photothermal therapy.However,the therapeutic efficacy of PIONs-mediated GT has not been studied.The long noncoding RNA(lncRNA)CRYBG3(LNC CRYBG3),a lncRNA induced by heavy ion irradiation in lung cancer cells,has been reported to directly bind to globular actin(G-actin)and cause degradation of cytoskeleton and blocking of cytokinesis,thus indicating its potential for use in GT by simulating the effect of heavy ion irradiation and functioning as an antitumor drug.In the present study,we investigated the possibility of combining PIONs-mediated PTT and LNC CRYBG3-mediated GT to destroy non-small cell lung cancer(NSCLC)cells both in vitro and in vivo.The combination therapy showed a high cancer cell killing efficacy,and the cure rate was better than that achieved using PTT or GT alone.Moreover,as a type of magnetic nanoagent,PIONs can be used for magnetic resonance imaging(MRI)and photoacoustic imaging(PAI)both in vitro and in vivo.These findings indicate that the new combination therapy has high potential for cancer treatment.
基金Research and Development Plan of China(No.2016YFA0201500,2020YFA0907702)National Facility for Translational Medi-cine(Shanghai)(No.TMST-2020-001)for financial support.
文摘Affibody molecules are small nonimmunoglobulin affinity proteins,which can precisely target to some cancer cells with specific overexpressed molecular signatures.However,the relatively short in vivo half-life of them seriously limited their application in drug targeted delivery for cancer therapy.Here an amphiphilic affibody-drug conjugate is self-assembled into nanomicelles to prolong circulation time for targeted cancer therapy.As an example of the concept,the nanoagent was prepared through molecular self-assembly of the amphiphilic conjugate of Z_(HHR2:342)-Cys with auristatin E derivate,where the affibody used is capable of binding to the human epidermal growth factor receptor 2(HER2).Such a nanodrug not only increased the blood circulation time,but also enhanced the tumor targeting capacity(abundant affibody arms on the nanoagent surface) and the drug accumulation in tumor.As a result,this affibody-based nanoagent showed excellent antitumor activity in vivo to HER2-positive ovary and breast tumor models,which nearly eradicated both small solid tumors(about 100 mm^(3)) and large established tumors(exceed 500 mm^(3)).The relative tumor proliferation inhibition ratio reaches 99.8% for both models.
基金grants from National Natural Science Foundation of China(No.22101118)Shenyang Bureau of Science and technology(No.RC190167)Natural Science Foundation of Hubei Province(No.2021CFB018)。
文摘Malignant tumors,with the characteristics of easy metastasis and recurrence,are a serious threat to health of mankind.It is urgent to develop promising clinical cancer targeted agents with combination of rapid diagnosis and efficient therapies.Compared with the conventional photosensitizing agents,the recent advances of nanoagents based on transition metal-oxide clusters possess unique structural and electronic properties,greatly improving cancer survival rate,meanwhile,keeping high contrast imaging.This review provides a brief introduction of metal-oxide clusters,including both nanoclusters to molecular clusters,specifically polyoxometalates(POMs).Subsequently,biocompatibility of metal-oxide clusters is emphasized from aspects of endocytosis,macropinocytosis,and phagocytosis.Through the classification of late and early transition metals oxide clusters,recent outcomes of light-guided nanoagents are represented with their intriguing chemical and optical properties in their diagnosing and photochemotherapy performance.It shed light on the summary of next generation multifunctional cancer targeting agents'developments as well as outlook of materials selection trends and research direction in the future.
基金financially supported by the National Key Research and Development Program of China(No.2022YFB3804500)the National Natural Science Foundation of China(NSFC,Nos.51929201 and 52102354)the projects for Science and Technology Development Plan of Jilin province(Nos.20210402046GH and 20220508089RC)。
文摘The cancer cells realize their proliferation and metastasis activities based on the special redox adaptation to increased reactive oxygen species(ROS)level,which inversely makes them sensitive to external interference with their redox state.In view of this,in recent decades,researchers have made great efforts to construct a series of novel nanoplatform-based ROS-mediated cancer therapies through increasing ROS generation and inhibiting the ROS elimination.Besides,the multidrug resistance and thermoresistance of tumor are closely related to tumor redox state.Recently,numerous works have shown that ROS regulation in cancer cells can intervene in the expression,function and stability of related proteins to achieve reversal of tumor resistance.In this review,the recent researches about ROS-regulating nanoagents on cancer therapy and tumor resistance alleviation have been well summarized.Finally,the challenges and research directions of ROS-regulating nanoagents for future clinical translation are also discussed.
基金the National Natural Science Foundation of China,China(82274506,82373871)the Science and Technology Innovation Program of Hunan Province,China,Hunan(2020SK1020,2021RC4035)+6 种基金the Natural Science Foundation of Hunan,China,Hunan(2024JJ5298)the Key Research and Development Pro-gram of Hunan Province,China,Hunan(2024JK2114)the Open-competing Disciple Construction Project of Hunan University of Chinese Medicine(HNUCM),China,Hunan(22JBZ003)the Furong Distinguished Scholar Program of Hunan,China,Hunan(XJT[2020]58)the 121 Training Project for Innovative Talents of Hunan,China,Hunan(XRSH[2019]192)the Chinese Academy of Engineering Academician Liang Liu’s Workstation of HNUCM,China,Hunan(KH[2023]3-23YS001)the World First-class Discipline Incubation Project of HNUCM,China,Hunan(XJF[2022]57).
文摘Angiogenesis is critical from early development through the progression of life-threatening diseases.In rheu-matoid arthritis(RA),angiogenesis is markedly heightened and undergoes aberrant changes that exacerbate the progression of synovitis.However,the intricate mechanisms underlying these changes remain poorly under-stood.Despite the development of numerous anti-angiogenic agents,their clinical efficacy is often compromised by adverse effects and the emergence of adaptive resistance,leading to disease relapse or progression.Nano-medicine has gained significant attention owing to its excellent biocompatibility,precise biological targeting,and enhanced therapeutic outcomes.Anti-angiogenic nanoagents have shown transformative potential in treating cancer and retinal diseases.Nevertheless,a comprehensive review addressing the fundamental mech-anisms of anti-angiogenic nanoagents in RA has yet to be undertaken.Herein,this review provides an in-depth description of the unique structural and functional aspects of pathological angiogenesis in RA and its negative consequences.The mechanisms of pro-angiogenic mediators contributing to RA angiogenesis are further explored.Subsequently,biological activities of nanomedicines for the treatment of RA are summarized.Finally,the cutting-edge developments in the anti-angiogenic nanoagents of RA engineered based on these mechanisms and bioactivities are outlined.A helpful introduction to anti-angiogenic strategies for treatment of RA,which may offer novel perspectives for the development of nanoagents,is opening a new horizon in the fight against RA.
基金supported by the National Natural Science Foundation of China(21703230,21635007 and 21721003)K.C.Wong Education Foundation。
文摘Antibacterial nanoagents with broad-spectrum antibacterial activities have emerged as an evolution of antibiotics.However,their bacteria-capturing capability and bacteria-killing efficiency remain insufficient for commercial implementation.Inspired by the hunting behavior of spiders,here,a novel spiderweb-like nanoagent based on silver-adenine nanowires is designed to achieve high-efficiency capture and killing of bacteria.By virtue of the initiative bacteriacapturing functionality,this spiderweb-like nanoagent could effectively attract and trap bacteria through electrostatic interaction and its reticular morphology feature.Furthermore,its synergetic antibacterial mechanism combining physical membranolysis with reactive oxygen species(ROS)release allows such nanoagent to harvest a promoted bactericidal activity.Importantly,the woundplast employing the spiderweblike nanoagent exhibits a superior antibacterial efficacy against drug-resistant Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus compared with commercially available woundplasts.This work may pave a new way for rational design of new generation bactericidal agents facing the future super-bacteria booming.
