Diabetic wounds(DWs)are a major complication of diabetes mellitus,characterized by a complex patho-physiological microenvironment that is associated with elevated morbidity and mortality.Conventional management strate...Diabetic wounds(DWs)are a major complication of diabetes mellitus,characterized by a complex patho-physiological microenvironment that is associated with elevated morbidity and mortality.Conventional management strategies often fail to address the multifaceted nature of these wounds effectively.Recent advancements in understanding the mechanisms of DW healing have spurred the development of a plethora of bioactive dressings designed to interact with and modulate the DW microenvironment.These innovations have culminated in the introduction of the“microenvironment-sensitive with on-demand management”paradigm aimed at delivering precision therapy responsive to dynamic changes within DW.Despite these advancements,the current literature lacks a comprehensive review that cate-gorizes and evaluates active,passive,and on-demand approaches that address the DW microenviron-ment.Herein,we describe the unique pathogenic mechanisms and microenvironmental characteristics that distinguish DW from normal acute wounds.This review provides an extensive overview of contem-porary active and passive management strategies incorporating on-demand management principles designed for DW microenvironments.Furthermore,it addresses the principal challenges faced in this therapeutic domain and outlines the potential innovations that can enhance the efficacy and specificity of bioactive dressings.The insights presented here aim to guide further research and development in the on-demand management of DW to improve patient outcomes by aligning personalized therapy modali-ties with the pathophysiological realities of DW.展开更多
Nanoparticles that employ stimuli-responsive polymeric delivery carriers have emerged as intelligent nanoplatforms with great potential in cancer theranostics,mainly including cancer diagnosis,controlled/triggered dru...Nanoparticles that employ stimuli-responsive polymeric delivery carriers have emerged as intelligent nanoplatforms with great potential in cancer theranostics,mainly including cancer diagnosis,controlled/triggered drug delivery,and real-time monitoring of therapeutic response.Particularly,tumor microenvironment(TME)-responsive polymeric nanocarriers in response to weak acidity,hypoxia,reactive oxygen species(ROS),glutathione(GSH),or tumor enzymes in the TME show great promise in facilitating tumor accumulation,enhancing tumor penetration,prolonging tumor retention,and achieving controlled drug release,thereby improving the efficiency of tumor therapy.Besides,the combination of chemotherapy and phototherapy presents a promising endeavor for the treatment of tumors,which allows for the integration of the advantages of each treatment modality,addressing the shortcomings of the two methods,and amplifying the efficacy of tumor treatment while reducing adverse reactions.This review focuses on the latest progress in the development of TME-responsive polymeric nanoparticles for synergetic chemo-photo therapy,and discusses the critical challenges and future considerations involved in the fabrication of TME-responsive nanocarriers.展开更多
Carbon monoxide (CO) therapy has emerged asa promising approach in cancer treatment. Selecting suitablenanocarriers for delivering manganese carbonyl (MnCO), aCO donor, while simultaneously regulating CO release andco...Carbon monoxide (CO) therapy has emerged asa promising approach in cancer treatment. Selecting suitablenanocarriers for delivering manganese carbonyl (MnCO), aCO donor, while simultaneously regulating CO release andcompensating for hydrogen peroxide (H2O2) and acidity in thetumor microenvironment is crucial for enhancing the effectivenessof CO therapy. In this study, a tumor microenvironment-responsive core-shell structured cascade nanoreactorwas designed and synthesized using mesoporous polydopamine(MPDA) as a nanocarrier, followed by loading ofMnCO and glucose oxidase-encapsulated zeolite imidazolateframework-8 (GOx@ZIF-8) nanoparticles. Upon enteringcancer cells, the protective shell of GOx@ZIF-8 degrades inresponse to the acidic tumor environment, releasing GOx.GOx catalyzes the conversion of endogenous glucose intogluconic acid and H2O2, accelerating energy starvation in tumorcells. This process, in turn, promotes the reaction betweenMnCO and H2O2, resulting in in-situ amplified release of CO.Additionally, the excellent photothermal properties of MPDAenable photothermal therapy. This comprehensive antitumorstrategy represents a promising advancement in the field ofCO-based cancer therapy.展开更多
基金supported by the National Natural Science Foundation of China(22408078,82401057,32101170)the Zhejiang Province Postdoctoral Excellence Funding Program-Special Support(ZJ2024004).
文摘Diabetic wounds(DWs)are a major complication of diabetes mellitus,characterized by a complex patho-physiological microenvironment that is associated with elevated morbidity and mortality.Conventional management strategies often fail to address the multifaceted nature of these wounds effectively.Recent advancements in understanding the mechanisms of DW healing have spurred the development of a plethora of bioactive dressings designed to interact with and modulate the DW microenvironment.These innovations have culminated in the introduction of the“microenvironment-sensitive with on-demand management”paradigm aimed at delivering precision therapy responsive to dynamic changes within DW.Despite these advancements,the current literature lacks a comprehensive review that cate-gorizes and evaluates active,passive,and on-demand approaches that address the DW microenviron-ment.Herein,we describe the unique pathogenic mechanisms and microenvironmental characteristics that distinguish DW from normal acute wounds.This review provides an extensive overview of contem-porary active and passive management strategies incorporating on-demand management principles designed for DW microenvironments.Furthermore,it addresses the principal challenges faced in this therapeutic domain and outlines the potential innovations that can enhance the efficacy and specificity of bioactive dressings.The insights presented here aim to guide further research and development in the on-demand management of DW to improve patient outcomes by aligning personalized therapy modali-ties with the pathophysiological realities of DW.
基金supported by National Key Clinical Specialties Construction Programthe National Natural Science Foundation of China(No.81602699)the Sichuan Science and Technology program(No.2019YFG0266)。
文摘Nanoparticles that employ stimuli-responsive polymeric delivery carriers have emerged as intelligent nanoplatforms with great potential in cancer theranostics,mainly including cancer diagnosis,controlled/triggered drug delivery,and real-time monitoring of therapeutic response.Particularly,tumor microenvironment(TME)-responsive polymeric nanocarriers in response to weak acidity,hypoxia,reactive oxygen species(ROS),glutathione(GSH),or tumor enzymes in the TME show great promise in facilitating tumor accumulation,enhancing tumor penetration,prolonging tumor retention,and achieving controlled drug release,thereby improving the efficiency of tumor therapy.Besides,the combination of chemotherapy and phototherapy presents a promising endeavor for the treatment of tumors,which allows for the integration of the advantages of each treatment modality,addressing the shortcomings of the two methods,and amplifying the efficacy of tumor treatment while reducing adverse reactions.This review focuses on the latest progress in the development of TME-responsive polymeric nanoparticles for synergetic chemo-photo therapy,and discusses the critical challenges and future considerations involved in the fabrication of TME-responsive nanocarriers.
基金supported by the National Natural Science Foundation of China (21971153 and 22371172)the Major Basic Research Projects of Shandong Provincial Natural Science Foundation (ZR2020ZD32)+2 种基金the Taishan Scholars Climbing Program of Shandong Provincethe Natural Science Foundation of Shandong Province (ZR2021QB035)the financial support from the China Scholarship Council (202108370157)。
文摘Carbon monoxide (CO) therapy has emerged asa promising approach in cancer treatment. Selecting suitablenanocarriers for delivering manganese carbonyl (MnCO), aCO donor, while simultaneously regulating CO release andcompensating for hydrogen peroxide (H2O2) and acidity in thetumor microenvironment is crucial for enhancing the effectivenessof CO therapy. In this study, a tumor microenvironment-responsive core-shell structured cascade nanoreactorwas designed and synthesized using mesoporous polydopamine(MPDA) as a nanocarrier, followed by loading ofMnCO and glucose oxidase-encapsulated zeolite imidazolateframework-8 (GOx@ZIF-8) nanoparticles. Upon enteringcancer cells, the protective shell of GOx@ZIF-8 degrades inresponse to the acidic tumor environment, releasing GOx.GOx catalyzes the conversion of endogenous glucose intogluconic acid and H2O2, accelerating energy starvation in tumorcells. This process, in turn, promotes the reaction betweenMnCO and H2O2, resulting in in-situ amplified release of CO.Additionally, the excellent photothermal properties of MPDAenable photothermal therapy. This comprehensive antitumorstrategy represents a promising advancement in the field ofCO-based cancer therapy.
