We prepared biocompatible and environment-friendly zinc oxide nanoparticles(ZnO NPs)with upconversion properties and catalase-like nanozyme activity.Photodynamic therapy(PDT)application is severely limited by the poor...We prepared biocompatible and environment-friendly zinc oxide nanoparticles(ZnO NPs)with upconversion properties and catalase-like nanozyme activity.Photodynamic therapy(PDT)application is severely limited by the poor penetration of UV-Visible light and a hypoxic tumor environment.Here,we used ZnO NPs as a carrier for the photosensitizer chlorin e6(Ce6)to construct zinc oxide-chlorin e6 nanoparticles(ZnO-Ce6 NPs),simultaneously addressing both problems.In terms of penetration,ZnO NPs convert 808 nm near-infrared light into 401 nm visible light to excite Ce6,achieving deep-penetrating photodynamic therapy under long-wavelength light.Interestingly,the ability to emit short-wavelength light under long-wavelength light is usually observed in upconversion nanoparticles.As nanozymes,ZnO NPs can catalyze the decomposition of hydrogen peroxide in tumors,providing oxygen for photodynamic action and relieving hypoxia.The enhanced photodynamic action produces a large amount of reactive oxygen species,which overactivate autophagy and trigger immunogenic cell death(ICD),leading to antitumor immunotherapy.In addition,even in the absence of light,ZnO and ZnO-Ce6 NPs can induce ferroptosis of tumor cells and exert antitumor effects.展开更多
Photodynamic therapy(PDT)is a promising strategy for tumor treatment.Still,its therapeutic efficacy is compromised by the unsatisfactory cytotoxicity to specific subcellular organelles and insidious tumor microenviron...Photodynamic therapy(PDT)is a promising strategy for tumor treatment.Still,its therapeutic efficacy is compromised by the unsatisfactory cytotoxicity to specific subcellular organelles and insidious tumor microenvironment properties like hypoxia and high glutathione levels.Here,we fabricated a novel nanoenzyme that derived from metal-organic framework(MOF)with intrinsic catalase-like activities to decompose H2O2 to O2 and simultaneous glutathione consumption for enhancing PDT efficacy.The obtained Mn3O4 nanoparticle shows a larger pore size and surface area compared to native MOF particles,which can be used to load high dose photosensitizer.When decorated with AS1411 aptamer and polyethylene glycol(PEG),the obtained Mn3O4-PEG@C&A particle exhibits excellent stability and cell nucleus targeting ability.Remarkably,Mn3O4-PEG@C&A particle inhibited the tumor growth in the mouse model with high efficacy without any biotoxicity.This is the first report that applied MOF-derived nanoparticle to nucleus-targeted PDT.It may provide a new approach for designing functional nanoenzyme to subcellular organelles-targeted tumor modulation.展开更多
Magnetite nanoparticles （Fe3O4 NPs） are a well proven biocompatible nanomaterial, which hold great promise in various biomedical applications. Interestingly, unlike conventional biocompatible materials （e.g., polye...Magnetite nanoparticles （Fe3O4 NPs） are a well proven biocompatible nanomaterial, which hold great promise in various biomedical applications. Interestingly, unlike conventional biocompatible materials （e.g., polyethylene glycol （PEG）） that are chemically and biologically inert in nature, Fe3O4 NPs are known to be catalytically active and exhibit prominent physiological effects. Herein, we report an ＂active＂, dynamic equilibrium mechanism for maintaining the cellular amenity of Fe3O4 NPs. We examined the effects of two types of iron oxide （magnetite and hematite） NPs in rat pheochromocytoma （PC12） cells and found that both induced stress responses. However, only Fe2O3 NPs caused significant programmed cell death; whereas Fe3O4 NPs are amenable to cells. We found that intrinsic catalase-like activity of Fe3O4 NPs antagonized the accumulation of toxic reactive oxygen species （ROS） induced by themselves, and thereby modulated the extent of cellular oxidative stress, autophagic activity, and programmed cell death. In line with this observation, we effectively reversed severe autophagy and cell death caused by Fe2O3 NPs via co-treatment with natural catalase. This study not only deciphers the distinct intrinsic antagonism of Fe3O4 NPs, but opens new routes to designing biocompatible theranostic nanoparticles with novel mechanisms.展开更多
Adenosine triphosphate(ATP)is produced mainly in the mitochondrion,and its primary task is to function as a ubiquitous energy currency to meet the cellular metabolic demands in biological systems.Thus far,its potentia...Adenosine triphosphate(ATP)is produced mainly in the mitochondrion,and its primary task is to function as a ubiquitous energy currency to meet the cellular metabolic demands in biological systems.Thus far,its potential role as performing enzymatic functions has not been elucidated.展开更多
基金support from the National Natural Science Foundation of China(No.81773646)the National Key Research and Development Program of China(2017YFA0205600)the Innovation Team of the Ministry of Education(No.BMU2017TD003,China).
文摘We prepared biocompatible and environment-friendly zinc oxide nanoparticles(ZnO NPs)with upconversion properties and catalase-like nanozyme activity.Photodynamic therapy(PDT)application is severely limited by the poor penetration of UV-Visible light and a hypoxic tumor environment.Here,we used ZnO NPs as a carrier for the photosensitizer chlorin e6(Ce6)to construct zinc oxide-chlorin e6 nanoparticles(ZnO-Ce6 NPs),simultaneously addressing both problems.In terms of penetration,ZnO NPs convert 808 nm near-infrared light into 401 nm visible light to excite Ce6,achieving deep-penetrating photodynamic therapy under long-wavelength light.Interestingly,the ability to emit short-wavelength light under long-wavelength light is usually observed in upconversion nanoparticles.As nanozymes,ZnO NPs can catalyze the decomposition of hydrogen peroxide in tumors,providing oxygen for photodynamic action and relieving hypoxia.The enhanced photodynamic action produces a large amount of reactive oxygen species,which overactivate autophagy and trigger immunogenic cell death(ICD),leading to antitumor immunotherapy.In addition,even in the absence of light,ZnO and ZnO-Ce6 NPs can induce ferroptosis of tumor cells and exert antitumor effects.
基金We gratefully acknowledge the financial support from National Natural Science Foundation of China(Nos.21775049,31700746,31870856 and 31870854)National Key R&D Program of China(Nos.2017YFA0700403 and 2016YFF0100801)China Postdoctoral Science Foundation funded project(Nos.2018M630847 and 2018T110753).
文摘Photodynamic therapy(PDT)is a promising strategy for tumor treatment.Still,its therapeutic efficacy is compromised by the unsatisfactory cytotoxicity to specific subcellular organelles and insidious tumor microenvironment properties like hypoxia and high glutathione levels.Here,we fabricated a novel nanoenzyme that derived from metal-organic framework(MOF)with intrinsic catalase-like activities to decompose H2O2 to O2 and simultaneous glutathione consumption for enhancing PDT efficacy.The obtained Mn3O4 nanoparticle shows a larger pore size and surface area compared to native MOF particles,which can be used to load high dose photosensitizer.When decorated with AS1411 aptamer and polyethylene glycol(PEG),the obtained Mn3O4-PEG@C&A particle exhibits excellent stability and cell nucleus targeting ability.Remarkably,Mn3O4-PEG@C&A particle inhibited the tumor growth in the mouse model with high efficacy without any biotoxicity.This is the first report that applied MOF-derived nanoparticle to nucleus-targeted PDT.It may provide a new approach for designing functional nanoenzyme to subcellular organelles-targeted tumor modulation.
基金We would like to dedicate this article to Professor Qing Huang. This work was supported by National Natural Science Foundation of China （Nos. 31771102, 31371015, 21675167, U1532119, 31470970, 31371493, and 31571498）, the National Basic Research Program of China （Nos. 2013CB932803, 2013CB933802, 2016YFA0400900, and 2016YFA0201200）, the Youth Innovation Promotion Association from Chinese Academy of Sciences （No. 2015211）, Key Research Program of Frontier Sciences, CAS （Nos. QYZDJ-SSW-SLH019 and QYZDJ-SSW-SLH031）.
文摘Magnetite nanoparticles （Fe3O4 NPs） are a well proven biocompatible nanomaterial, which hold great promise in various biomedical applications. Interestingly, unlike conventional biocompatible materials （e.g., polyethylene glycol （PEG）） that are chemically and biologically inert in nature, Fe3O4 NPs are known to be catalytically active and exhibit prominent physiological effects. Herein, we report an ＂active＂, dynamic equilibrium mechanism for maintaining the cellular amenity of Fe3O4 NPs. We examined the effects of two types of iron oxide （magnetite and hematite） NPs in rat pheochromocytoma （PC12） cells and found that both induced stress responses. However, only Fe2O3 NPs caused significant programmed cell death; whereas Fe3O4 NPs are amenable to cells. We found that intrinsic catalase-like activity of Fe3O4 NPs antagonized the accumulation of toxic reactive oxygen species （ROS） induced by themselves, and thereby modulated the extent of cellular oxidative stress, autophagic activity, and programmed cell death. In line with this observation, we effectively reversed severe autophagy and cell death caused by Fe2O3 NPs via co-treatment with natural catalase. This study not only deciphers the distinct intrinsic antagonism of Fe3O4 NPs, but opens new routes to designing biocompatible theranostic nanoparticles with novel mechanisms.
基金This work was supported by the research grants from the National Natural Science Foundation of China(nos.21405124 and 21175110)Fundamental Research Funds for the Central Universities(no.XDJK2017D052).
文摘Adenosine triphosphate(ATP)is produced mainly in the mitochondrion,and its primary task is to function as a ubiquitous energy currency to meet the cellular metabolic demands in biological systems.Thus far,its potential role as performing enzymatic functions has not been elucidated.
