Nanoenzyme-mediated antibacterial strategies have been widely exploited to overcome the shortcomings(such as drug resistance and mild-to-severe side effects) of antibiotic therapy.The peroxidase-like activity of nanoe...Nanoenzyme-mediated antibacterial strategies have been widely exploited to overcome the shortcomings(such as drug resistance and mild-to-severe side effects) of antibiotic therapy.The peroxidase-like activity of nanoenzymes possesses great potential against bacterial infection by the generation of hydroxyl radical(·OH) in the specific microenvironment.However,the lifetime of-OH is extremely short,and a large amount of the ·OH generated within the infection microenvironment cannot come into contact with bacteria quickly enough,thus resulting in low treatment efficiency.Here,chitosan-oligosaccharide-modified CuS nanoparticles possessing positive charges(PCuS NPs) were prepared using a one-pot method.PCuS NPs exhibited efficient peroxidase-like activity.Importantly,the PCuS NPs can combine with bacteria via electrostatic attraction.The direct contact between the PCuS NPs and bacteria enabled the generation of ·OH in situ on the bacterial surface,ultimately leading to a high antibacterial efficacy at a low concentration in the presence of H_(2)O_(2).At an effective antibacterial concentration,the PCuS NPs exhibited high cytocompatibility.Furthermore,in vivo results revealed that PCuS NPs not only decreased the size of abscesses but also reduced inflammation and promoted collagen fiber formation.Therefore,PCuS NPs possess great potential against bacterial infection via in situ ·OH generation based on electrostatic attraction.展开更多
The use of magneto-mechanical force to kill cancer cells has attracted significant attention in recent years.However,many reports have focused on in vitro experiments with a single treatment.Herein,CaO_(2)-coated Fe_(...The use of magneto-mechanical force to kill cancer cells has attracted significant attention in recent years.However,many reports have focused on in vitro experiments with a single treatment.Herein,CaO_(2)-coated Fe_(3)O_(4)core–shell magnetic nanoenzymes(Fe_(3)O_(4)/CaO_(2))are developed for low frequency vibrating magnetic field(VMF)-induced multimodal cancer therapy.Fe_(3)O_(4)/CaO_(2)are shown to efficiently generate O_(2),H_(2)O_(2),·OH through hydrolysis of CaO_(2)and a CaO_(2)-strengthened Fenton reaction,killing laryngeal carcinoma cells and inhibiting mouse tumor growth(chemodynamic therapy(CDT)).Both Fe_(3)O_(4)and Fe_(3)O_(4)/CaO_(2)triggered by a VMF are shown to damage the cytoskeleton of cancer cells through magneto-mechanical force(maxima:223 piconewtons or larger by Fe_(3)O_(4)/CaO_(2)aggregations)and induce the generation of intracellular reactive oxygen species(ROS),the VMF-triggered Fe_(3)O_(4)/CaO_(2)is shown to generate additional intracellular ROS.Upon exposure to a VMF,the cell killing efficiency and tumor growth inhibition were further significantly improved by Fe_(3)O_(4)/CaO_(2)through CDT,magnetomechanical force,force-induced ROS,the cytotoxicity of Ca^(2+)ions.In addition,the Fe_(3)O_(4)/CaO_(2)nanoenzymes and VMFinduced treatment are shown to be safe for mice.The results of this study open the door for treating solid tumors without inducing multidrug resistance through the combination of CDT and force.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
Bone injury and implantation operation are often accompanied by microenvironment damage of bone tis-sue,which seriously affects the process of osseointegration of implants,especially for titanium(Ti)-based bioinert ma...Bone injury and implantation operation are often accompanied by microenvironment damage of bone tis-sue,which seriously affects the process of osseointegration of implants,especially for titanium(Ti)-based bioinert materials.Thus,repairing or improving the microenvironment of damaged bone tissue is of great significance for bone rescue,reconstruction,and regeneration,which is still a major medical challenge.Oxidative stress(OS)and oxygen(O_(2))deficiency are considered to be specific physiological signals of the bone-injury microenvironment.From the above background,a coating consisting of manganese dioxide(MnO_(2))nanoenzyme and strontium(Sr)ions was fabricated on the surface of the Ti implant via a one-step hydrothermal treatment.MnO_(2) nanoenzyme presented in the coating alleviated OS and O_(2) deficiency at the injury site by catalyzing the decomposition of abundant endogenous H_(2)O_(2) around the modified Ti implants into O_(2).In addition,Sr ions were released from the surface of the implant at a certain rate in a body-fluid environment,further promoting the adhesion,growth,and osteogenic differentiation of mesenchymal stem cells.More importantly,a Sprague Dawley rat femur model demonstrated that the modified Ti implant showed significant potential to accelerate bone tissue reconstruction in vivo.In sum-mary,the present system provides a new idea for the treatment of bone injury and the development of new orthopedic implants.展开更多
The development of high-efficiency peroxidase mimetics is highly desirable in view of high cost and low stability of natural enzymes.From the perspective of mimicking active site microenvironment at low cost,we herein...The development of high-efficiency peroxidase mimetics is highly desirable in view of high cost and low stability of natural enzymes.From the perspective of mimicking active site microenvironment at low cost,we herein report a novel histidine-functionalized graphene quantum dot(His-GQD)/hemin complex,which exhibits the highest catalytic rate for the peroxidase-based chromogenic reaction among the hemin-containing mimetics reported so far.Also,our peroxidase mimetic shows excellent tolerance to strongly acidic conditions and can function in a wide temperature range.Lineweaver-Burk plots and comprehensive electron paramagnetic resonance analysis reveal a ping-pong type catalytic mechanism for this mimetic.In addition,His-GQD/hemin demonstrates high efficiency and accuracy in detecting H2O2 and blood glucose.Our work provides an effective design of artificial enzymes for practical applications.展开更多
Artificial nanoenzymes with enzyme-like catalytic activity have gradually become an alternative to natural enzymes due to their low production cost,high stability,and good tolerance.In recent years,various enzyme mimi...Artificial nanoenzymes with enzyme-like catalytic activity have gradually become an alternative to natural enzymes due to their low production cost,high stability,and good tolerance.In recent years,various enzyme mimics have emerged with the rapid development of nano-teclnology.Metal-organic frameworks(MOFs)are a novel class of porous inorganic-organic hybrid materials made from metal ions/clusters and organic ligands,and MOFs-based nanozymes show great prospect in biosensing,biocatalysis,biomedical imaging,and therapeutic applications,due to unique properties,such as high specific surface area,high porosity,tunable morphology,and excellent biocatalytic properties.In this paper,the recent progresses concerning MOFs-based nanozymes are systematically summarized,including the synthesis,design strategies and related applications,which are divided into two major categories,namely,MOFs structured nanoenzymes and MOFs composite structured nanoenzymes.Meanwhile,the applications of various classifications of MOFs research are introduced.At the end,current challenges and future perspectives of MOFs-based nanozymes are also discussed.It is highly expected that this review on this important area can provide a meaningful guidance for tumor therapy,biosensing and other aspects.展开更多
Graphitic carbon nitride(g-C3 N4),as a visible-light-active organic semiconductor,has attracted growing attentions in photocatalysis and photoluminescence-based biosensing.Here,we demonstrated the intrinsic photooxida...Graphitic carbon nitride(g-C3 N4),as a visible-light-active organic semiconductor,has attracted growing attentions in photocatalysis and photoluminescence-based biosensing.Here,we demonstrated the intrinsic photooxidase activity of g-C3 N4 and then surface molecular imprinting on g-C3 N4 nanozymes was achieved for improved biosensing.Upon blue LED irradiation,the g-C3 N4 exhibited superior enzymatic activity for oxidation of chromogenic substrate like 3,3’,5,5’-tetramethylbenzidine(TMB)without destructive H2 O2.The oxidation was mainly ascribed to ·O2^-that was generated during light irradiation.The surface molecular imprinting on g-C3 N4 can lead to an over 1000-fold alleviation in matrix-interference from serum samples,4-fold improved enzymatic activity as well as enhanced substrate specificity comparing with bare g-C3 N4 during colorimetric sensing.Also,the MIP-g-C3 N4 possesses a high affinity to TMB with a Km value of only 22 μmol/L,much lower than other comment nanozymes like AuNPs,Fe3 O4 NPs,etc.It was successfully applied for detection of cysteine in serum sample with satisfactory recoveries.展开更多
基金financially supported by the National Natural Science Foundation of China (No.82100974)the Natural Science Foundation of Shandong Province (No.ZR2021QH241)Qilu Young Scholars Program of Shandong University。
文摘Nanoenzyme-mediated antibacterial strategies have been widely exploited to overcome the shortcomings(such as drug resistance and mild-to-severe side effects) of antibiotic therapy.The peroxidase-like activity of nanoenzymes possesses great potential against bacterial infection by the generation of hydroxyl radical(·OH) in the specific microenvironment.However,the lifetime of-OH is extremely short,and a large amount of the ·OH generated within the infection microenvironment cannot come into contact with bacteria quickly enough,thus resulting in low treatment efficiency.Here,chitosan-oligosaccharide-modified CuS nanoparticles possessing positive charges(PCuS NPs) were prepared using a one-pot method.PCuS NPs exhibited efficient peroxidase-like activity.Importantly,the PCuS NPs can combine with bacteria via electrostatic attraction.The direct contact between the PCuS NPs and bacteria enabled the generation of ·OH in situ on the bacterial surface,ultimately leading to a high antibacterial efficacy at a low concentration in the presence of H_(2)O_(2).At an effective antibacterial concentration,the PCuS NPs exhibited high cytocompatibility.Furthermore,in vivo results revealed that PCuS NPs not only decreased the size of abscesses but also reduced inflammation and promoted collagen fiber formation.Therefore,PCuS NPs possess great potential against bacterial infection via in situ ·OH generation based on electrostatic attraction.
基金the National Natural Science Foundation of China(No.31570960)Open Funding Project of the State Key Laboratory of Bioreactor Engineering.
文摘The use of magneto-mechanical force to kill cancer cells has attracted significant attention in recent years.However,many reports have focused on in vitro experiments with a single treatment.Herein,CaO_(2)-coated Fe_(3)O_(4)core–shell magnetic nanoenzymes(Fe_(3)O_(4)/CaO_(2))are developed for low frequency vibrating magnetic field(VMF)-induced multimodal cancer therapy.Fe_(3)O_(4)/CaO_(2)are shown to efficiently generate O_(2),H_(2)O_(2),·OH through hydrolysis of CaO_(2)and a CaO_(2)-strengthened Fenton reaction,killing laryngeal carcinoma cells and inhibiting mouse tumor growth(chemodynamic therapy(CDT)).Both Fe_(3)O_(4)and Fe_(3)O_(4)/CaO_(2)triggered by a VMF are shown to damage the cytoskeleton of cancer cells through magneto-mechanical force(maxima:223 piconewtons or larger by Fe_(3)O_(4)/CaO_(2)aggregations)and induce the generation of intracellular reactive oxygen species(ROS),the VMF-triggered Fe_(3)O_(4)/CaO_(2)is shown to generate additional intracellular ROS.Upon exposure to a VMF,the cell killing efficiency and tumor growth inhibition were further significantly improved by Fe_(3)O_(4)/CaO_(2)through CDT,magnetomechanical force,force-induced ROS,the cytotoxicity of Ca^(2+)ions.In addition,the Fe_(3)O_(4)/CaO_(2)nanoenzymes and VMFinduced treatment are shown to be safe for mice.The results of this study open the door for treating solid tumors without inducing multidrug resistance through the combination of CDT and force.
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financially supported by the National Natu-ral Science Foundation of China (Nos.32171327,21734002,and 51825302)the Natural Science Foundation of Chongqing (No.cstc2021jcyj-cxttX0002).
文摘Bone injury and implantation operation are often accompanied by microenvironment damage of bone tis-sue,which seriously affects the process of osseointegration of implants,especially for titanium(Ti)-based bioinert materials.Thus,repairing or improving the microenvironment of damaged bone tissue is of great significance for bone rescue,reconstruction,and regeneration,which is still a major medical challenge.Oxidative stress(OS)and oxygen(O_(2))deficiency are considered to be specific physiological signals of the bone-injury microenvironment.From the above background,a coating consisting of manganese dioxide(MnO_(2))nanoenzyme and strontium(Sr)ions was fabricated on the surface of the Ti implant via a one-step hydrothermal treatment.MnO_(2) nanoenzyme presented in the coating alleviated OS and O_(2) deficiency at the injury site by catalyzing the decomposition of abundant endogenous H_(2)O_(2) around the modified Ti implants into O_(2).In addition,Sr ions were released from the surface of the implant at a certain rate in a body-fluid environment,further promoting the adhesion,growth,and osteogenic differentiation of mesenchymal stem cells.More importantly,a Sprague Dawley rat femur model demonstrated that the modified Ti implant showed significant potential to accelerate bone tissue reconstruction in vivo.In sum-mary,the present system provides a new idea for the treatment of bone injury and the development of new orthopedic implants.
基金The authors acknowledge financial support for this work from the National Key R&D Program"nanotechnology"special focus(No.2016YFA0201600)the National Natural Science Foundation of China(Nos.21422303,21573049,21872043,81602643)+1 种基金Beijing Natural Science Foundation(No.2142036)the Knowledge Innovation Program,Youth Innovation Promotion Association,and Special Program of"One Belt One Road"of CAS.The authors thank Dr.Dexing Li for the technique support and many helpful discussions for the ITC testing.
文摘The development of high-efficiency peroxidase mimetics is highly desirable in view of high cost and low stability of natural enzymes.From the perspective of mimicking active site microenvironment at low cost,we herein report a novel histidine-functionalized graphene quantum dot(His-GQD)/hemin complex,which exhibits the highest catalytic rate for the peroxidase-based chromogenic reaction among the hemin-containing mimetics reported so far.Also,our peroxidase mimetic shows excellent tolerance to strongly acidic conditions and can function in a wide temperature range.Lineweaver-Burk plots and comprehensive electron paramagnetic resonance analysis reveal a ping-pong type catalytic mechanism for this mimetic.In addition,His-GQD/hemin demonstrates high efficiency and accuracy in detecting H2O2 and blood glucose.Our work provides an effective design of artificial enzymes for practical applications.
基金supported by the National Natural Science Foundation of China (Nos.52050077,82073475)the Natural Science Foundation of Jilin Province,China (No.20210401059YY).
文摘Artificial nanoenzymes with enzyme-like catalytic activity have gradually become an alternative to natural enzymes due to their low production cost,high stability,and good tolerance.In recent years,various enzyme mimics have emerged with the rapid development of nano-teclnology.Metal-organic frameworks(MOFs)are a novel class of porous inorganic-organic hybrid materials made from metal ions/clusters and organic ligands,and MOFs-based nanozymes show great prospect in biosensing,biocatalysis,biomedical imaging,and therapeutic applications,due to unique properties,such as high specific surface area,high porosity,tunable morphology,and excellent biocatalytic properties.In this paper,the recent progresses concerning MOFs-based nanozymes are systematically summarized,including the synthesis,design strategies and related applications,which are divided into two major categories,namely,MOFs structured nanoenzymes and MOFs composite structured nanoenzymes.Meanwhile,the applications of various classifications of MOFs research are introduced.At the end,current challenges and future perspectives of MOFs-based nanozymes are also discussed.It is highly expected that this review on this important area can provide a meaningful guidance for tumor therapy,biosensing and other aspects.
基金the financial support from the National Natural Science Foundation of China(No.21475013)the Sichuan Science and Technology Project(No.2018JY0466)
文摘Graphitic carbon nitride(g-C3 N4),as a visible-light-active organic semiconductor,has attracted growing attentions in photocatalysis and photoluminescence-based biosensing.Here,we demonstrated the intrinsic photooxidase activity of g-C3 N4 and then surface molecular imprinting on g-C3 N4 nanozymes was achieved for improved biosensing.Upon blue LED irradiation,the g-C3 N4 exhibited superior enzymatic activity for oxidation of chromogenic substrate like 3,3’,5,5’-tetramethylbenzidine(TMB)without destructive H2 O2.The oxidation was mainly ascribed to ·O2^-that was generated during light irradiation.The surface molecular imprinting on g-C3 N4 can lead to an over 1000-fold alleviation in matrix-interference from serum samples,4-fold improved enzymatic activity as well as enhanced substrate specificity comparing with bare g-C3 N4 during colorimetric sensing.Also,the MIP-g-C3 N4 possesses a high affinity to TMB with a Km value of only 22 μmol/L,much lower than other comment nanozymes like AuNPs,Fe3 O4 NPs,etc.It was successfully applied for detection of cysteine in serum sample with satisfactory recoveries.
