The current single-atom catalysts(SACs)for medicine still suffer from the limited active site density.Here,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs ...The current single-atom catalysts(SACs)for medicine still suffer from the limited active site density.Here,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with iron.The constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial effects.Attractively,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading SACs.Consequently,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/C.In addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)depletion.Both in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound healing.This work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.展开更多
Nanocatalytic therapy shows great potential for therapeutic interventions.However,therapeutic efficiency is often limited by unsatisfactory enzyme activity and lack of the coordination of immune system.Therefore,engin...Nanocatalytic therapy shows great potential for therapeutic interventions.However,therapeutic efficiency is often limited by unsatisfactory enzyme activity and lack of the coordination of immune system.Therefore,engineering nanozymes activity enhancement while activating immune system will be an effective strategy to achieve efficient tumor therapy.Herein,we synthesize a DSPE-PEG-FA modified manganese dioxide-based dual-atom nanozyme(MDF),on which iridium and platinum atoms are anchored.The obtained MDF can simultaneously mimic four enzyme activities of catalase,oxidase,peroxidase,and glutathione oxidase,set off a reactive oxygen species(ROS)storm,cause tumor cell death.The enzyme activity of MDF can be enhanced by its own photothermal effect.Meanwhile,MDF can consume intracellular glutathione and release Mn^(2+),which can prevent generated ROS from consumption and further activate cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes(cGAS-STING)pathway and promote the secretion of type I interferon,which will help promote dendritic cells maturation,present antigens to T lymphocytes to help kill tumor cells.Ultimately,MDF shows excellent tumor suppressive effects.This work provides a new paradigm for the field of nanozymes and offers a new reference for involvement of cGAS-STING pathway activation in tumor catalytic therapy.展开更多
The low immunogenicity of tumors remains one of the major limitations of cancer immunotherapy.Herein,we report a bacterial metabolisminitiated and photothermal-enhanced nanocatalytic therapy strategy to completely era...The low immunogenicity of tumors remains one of the major limitations of cancer immunotherapy.Herein,we report a bacterial metabolisminitiated and photothermal-enhanced nanocatalytic therapy strategy to completely eradicate primary tumor by triggering highly effective antitumor immune responses.Briefly,a microbiotic nanomedicine,designated as Cu_(2)O@ΔSt,has been constructed by conjugating PEGylated Cu_(2)O nanoparticles on the surface of an engineered Salmonella typhimurium strain(ΔSt).Owing to the natural hypoxia tropism ofΔSt,Cu_(2)O@ΔSt could selectively colonize hypoxic solid tumors,thus minimizing the adverse effects of the bacteria on normal tis-sues.Upon bacterial metabolism within the tumor,Cu_(2)O@ΔSt generates H_(2)S gas and other acidic substances in the tumor microenvironment(TME),which will in situ trigger the sulfidation of Cu_(2)O to form CuS facilitating tumor-specific photothermal therapy(PTT)under local NIR laser irradiation on the one hand.Meanwhile,the dissolved Cu+ions from Cu_(2)O into the acidified TME enables the nanocatalytic tumor therapy by catalyzing the Fenton-like reaction of decom-posing endogenous H_(2)O_(2) into cytotoxic hydroxyl radicals(·OH)on the other hand.Such a bacterial metabolism-triggered PTT-enhanced nanocatalytic treatment could effectively destroy tumor cells and induce a massive release of tumor antigens and damage-associated molecular patterns,thereby sensitizing tumors to checkpoint blockade(ICB)therapy.The combined nanocatalytic and ICB therapy results in the much-inhibited growth of distant and metastatic tumors,and more importantly,induces a powerful immunological memory effect after the primary tumor ablation.展开更多
Single-atom nanozymes(SAZs)with peroxidase(POD)-like activity have good nanocatalytic tumor therapy(NCT)capabilities.However,insufficient hydrogen peroxide(H2O2)and hydrogen ions in the cells limit their therapeutic e...Single-atom nanozymes(SAZs)with peroxidase(POD)-like activity have good nanocatalytic tumor therapy(NCT)capabilities.However,insufficient hydrogen peroxide(H2O2)and hydrogen ions in the cells limit their therapeutic effects.Herein,to overcome these limitations,a biomimetic single-atom nanozyme system was developed for self-enhanced NCT.We used a previously described approach to produce platelet membrane vesicles.Using a high-temperature carbonization approach,copper SAZs with excellent POD-like activity were successfully synthesized.Finally,through physical extrusion,a proton pump inhibitor(PPI;pantoprazole sodium)and the SAZs were combined with platelet membrane vesicles to create PPS.Both in vivo and in vitro,PPS displayed good tumor-targeting and accumulation abilities.PPIs were able to simultaneously regulate the hydrogen ion,glutathione(GSH),and H2O2 content in tumor cells,significantly improve the catalytic ability of SAZs,and achieve self-enhanced NCT.Our in vivo studies showed that PPS had a tumor suppression rate of>90%.PPS also limited the synthesis of GSH in cells at the source;thus,glutamine metabolism therapy and NCT were integrated into an innovative method,which provides a novel strategy for multimodal tumor therapy.展开更多
Recently,variable nanocatalysts have provided novel,highly selective,mini-mally invasive strategies driven by external physical fields for cancer therapy.In the catalytic reaction,less toxic or nontoxic substances can...Recently,variable nanocatalysts have provided novel,highly selective,mini-mally invasive strategies driven by external physical fields for cancer therapy.In the catalytic reaction,less toxic or nontoxic substances can be in situ converted into toxic agents for cancer suppression.In this review,we systematically summarize the catalytic cancer therapy based on different types of external physical fields,including light,ultrasound,electricity,temperature,X-ray,magnetic field,and microwave.The properties,mechanisms,and advantages of the corresponding external physical fields in cancer therapy are also intro-duced.Importantly,considering the rapid development of catalytic nano-medicine,the research progress of catalytic cancer therapy driven by external physical fields is discussed.Finally,the remaining challenges and outlooks that catalytic cancer therapy faced are also outlined.We believe that the emerging external physical fields-driven nanocatalytic cancer therapy will provide a new avenue for cancer treatment.展开更多
Nanocatalytic medicine triggering in situ catalytic reactions has been considered as a promising strategy for tumor-selective therapeutics.However,the targeted distribution of nanocatalysts was still low,considering t...Nanocatalytic medicine triggering in situ catalytic reactions has been considered as a promising strategy for tumor-selective therapeutics.However,the targeted distribution of nanocatalysts was still low,considering the absence of targeting propulsion capability.Here,encouraged by the fast-developing controllable microrobotics for targeting delivery,a sunflower-like nanocatalytic active swarm(SNCAS)controlled by a three-dimensional(3D)magnetic field was proposed for synergistic tumorselective and magnetic-actively tumor-targeting therapeutics.Furthermore,a patient-derived renal cancer cell 3D organoid was utilized for the verification of the effective tumor therapeutic outcomes.Under the targeted control of 3D magnetic field,the multiple cascade catalytic efficiency of SNCAS based on Fenton reaction was evaluated,resulting in efficient tumor cell apoptosis and death.For the patient-derived organoid treatment,the SNCAS presented significant lethality toward 3D organoid structure to induce cell apoptosis with the collapse of organoid morphology.The targeting efficiency was further enhanced under the magnetic-controllable of SNCAS.Overall,empowered by the magnetic control technology,the synergistic therapeutic strategy based on controllable swarm combined active targeting and tumor-specific catalytic nanomedicine has provided a novel way for advanced cancer therapy.Meanwhile,3D patient-derived organoids were proved as a powerful tool for the effectiveness verification of nanocatalytic medicine.展开更多
The stimuli-responsive anticorrosion coatings have drawn great attention as a prospective corrosion protection approach due to their smart self-repairing properties.In contrast to passive protection mechanism based on...The stimuli-responsive anticorrosion coatings have drawn great attention as a prospective corrosion protection approach due to their smart self-repairing properties.In contrast to passive protection mechanism based on post-corrosion microenvironmental changes,a unique active protection strategy based on nanocatalytic oxygen depletion is proposed in this work to inhibit the occurrence of corrosion.Porous FeeNeC catalysts with outstanding oxygen reduction reaction(ORR)activity(half-wave potential of 0.89 V)is firstly synthesized through pre-coordination with organosilane precursor to obtain homogeneously distributed active sites.When this catalyst is introduced into the coating matrix,uniformly distributed FeeNeC not only compensates the defects but plays a crucial role in adsorption and consumption of diffused oxygen in the coating.Under this dual action,the penetration of corrosive medium,especially oxygen,through coating to metal substrate is greatly suppressed,resulting in effective corrosion inhibition and a significant increase in corrosion resistance of the composite coating compared to pure epoxy coating.This work provides a new perspective and the starting point for the design of high-performance smart coating with active anticorrosion properties.展开更多
Chemodynamic therapy(CDT)based on cascade catalytic nanomedicine has emerged as a promising cancer treatment strategy.However,most of the reported cascade catalytic systems are designed based on symmetric-or co-assemb...Chemodynamic therapy(CDT)based on cascade catalytic nanomedicine has emerged as a promising cancer treatment strategy.However,most of the reported cascade catalytic systems are designed based on symmetric-or co-assembly of multiple catalytic active sites,in which their functions are difficult to perform independently and may interfere with each other.Especially in cascade catalytic system that involves fragile natural-enzymes,the strong oxidation of free-radicals toward natural-enzymes should be carefully considered,and the spatial distribution of the multiple catalytic active sites should be carefully organized to avoid the degradation of the enzyme catalytic activity.Herein,a spatially-asymmetric cascade nanocatalyst is developed for enhanced CDT,which is composed by a Fe_(3)O_(4)head and a closely connected mesoporous silica nanorod immobilized with glucose oxidase(mSiO_(2)-GOx).The mSiO_(2)-GOx subunit could effectively deplete glucose in tumor cells,and meanwhile produce a considerable amount of H_(2)O_(2)for subsequent Fenton reaction under the catalysis of Fe_(3)O_(4)subunit in the tumor microenvironment.Taking the advantage of the spatial isolation of mSiO_(2)-GOx and Fe_(3)O_(4)subunits,the catalysis of GOx and freeradicals generation occur at different domains of the asymmetric nanocomposite,minimizing the strong oxidation of free-radicals toward the activity of GOx at the other side.In addition,direct exposure of Fe_(3)O_(4)subunit without any shelter could further enhance the strong oxidation of free-radicals toward objectives.So,compared with traditional core@shell structure,the long-term stability and efficiency of the asymmetric cascade catalytic for CDT is greatly increased by 138%,thus realizing improved cancer cell killing and tumor restrain efficiency.展开更多
Nanocatalysts mediated reactive oxygen species(ROS)based therapy has been exploited as an alternative therapeutic modality of tumor with high specificity and minimal side effects.However,the treatment outcome is limit...Nanocatalysts mediated reactive oxygen species(ROS)based therapy has been exploited as an alternative therapeutic modality of tumor with high specificity and minimal side effects.However,the treatment outcome is limited by the efficiency of local catalytic reaction.Herein,we report a novel type of core–shell hybrid nanoparticles(CaCO_(3)@MS),consisting of CaCO_(3)and MnSiO_(x),for synergistic tumor inhibition combining enhanced catalytic effect and calcium overload.In this system,MnSiO_(x)serves as catalysts with glutathione(GSH)responsive Mn^(2+)ions release functionality.CaCO_(3)nanoparticles play three important roles,including carbon dioxide(CO_(2))donor,pH modulator,and Ca^(2+)overload agent.It is found that the CaCO_(3)nanoparticles can induce CO_(2)production and pH increase in acidic tumor environment,both of which promote Mn^(2+)mediated ROS generation.And simultaneous release of Ca^(2+)ions from CaCO_(3)triggers calcium overload in tumor,which functions collaboratively with excessive ROS to induce cancer cell apoptosis.The results demonstrate that after treatment with CaCO_(3)@MS,a remarkable tumor inhibition was achieved both in vitro and in vivo,while no clear toxic effect was observed.This study has therefore provided a feasible effective approach to improve catalytic therapeutic efficacy by an“exogenous CO_(2)delivery”strategy for combinational tumor therapy.展开更多
ROS-based tumor therapy based on nanocatalytic medicine has recently been proposed for its tumor-specificity.However,a safe and highly efficient strategy towards getting high enough ROS to kill the hypoxic cancer cell...ROS-based tumor therapy based on nanocatalytic medicine has recently been proposed for its tumor-specificity.However,a safe and highly efficient strategy towards getting high enough ROS to kill the hypoxic cancer cells is still a great challenge.Herein,we report a simple pH/H_()20_(2)-activatable,O_(2)-evolving,and ROS regulating doxorubicin(DOX)and indocyanine green(ICG)co-loading PEGylated polyaniline(PANI)coated CeOx@polyacrylic acid(PAA)nanoclusters for highly selective and optimized cancer combination treatment.It can selectively and greatly enhance intracellular O_(2) and ROS levels in tumor region,which depends on two-step catalytic properties of nanoceria(Ce^(4+)/Ce^(3+)=3.46,neutral surface charge,mostly localize into the cytoplasm,pH 7.4-6.5,catalase-like catalytic agents convert to Ce^(4+)/Ce^(3+)=0.58,negative surface charge,mostly localize into the lysosomes,pH 5-4,oxidase-like catalytic agents,triggered by near infrared(NIA)laser irradiation).Furthermore,the protective effect of polyethylene glycol(PEG),PANI,and PAA ensure that the nanoceria can only play the role of catalase under the irradiation of NIR light arrived at the tumor area.Moreover,loading of nanoceria and ICG onto PANI greatly enhanced photo thermal effect of nanoparticles.(NPs),which is useful for killing cancer cells by relieving hypoxia and promoting cross-membrane drug delivery.to further enhance photodynamic therapy and chemotherapy efficiency.The chemo-photo combination therapies fantastically inhibited tumor growth and prevented tumor recurrence in vivo,suggesting a smart nanotheranostic system to achieve more precise and effective therapies in O_(2)-deprived tumor tissue.展开更多
基金supported by the National Key Research and Development Program of China(Grant No.2022YFB3804500)the National Natural Science Foundation of China(Grant No.52202352,22335006)+4 种基金the Shanghai Municipal Health Commission(Grant No.20224Y0010)the CAMS Innovation Fund for Medical Sciences(Grant No.2021-I2M-5-012)the Basic Research Program of Shanghai Municipal Government(Grant No.21JC1406000)the Fundamental Research Funds for the Central Universities(Grant No.22120230237,2023-3-YB-11,22120220618)the Basic Research Program of Shanghai Municipal Government(23DX1900200).
文摘The current single-atom catalysts(SACs)for medicine still suffer from the limited active site density.Here,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with iron.The constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial effects.Attractively,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading SACs.Consequently,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/C.In addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)depletion.Both in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound healing.This work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.
基金supported by the National Natural Science Foundation of China(52371254,22020102003)the Jilin Province Youth Science and Technology Talent Support Project(QT202229)+1 种基金the Program of Science and Technology Development Plan of Jilin Province of China(YDZJ202302CXJD065)the Natural Science Foundation of Chongqing of China(cstc2021jcyj-msxmX0936)。
文摘Nanocatalytic therapy shows great potential for therapeutic interventions.However,therapeutic efficiency is often limited by unsatisfactory enzyme activity and lack of the coordination of immune system.Therefore,engineering nanozymes activity enhancement while activating immune system will be an effective strategy to achieve efficient tumor therapy.Herein,we synthesize a DSPE-PEG-FA modified manganese dioxide-based dual-atom nanozyme(MDF),on which iridium and platinum atoms are anchored.The obtained MDF can simultaneously mimic four enzyme activities of catalase,oxidase,peroxidase,and glutathione oxidase,set off a reactive oxygen species(ROS)storm,cause tumor cell death.The enzyme activity of MDF can be enhanced by its own photothermal effect.Meanwhile,MDF can consume intracellular glutathione and release Mn^(2+),which can prevent generated ROS from consumption and further activate cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes(cGAS-STING)pathway and promote the secretion of type I interferon,which will help promote dendritic cells maturation,present antigens to T lymphocytes to help kill tumor cells.Ultimately,MDF shows excellent tumor suppressive effects.This work provides a new paradigm for the field of nanozymes and offers a new reference for involvement of cGAS-STING pathway activation in tumor catalytic therapy.
基金Wencheng Wu and Yinying Pu contributed equally to this work.We greatly acknowledge the financial support from CAMS Innovation Fund for Medical Sciences(No.2021-I2M-5-012)National Natural Science Foundation of China(No.21835007)+2 种基金Key Research Program of Frontier Sciences,Chinese Academy of Sciences(No.ZDBS-LY-SLH029)Basic Research Program of Shanghai Municipal Government(No.21JC1406000)China National Postdoctoral Program for Innovative Talents(No.BX20220318).
文摘The low immunogenicity of tumors remains one of the major limitations of cancer immunotherapy.Herein,we report a bacterial metabolisminitiated and photothermal-enhanced nanocatalytic therapy strategy to completely eradicate primary tumor by triggering highly effective antitumor immune responses.Briefly,a microbiotic nanomedicine,designated as Cu_(2)O@ΔSt,has been constructed by conjugating PEGylated Cu_(2)O nanoparticles on the surface of an engineered Salmonella typhimurium strain(ΔSt).Owing to the natural hypoxia tropism ofΔSt,Cu_(2)O@ΔSt could selectively colonize hypoxic solid tumors,thus minimizing the adverse effects of the bacteria on normal tis-sues.Upon bacterial metabolism within the tumor,Cu_(2)O@ΔSt generates H_(2)S gas and other acidic substances in the tumor microenvironment(TME),which will in situ trigger the sulfidation of Cu_(2)O to form CuS facilitating tumor-specific photothermal therapy(PTT)under local NIR laser irradiation on the one hand.Meanwhile,the dissolved Cu+ions from Cu_(2)O into the acidified TME enables the nanocatalytic tumor therapy by catalyzing the Fenton-like reaction of decom-posing endogenous H_(2)O_(2) into cytotoxic hydroxyl radicals(·OH)on the other hand.Such a bacterial metabolism-triggered PTT-enhanced nanocatalytic treatment could effectively destroy tumor cells and induce a massive release of tumor antigens and damage-associated molecular patterns,thereby sensitizing tumors to checkpoint blockade(ICB)therapy.The combined nanocatalytic and ICB therapy results in the much-inhibited growth of distant and metastatic tumors,and more importantly,induces a powerful immunological memory effect after the primary tumor ablation.
基金the Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer(No.2020B121201004)the Guangdong Provincial Major Talents Project(No.2019JC05Y361)+3 种基金the Outstanding Youths Development Scheme of Nanfang Hospital,Southern Medical University(No.2021J008)the Basic and Clinical Cooperative Research and Promotion Program of Anhui Medical University(No.2021xkjT028)the Open Fund of Key Laboratory of Antiinflammatory and Immune Medicine(No.KFJJ-2021-11)Grants for Scientific Research of BSKY from Anhui Medical University(No.1406012201).
文摘Single-atom nanozymes(SAZs)with peroxidase(POD)-like activity have good nanocatalytic tumor therapy(NCT)capabilities.However,insufficient hydrogen peroxide(H2O2)and hydrogen ions in the cells limit their therapeutic effects.Herein,to overcome these limitations,a biomimetic single-atom nanozyme system was developed for self-enhanced NCT.We used a previously described approach to produce platelet membrane vesicles.Using a high-temperature carbonization approach,copper SAZs with excellent POD-like activity were successfully synthesized.Finally,through physical extrusion,a proton pump inhibitor(PPI;pantoprazole sodium)and the SAZs were combined with platelet membrane vesicles to create PPS.Both in vivo and in vitro,PPS displayed good tumor-targeting and accumulation abilities.PPIs were able to simultaneously regulate the hydrogen ion,glutathione(GSH),and H2O2 content in tumor cells,significantly improve the catalytic ability of SAZs,and achieve self-enhanced NCT.Our in vivo studies showed that PPS had a tumor suppression rate of>90%.PPS also limited the synthesis of GSH in cells at the source;thus,glutamine metabolism therapy and NCT were integrated into an innovative method,which provides a novel strategy for multimodal tumor therapy.
基金Fundamental Research Funds for the Central Universities and Research Projects on Biomedical Transformation of China-Japan Friendship Hospital,Grant/Award Number:XK2022-08National Natural Science Foundation of China,Grant/Award Numbers:22061130205,U21A2085+1 种基金National Key Research and Development Program of China,Grant/Award Number:2021YFC2102900Open Foundation of State Key Laboratory of Organic-Inorganic Composites,Beijing University of Chemical Technology,Grant/Award Number:OIC-202201010。
文摘Recently,variable nanocatalysts have provided novel,highly selective,mini-mally invasive strategies driven by external physical fields for cancer therapy.In the catalytic reaction,less toxic or nontoxic substances can be in situ converted into toxic agents for cancer suppression.In this review,we systematically summarize the catalytic cancer therapy based on different types of external physical fields,including light,ultrasound,electricity,temperature,X-ray,magnetic field,and microwave.The properties,mechanisms,and advantages of the corresponding external physical fields in cancer therapy are also intro-duced.Importantly,considering the rapid development of catalytic nano-medicine,the research progress of catalytic cancer therapy driven by external physical fields is discussed.Finally,the remaining challenges and outlooks that catalytic cancer therapy faced are also outlined.We believe that the emerging external physical fields-driven nanocatalytic cancer therapy will provide a new avenue for cancer treatment.
基金This work was supported by the National Key R&D Program of China(No.2018YFA0901700)the National Natural Science Foundation of China(Nos.21878173,52175273,and 82072837)+1 种基金the 111 Project(No.B17026)a grant from the Institute Guo Qiang,Tsinghua University(No.2021GQG1016).
文摘Nanocatalytic medicine triggering in situ catalytic reactions has been considered as a promising strategy for tumor-selective therapeutics.However,the targeted distribution of nanocatalysts was still low,considering the absence of targeting propulsion capability.Here,encouraged by the fast-developing controllable microrobotics for targeting delivery,a sunflower-like nanocatalytic active swarm(SNCAS)controlled by a three-dimensional(3D)magnetic field was proposed for synergistic tumorselective and magnetic-actively tumor-targeting therapeutics.Furthermore,a patient-derived renal cancer cell 3D organoid was utilized for the verification of the effective tumor therapeutic outcomes.Under the targeted control of 3D magnetic field,the multiple cascade catalytic efficiency of SNCAS based on Fenton reaction was evaluated,resulting in efficient tumor cell apoptosis and death.For the patient-derived organoid treatment,the SNCAS presented significant lethality toward 3D organoid structure to induce cell apoptosis with the collapse of organoid morphology.The targeting efficiency was further enhanced under the magnetic-controllable of SNCAS.Overall,empowered by the magnetic control technology,the synergistic therapeutic strategy based on controllable swarm combined active targeting and tumor-specific catalytic nanomedicine has provided a novel way for advanced cancer therapy.Meanwhile,3D patient-derived organoids were proved as a powerful tool for the effectiveness verification of nanocatalytic medicine.
基金financially supported by the“National Natural Science Foundation of China”(52304072)“Funded by Shandong Postdoctora1 Science Foundation”(SDBX2023019)+1 种基金the“Fundamental Research Funds for the Central Universities”(23CX06022A)the“Applied Research Project of Qingdao Postdoctoral Researchers”(QDBSH20230202010).
文摘The stimuli-responsive anticorrosion coatings have drawn great attention as a prospective corrosion protection approach due to their smart self-repairing properties.In contrast to passive protection mechanism based on post-corrosion microenvironmental changes,a unique active protection strategy based on nanocatalytic oxygen depletion is proposed in this work to inhibit the occurrence of corrosion.Porous FeeNeC catalysts with outstanding oxygen reduction reaction(ORR)activity(half-wave potential of 0.89 V)is firstly synthesized through pre-coordination with organosilane precursor to obtain homogeneously distributed active sites.When this catalyst is introduced into the coating matrix,uniformly distributed FeeNeC not only compensates the defects but plays a crucial role in adsorption and consumption of diffused oxygen in the coating.Under this dual action,the penetration of corrosive medium,especially oxygen,through coating to metal substrate is greatly suppressed,resulting in effective corrosion inhibition and a significant increase in corrosion resistance of the composite coating compared to pure epoxy coating.This work provides a new perspective and the starting point for the design of high-performance smart coating with active anticorrosion properties.
基金This work is supported by the National Natural Science Foundation of China(Nos.22075049,21875043,22088101,21701027,21733003,21905052,and 51961145403)the National Key R&D Program of China(Nos.2018YFA0209401 and 2018YFE0201701)+5 种基金Key Basic Research Program of Science and Technology Commission of Shanghai Municipality(No.17JC1400100)Natural Science Foundation of Shanghai(Nos.22ZR1478900,18ZR1404600,and 20490710600)Fundamental Research Funds for the Central Universities(20720220010)Shanghai Rising-Star Program(No.20QA1401200)The authors express their gratitude to Princess Nourah bint Abdulrahman University Researchers Supporting Project number(PNURSP2023R55)Princess Nourah bint Abdulrahman University,Riyadh,Saudi Arabia.The statements made herein are solely the responsibility of the authors。
文摘Chemodynamic therapy(CDT)based on cascade catalytic nanomedicine has emerged as a promising cancer treatment strategy.However,most of the reported cascade catalytic systems are designed based on symmetric-or co-assembly of multiple catalytic active sites,in which their functions are difficult to perform independently and may interfere with each other.Especially in cascade catalytic system that involves fragile natural-enzymes,the strong oxidation of free-radicals toward natural-enzymes should be carefully considered,and the spatial distribution of the multiple catalytic active sites should be carefully organized to avoid the degradation of the enzyme catalytic activity.Herein,a spatially-asymmetric cascade nanocatalyst is developed for enhanced CDT,which is composed by a Fe_(3)O_(4)head and a closely connected mesoporous silica nanorod immobilized with glucose oxidase(mSiO_(2)-GOx).The mSiO_(2)-GOx subunit could effectively deplete glucose in tumor cells,and meanwhile produce a considerable amount of H_(2)O_(2)for subsequent Fenton reaction under the catalysis of Fe_(3)O_(4)subunit in the tumor microenvironment.Taking the advantage of the spatial isolation of mSiO_(2)-GOx and Fe_(3)O_(4)subunits,the catalysis of GOx and freeradicals generation occur at different domains of the asymmetric nanocomposite,minimizing the strong oxidation of free-radicals toward the activity of GOx at the other side.In addition,direct exposure of Fe_(3)O_(4)subunit without any shelter could further enhance the strong oxidation of free-radicals toward objectives.So,compared with traditional core@shell structure,the long-term stability and efficiency of the asymmetric cascade catalytic for CDT is greatly increased by 138%,thus realizing improved cancer cell killing and tumor restrain efficiency.
基金National Natural Science Foundation of China(Nos.52172289 and 51902288)Provincial Key research program of Zhejiang Province(No.2020C04005)Fundamental Research Funds for the Central Universities.
文摘Nanocatalysts mediated reactive oxygen species(ROS)based therapy has been exploited as an alternative therapeutic modality of tumor with high specificity and minimal side effects.However,the treatment outcome is limited by the efficiency of local catalytic reaction.Herein,we report a novel type of core–shell hybrid nanoparticles(CaCO_(3)@MS),consisting of CaCO_(3)and MnSiO_(x),for synergistic tumor inhibition combining enhanced catalytic effect and calcium overload.In this system,MnSiO_(x)serves as catalysts with glutathione(GSH)responsive Mn^(2+)ions release functionality.CaCO_(3)nanoparticles play three important roles,including carbon dioxide(CO_(2))donor,pH modulator,and Ca^(2+)overload agent.It is found that the CaCO_(3)nanoparticles can induce CO_(2)production and pH increase in acidic tumor environment,both of which promote Mn^(2+)mediated ROS generation.And simultaneous release of Ca^(2+)ions from CaCO_(3)triggers calcium overload in tumor,which functions collaboratively with excessive ROS to induce cancer cell apoptosis.The results demonstrate that after treatment with CaCO_(3)@MS,a remarkable tumor inhibition was achieved both in vitro and in vivo,while no clear toxic effect was observed.This study has therefore provided a feasible effective approach to improve catalytic therapeutic efficacy by an“exogenous CO_(2)delivery”strategy for combinational tumor therapy.
基金supported by The National Key Research and Development Program of China(Nos.2018YFF0215500)National Natural Science Foundation of China(Nos.21105047,51773089,and 51973091)+1 种基金the Natural Science Foundation of Jiangsu Province(Nos.BK20181204 and BK20171258)the Science and Technology Items Fund of Nantong City(Applied Basic Research Programs 2017-N,No.MS12017027-2).
文摘ROS-based tumor therapy based on nanocatalytic medicine has recently been proposed for its tumor-specificity.However,a safe and highly efficient strategy towards getting high enough ROS to kill the hypoxic cancer cells is still a great challenge.Herein,we report a simple pH/H_()20_(2)-activatable,O_(2)-evolving,and ROS regulating doxorubicin(DOX)and indocyanine green(ICG)co-loading PEGylated polyaniline(PANI)coated CeOx@polyacrylic acid(PAA)nanoclusters for highly selective and optimized cancer combination treatment.It can selectively and greatly enhance intracellular O_(2) and ROS levels in tumor region,which depends on two-step catalytic properties of nanoceria(Ce^(4+)/Ce^(3+)=3.46,neutral surface charge,mostly localize into the cytoplasm,pH 7.4-6.5,catalase-like catalytic agents convert to Ce^(4+)/Ce^(3+)=0.58,negative surface charge,mostly localize into the lysosomes,pH 5-4,oxidase-like catalytic agents,triggered by near infrared(NIA)laser irradiation).Furthermore,the protective effect of polyethylene glycol(PEG),PANI,and PAA ensure that the nanoceria can only play the role of catalase under the irradiation of NIR light arrived at the tumor area.Moreover,loading of nanoceria and ICG onto PANI greatly enhanced photo thermal effect of nanoparticles.(NPs),which is useful for killing cancer cells by relieving hypoxia and promoting cross-membrane drug delivery.to further enhance photodynamic therapy and chemotherapy efficiency.The chemo-photo combination therapies fantastically inhibited tumor growth and prevented tumor recurrence in vivo,suggesting a smart nanotheranostic system to achieve more precise and effective therapies in O_(2)-deprived tumor tissue.
