In spite of the tumor microenvironments responsive cancer therapy based on Fenton reaction(i.e.,chemodynamic therapy,CDT)has been attracted more attentions in recent years,the limited Fenton reaction efficiency is the...In spite of the tumor microenvironments responsive cancer therapy based on Fenton reaction(i.e.,chemodynamic therapy,CDT)has been attracted more attentions in recent years,the limited Fenton reaction efficiency is the important obstacle to further application in clinic.Herein,we synthesized novel FeO/MoS2 nanocomposites modified by bovine serum albumin(FeO/MoS2-BSA)with boosted Fenton reaction efficiency by the synergistic effect of co-catalyze and photothermal effect of MoS2 nanosheets triggered by the second near-infrared(NIR II)light.In the tumor microenvironments,the MoS2 nanosheets not only can accelerate the conversion of Fe3+ions to Fe2+ions by Mo4+ions on their surface to improve Fenton reaction efficiency,but also endow FeO/MoS2-BSA with good photothermal performances for photothermal-enhanced CDT and photothermal therapy(PTT).Consequently,benefiting from the synergetic-enhanced CDT/PTT,the tumors are eradicated completely in vivo.This work provides innovative synergistic strategy for constructing nanocomposites for highly efficient CDT.展开更多
Glioblastoma(GBM) remains a formidable challenge in oncology.Chemodynamic therapy(CDT) that triggers tumor cell death by reactive oxygen species(ROS) could open up a new door for GBM treatment.Herein,we report a novel...Glioblastoma(GBM) remains a formidable challenge in oncology.Chemodynamic therapy(CDT) that triggers tumor cell death by reactive oxygen species(ROS) could open up a new door for GBM treatment.Herein,we report a novel CDT nanoagent.Hemoglobin(Hb)and glucose oxidase(GOx) were employed as powerful CDT catalysts.Instead of encapsulating the proteins in drug delivery nanocarriers,we formulate multimeric superstructures as self-delivery entities by crosslinking techniques.Red blood cell(RBC) membranes are camouflaged on the protein superstructures to promote the delivery across blood-brain barrier.The as-prepared RBC@Hb@GOx nanoparticles(NPs) offer superior biocompatibility,simplified structure,and high accumulation at the tumor site.We successfully demonstrated that the NPs could efficiently produce toxic ROS to kill U87 MG cancer cells in vitro and inhibit the growth of GBM tumor in vivo,suggesting that the new CDT nanoagent holds great promise for treating GBM.展开更多
Catalysis-based chemodynamic therapy(CDT)is an emerging cancer treatment strategy which uses a Fenton-like reaction to kill tumor cells by catalyzing endogenous hydrogen peroxide(H_(2)O_(2))into a toxic hydroxyl radic...Catalysis-based chemodynamic therapy(CDT)is an emerging cancer treatment strategy which uses a Fenton-like reaction to kill tumor cells by catalyzing endogenous hydrogen peroxide(H_(2)O_(2))into a toxic hydroxyl radical(·OH).The performance of CDT is greatly dependent on PDT agent.Herein,mitochondria-targeting Pt nanoclusters were synthesized using cytochrome c aptamer(CytcApt)as template.The obtained CytcApt-PtNCs can produce.OH by H_(2)O_(2)under the acidic conditions.Moreover,CytcApt-PtNCs could kill 4T1 tumor cells in a pH-dependent manner,but had no side effect on normal 293T cells.Therefore,CytcApt-PtNCs possess excellent therapeutic effect and good biosafety,indicating their great potential for CDT.展开更多
The inadequate quantity of hydrogen peroxide(H_(2)O_(2))in cancer cells promptly results in the constrained success of chemodynamic therapy(CDT).Significant efforts made throughout the years;nevertheless,researchers a...The inadequate quantity of hydrogen peroxide(H_(2)O_(2))in cancer cells promptly results in the constrained success of chemodynamic therapy(CDT).Significant efforts made throughout the years;nevertheless,researchers are still facing the great challenge of designing a CDT agent and securing H_(2)O_(2) supply within the tumor cell.In this study,taking advantage of H_(2)O_(2) level maintenance mechanism in cancer cells,a nanozyme-based bimetallic metal-organic frameworks(MOFs)tandem reactor is fabricated to elevate intracellular H_(2)O_(2) levels,thereby enhancing CDT.In addition,under nearinfrared excitation,the upconversion nanoparticles(UCNPs)loaded into the MOFs can perform photocatalysis and generate hydrogen,which increases cellular susceptibility to radicals induced from H_(2)O_(2),inhibits cancer cell energy,causes DNA damages and induces tumor cell apoptosis,thus improving CDT therapeutic efficacy synergistically.The proposed nanozyme-based bimetallic MOFs-mediated CDT and UCNPs-mediated hydrogen therapy act as combined therapy with high efficacy and low toxicity.展开更多
Chemodynamic therapy(CDT)combined with dual phototherapy(photothermal therapy(PTT)and photodynamic therapy(PDT))is an efficient way to synergistically improve anti-tumor efficacy.However,the combination of multiple mo...Chemodynamic therapy(CDT)combined with dual phototherapy(photothermal therapy(PTT)and photodynamic therapy(PDT))is an efficient way to synergistically improve anti-tumor efficacy.However,the combination of multiple modes often makes the composition of the system more complex,which is not conducive to clinical application.In this study,a dual phototherapy ligand carboxyl-modified Aza-BODIPY(BOD-COOH)and metal active center Cu^(2+)were used to construct multiple-modes metalphotosensitizer nanoparticles(BOD-Cu NPs)via one-step coordination self-assembly for combination therapy of CDT/PDT/PTT.In order to improve delivery efficiency,the targeted hydrophilic molecule pyridinemodified glucose derivative(G-Py)was synthesized and coated onto the BOD-Cu NPs to form a glycosylated nano metal-photosensitizer BOD-Cu@G by electrostatic interaction.The Cu^(2+)in BOD-Cu@G could not only be used as a coordination node for metal-driven self-assembly but also consume intracellular glutathione(GSH),and then catalyze Fenton-like reaction to generate hydroxyl radical(·OH)for CDT.In vitro and in vivo studies revealed that BOD-Cu@G could achieve excellent anti-tumor efficiency by CDTenhanced dual phototherapy.展开更多
Cancer is a leading cause of death worldwide,and a series of strategies has been reported for tumor-specific therapy.Currently,chemodynamic therapy(CDT)has become a research hotspot for antitumor treatment due to its ...Cancer is a leading cause of death worldwide,and a series of strategies has been reported for tumor-specific therapy.Currently,chemodynamic therapy(CDT)has become a research hotspot for antitumor treatment due to its advantages of high specificity,endogenous stimulation,and high biosafety.However,the therapeutic effects of CDT are normally limited in the complex tumor microenvironment(TME),such as insufficient acidity,tumor hypoxia,low hydrogen peroxide(H2O2),and high glutathione(GSH).Consequently,different kinds of multifunctional nanomaterials have been designed to manipulate TME conditions,which provided more opportunities to improve the efficiency of CDT.This review focuses on nanomaterial-based strategies for enhancing CDT through manipulating TME.Upon CDT enhancements,this review would provide a reference for the future development of efficient CDT nanomaterials.展开更多
Dihydroartemisinin(DHA),a first-line antimalarial drug,has demonstrated great anticancer effects in many types of tumors,including liver cancer,glioblastoma,and pancreatic cancer.Due to its abilities to induce program...Dihydroartemisinin(DHA),a first-line antimalarial drug,has demonstrated great anticancer effects in many types of tumors,including liver cancer,glioblastoma,and pancreatic cancer.Due to its abilities to induce programmed cell death(PCD;apoptosis,autophagy and ferroptosis),inhibit tumor metastasis and angiogenesis,and modulate the tumor microenvironment,DHA could become an antineoplastic agent in the foreseeable future.However,the therapeutic efficacy of DHA is compromised owing to its inherent disadvantages,including poor stability,low aqueous solubility,and short plasma halflife.To overcome these drawbacks,nanoscale drug delivery systems(NDDSs),such as polymeric nanoparticles(NPs),liposomes,and metal-organic frameworks(MOFs),have been introduced to maximize the therapeutic efficacy of DHA in either single-drug or multidrug therapy.Based on the beneficial properties of NDDSs,including enhanced stability and solubility of the drug,prolonged circulation time and selective accumulation in tumors,the outcomes of DHA-loaded NDDSs for cancer therapy are significantly improved compared to those of free DHA.This reviewfirst summarizes the current understanding of the anticancer mechanisms of DHA and then provides an overview of DHA-including nanomedicines,aiming to provide inspiration for further application of DHA as an anticancer drug.展开更多
Chemodynamic therapy(CDT),a noninvasive strategy,has emerged as a promising alternative to conventional chemotherapy for treating tumors.However,its therapeutic effect is limited by the amount of H_(2)O_(2),pH value,t...Chemodynamic therapy(CDT),a noninvasive strategy,has emerged as a promising alternative to conventional chemotherapy for treating tumors.However,its therapeutic effect is limited by the amount of H_(2)O_(2),pH value,the hypoxic environment of tumors,and it has suboptimal tumor-targeting ability.In this study,tumor cell membrane-camouflaged mesoporous Fe_(3)O_(4) nanoparticles loaded with perfluoropentane(PFP)and glucose oxidase(GOx)are used as a tumor microenvironment-adaptive nanoplatform(M-mFeP@O_(2)-G),which synergistically enhances the antitumor effect of CDT.Mesoporous Fe_(3)O_(4) nanoparticles are selected as inducers for photothermal and Fenton reactions and as nanocarriers.GOx depletes glucose within tumor cells for starving the cells,while producing H2O2 for subsequent⋅OH generation.Moreover,PFP,which can carry O_(2),relieves hypoxia in tumor cells and provides O_(2) for the cascade reaction.Finally,the nanoparticles are camouflaged with osteosarcoma cell membranes,endowing the nanoparticles with homologous targeting and immune escape abilities.Both in vivo and in vitro evaluations reveal high synergistic therapeutic efficacy of M-mFeP@O_(2)-G,with a desirable tumor-inhibition rate(90.50%),which indicates the great potential of this platform for clinical treating cancer.展开更多
基金This work was supported by the financial aid from the National Natural Science Foundation of China(Grant Nos.51502284,21834007,21521092,21590794,and 21673220)the Program of Science and Technology Development Plan of Jilin Province of China(No.20170101186JC)+1 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB20030300)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2019232).
文摘In spite of the tumor microenvironments responsive cancer therapy based on Fenton reaction(i.e.,chemodynamic therapy,CDT)has been attracted more attentions in recent years,the limited Fenton reaction efficiency is the important obstacle to further application in clinic.Herein,we synthesized novel FeO/MoS2 nanocomposites modified by bovine serum albumin(FeO/MoS2-BSA)with boosted Fenton reaction efficiency by the synergistic effect of co-catalyze and photothermal effect of MoS2 nanosheets triggered by the second near-infrared(NIR II)light.In the tumor microenvironments,the MoS2 nanosheets not only can accelerate the conversion of Fe3+ions to Fe2+ions by Mo4+ions on their surface to improve Fenton reaction efficiency,but also endow FeO/MoS2-BSA with good photothermal performances for photothermal-enhanced CDT and photothermal therapy(PTT).Consequently,benefiting from the synergetic-enhanced CDT/PTT,the tumors are eradicated completely in vivo.This work provides innovative synergistic strategy for constructing nanocomposites for highly efficient CDT.
基金supported by the Villum Fonden, Denmark, Project No. 13153the China Scholarship Council (CSC) for its generous support。
文摘Glioblastoma(GBM) remains a formidable challenge in oncology.Chemodynamic therapy(CDT) that triggers tumor cell death by reactive oxygen species(ROS) could open up a new door for GBM treatment.Herein,we report a novel CDT nanoagent.Hemoglobin(Hb)and glucose oxidase(GOx) were employed as powerful CDT catalysts.Instead of encapsulating the proteins in drug delivery nanocarriers,we formulate multimeric superstructures as self-delivery entities by crosslinking techniques.Red blood cell(RBC) membranes are camouflaged on the protein superstructures to promote the delivery across blood-brain barrier.The as-prepared RBC@Hb@GOx nanoparticles(NPs) offer superior biocompatibility,simplified structure,and high accumulation at the tumor site.We successfully demonstrated that the NPs could efficiently produce toxic ROS to kill U87 MG cancer cells in vitro and inhibit the growth of GBM tumor in vivo,suggesting that the new CDT nanoagent holds great promise for treating GBM.
基金This work is supported by the Cross Research Fund of Biomedical Engineering of Shanghai Jiao Tong University(YG2019QNA43).
文摘Catalysis-based chemodynamic therapy(CDT)is an emerging cancer treatment strategy which uses a Fenton-like reaction to kill tumor cells by catalyzing endogenous hydrogen peroxide(H_(2)O_(2))into a toxic hydroxyl radical(·OH).The performance of CDT is greatly dependent on PDT agent.Herein,mitochondria-targeting Pt nanoclusters were synthesized using cytochrome c aptamer(CytcApt)as template.The obtained CytcApt-PtNCs can produce.OH by H_(2)O_(2)under the acidic conditions.Moreover,CytcApt-PtNCs could kill 4T1 tumor cells in a pH-dependent manner,but had no side effect on normal 293T cells.Therefore,CytcApt-PtNCs possess excellent therapeutic effect and good biosafety,indicating their great potential for CDT.
基金funded by the National Natural Science Foundation of China(NSFC 81971734,32071323,32271410)the Science and Technology Projects in Fujian Province(2022FX1,2023Y4008)the Open Research Fund of Academy of Advanced Carbon Conversion Technology,Huaqiao University(AACCT0004).
文摘The inadequate quantity of hydrogen peroxide(H_(2)O_(2))in cancer cells promptly results in the constrained success of chemodynamic therapy(CDT).Significant efforts made throughout the years;nevertheless,researchers are still facing the great challenge of designing a CDT agent and securing H_(2)O_(2) supply within the tumor cell.In this study,taking advantage of H_(2)O_(2) level maintenance mechanism in cancer cells,a nanozyme-based bimetallic metal-organic frameworks(MOFs)tandem reactor is fabricated to elevate intracellular H_(2)O_(2) levels,thereby enhancing CDT.In addition,under nearinfrared excitation,the upconversion nanoparticles(UCNPs)loaded into the MOFs can perform photocatalysis and generate hydrogen,which increases cellular susceptibility to radicals induced from H_(2)O_(2),inhibits cancer cell energy,causes DNA damages and induces tumor cell apoptosis,thus improving CDT therapeutic efficacy synergistically.The proposed nanozyme-based bimetallic MOFs-mediated CDT and UCNPs-mediated hydrogen therapy act as combined therapy with high efficacy and low toxicity.
基金supported by the National Natural Science Foundation of China(No.22171230)the Project of Science and Technology of Social Development in Shaanxi Province(No.2023YBSF-151)。
文摘Chemodynamic therapy(CDT)combined with dual phototherapy(photothermal therapy(PTT)and photodynamic therapy(PDT))is an efficient way to synergistically improve anti-tumor efficacy.However,the combination of multiple modes often makes the composition of the system more complex,which is not conducive to clinical application.In this study,a dual phototherapy ligand carboxyl-modified Aza-BODIPY(BOD-COOH)and metal active center Cu^(2+)were used to construct multiple-modes metalphotosensitizer nanoparticles(BOD-Cu NPs)via one-step coordination self-assembly for combination therapy of CDT/PDT/PTT.In order to improve delivery efficiency,the targeted hydrophilic molecule pyridinemodified glucose derivative(G-Py)was synthesized and coated onto the BOD-Cu NPs to form a glycosylated nano metal-photosensitizer BOD-Cu@G by electrostatic interaction.The Cu^(2+)in BOD-Cu@G could not only be used as a coordination node for metal-driven self-assembly but also consume intracellular glutathione(GSH),and then catalyze Fenton-like reaction to generate hydroxyl radical(·OH)for CDT.In vitro and in vivo studies revealed that BOD-Cu@G could achieve excellent anti-tumor efficiency by CDTenhanced dual phototherapy.
基金supported by the National Natural Science Foundation of China(Nos.22274012,21974010)the Fundamental Research Funds for the Central Universities,China(No.2233300007)the Key Project of Science and Technology Plan of Beijing Education Commission,China(No.KZ20231002807).
文摘Cancer is a leading cause of death worldwide,and a series of strategies has been reported for tumor-specific therapy.Currently,chemodynamic therapy(CDT)has become a research hotspot for antitumor treatment due to its advantages of high specificity,endogenous stimulation,and high biosafety.However,the therapeutic effects of CDT are normally limited in the complex tumor microenvironment(TME),such as insufficient acidity,tumor hypoxia,low hydrogen peroxide(H2O2),and high glutathione(GSH).Consequently,different kinds of multifunctional nanomaterials have been designed to manipulate TME conditions,which provided more opportunities to improve the efficiency of CDT.This review focuses on nanomaterial-based strategies for enhancing CDT through manipulating TME.Upon CDT enhancements,this review would provide a reference for the future development of efficient CDT nanomaterials.
基金supported by the National Natural Science Foundation of China[51922111]the Science and Technology Development Fund,Macao SAR[File no.0124/2019/A3]Guangdong-Hong Kong-Macao Joint Laboratory of Optoelectronic and Magnetic Functional Materials[2019B121205002].
文摘Dihydroartemisinin(DHA),a first-line antimalarial drug,has demonstrated great anticancer effects in many types of tumors,including liver cancer,glioblastoma,and pancreatic cancer.Due to its abilities to induce programmed cell death(PCD;apoptosis,autophagy and ferroptosis),inhibit tumor metastasis and angiogenesis,and modulate the tumor microenvironment,DHA could become an antineoplastic agent in the foreseeable future.However,the therapeutic efficacy of DHA is compromised owing to its inherent disadvantages,including poor stability,low aqueous solubility,and short plasma halflife.To overcome these drawbacks,nanoscale drug delivery systems(NDDSs),such as polymeric nanoparticles(NPs),liposomes,and metal-organic frameworks(MOFs),have been introduced to maximize the therapeutic efficacy of DHA in either single-drug or multidrug therapy.Based on the beneficial properties of NDDSs,including enhanced stability and solubility of the drug,prolonged circulation time and selective accumulation in tumors,the outcomes of DHA-loaded NDDSs for cancer therapy are significantly improved compared to those of free DHA.This reviewfirst summarizes the current understanding of the anticancer mechanisms of DHA and then provides an overview of DHA-including nanomedicines,aiming to provide inspiration for further application of DHA as an anticancer drug.
基金The authors thank the financial support from National Natural Science Foundation of China(51925304,52173140 and 51803173)Sichuan Science and Technology Program(2021YJ0192)the Opening Project of State Key Laboratory of Polymer Materials Engineering(Sichuan University)(Grant No.sklpme2020-4-13).
文摘Chemodynamic therapy(CDT),a noninvasive strategy,has emerged as a promising alternative to conventional chemotherapy for treating tumors.However,its therapeutic effect is limited by the amount of H_(2)O_(2),pH value,the hypoxic environment of tumors,and it has suboptimal tumor-targeting ability.In this study,tumor cell membrane-camouflaged mesoporous Fe_(3)O_(4) nanoparticles loaded with perfluoropentane(PFP)and glucose oxidase(GOx)are used as a tumor microenvironment-adaptive nanoplatform(M-mFeP@O_(2)-G),which synergistically enhances the antitumor effect of CDT.Mesoporous Fe_(3)O_(4) nanoparticles are selected as inducers for photothermal and Fenton reactions and as nanocarriers.GOx depletes glucose within tumor cells for starving the cells,while producing H2O2 for subsequent⋅OH generation.Moreover,PFP,which can carry O_(2),relieves hypoxia in tumor cells and provides O_(2) for the cascade reaction.Finally,the nanoparticles are camouflaged with osteosarcoma cell membranes,endowing the nanoparticles with homologous targeting and immune escape abilities.Both in vivo and in vitro evaluations reveal high synergistic therapeutic efficacy of M-mFeP@O_(2)-G,with a desirable tumor-inhibition rate(90.50%),which indicates the great potential of this platform for clinical treating cancer.
