Lactic acid(LA)plays a major role in the occurrence,development,and spread of cancer.Enlightened by its high accumulation in tumor site,a novel lactate oxidase(LOD)conjugated two-dimensional Pd@Ir nanoplatform(Pd@Ir-L...Lactic acid(LA)plays a major role in the occurrence,development,and spread of cancer.Enlightened by its high accumulation in tumor site,a novel lactate oxidase(LOD)conjugated two-dimensional Pd@Ir nanoplatform(Pd@Ir-LOD,PIL)was fabricated to combine cascade reaction with photothermal for tumor therapy.In detail,the overexpressed LA in tumor microenvironment(TME)was a key factor to activate the PIL-based cascade reaction:(1)Plenty of H_(2)O_(2)could be generated from LA by the catalysis of LOD with O_(2);(2)potent·OH was produced from H_(2)O_(2)due to the peroxidase(POD)-like activity of PIL;(3)meantime,PIL’s catalase(CAT)-like activity could decompose part H_(2)O_(2)into O_(2)to achieve the purpose of LA cyclic oxidization.Moreover,the reduced glutathione(GSH)scavenging capability of PIL might protect the produced reactive oxygen species(ROS)from being cleared to further improve the cascade therapeutic effect.More importantly,PIL had excellent photothermal conversion efficiency(37.35%)and manifested a surprising temperature rising effect in tumor.Taken together,the decreasing LA concentration,accumulation of high-toxic ROS,the depletion of GSH together with the higher intra-tumoral temperature potently enhanced in vivo antitumor therapy.Therefore,a promising therapeutic tactic based on PIL integrating endogenous LA consumption,chemodynamic therapy(CDT),and photothermal therapy(PTT)has been put forward.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
Osteosarcoma is usually resistant to immunotherapy and,thus primarily relies on surgical resection and high-dosage chemotherapy.Unfortunately,less invasive or toxic therapies such as photothermal therapy(PTT)and chemo...Osteosarcoma is usually resistant to immunotherapy and,thus primarily relies on surgical resection and high-dosage chemotherapy.Unfortunately,less invasive or toxic therapies such as photothermal therapy(PTT)and chemodynamic therapy(CDT)generally failed to show satisfactory outcomes.Adequate multimodal therapies with proper safety profiles may provide better solutions for osteosarcoma.Herein,a simple nanocomposite that synergistically combines CDT,PTT,and chemotherapy for osteosarcoma treatment was fabricated.In this composite,small 2D Ni Fe-LDH flakes were processed into 3D hollow nanospheres via template methods to encapsulate 5-Fluorouracil(5-FU)with high loading capacity.The nanospheres were then adsorbed onto larger 2D Ti3C2MXene monolayers and finally shielded by bovine serum albumin(BSA)to form 5-FU@Ni Fe-LDH/Ti3C2/BSA nanoplatforms(5NiTiB).Both in vitro and in vivo data demonstrated that the 5-FU induced chemotherapy,Ni Fe-LDH driven chemodynamic effects,and MXene-based photothermal killing collectively exhibited a synergistic“all-in-one”anti-tumor effect.5NiTiB improved tumor suppression rate from<5%by 5-FU alone to~80.1%.This nanotherapeutic platform achieved higher therapeutic efficacy with a lower agent dose,thereby minimizing side effects.Moreover,the composite is simple to produce,enabling the fine-tuning of dosages to suit different requirements.Thus,the platform is versatile and efficient,with potential for further development.展开更多
Recently,the development of chemodynamic therapy(CDT)offers a potential approach for fighting bacteria and treating infectious diseases,in which those CDT nanoagents can catalyze the generation of hydroxyl radicals(&#...Recently,the development of chemodynamic therapy(CDT)offers a potential approach for fighting bacteria and treating infectious diseases,in which those CDT nanoagents can catalyze the generation of hydroxyl radicals(·OH)to destroy bacteria.In this work,to improve the efficiency of CDT,we have designed a new kind of metformin(Met)-capped two-dimensional Cu_(2)(OH)_(3)Cl nanosheets(CuOHCl-Met NSs)with good monodispersity,highly positive charge,and good biocompatibility for improving antibacterial effect and accelerating wound healing.With the capped Met,CuOHCl-Met NSs can effectively kill bacteria under a low concentration(6μg·mL^(−1))and a short treatment time(in 15 min),showing great advantages over the counterpart without Met.In vivo results demonstrated that CuOHCl-Met NSs accelerated the tissue regeneration of staphylococcus aureus-infected dermal wounds.This study provides a new pathway for improving efficiency of CDT nanoagent through using old drug.展开更多
Due to the hypoxic state of the tumor microenvironment(TME),photodynamic therapy(PDT)suffers from insufficient ROS production.The metal-polyphenol network-mediated Fenton reaction can generate reac-tive oxygen species...Due to the hypoxic state of the tumor microenvironment(TME),photodynamic therapy(PDT)suffers from insufficient ROS production.The metal-polyphenol network-mediated Fenton reaction can generate reac-tive oxygen species(ROS)by consuming H_(2)O_(2) in TME,improving the inadequate ROS generation problem of PDT.Therefore,synergistic therapy combining PDT and Fenton response-based CDT is a promising ap-proach for cancer treatment.Herein,a metal-polyphenol nanocomposite was deposited with gallic acid grafted hyaluronic acid and Fe^(3+) to contrast a Ce6 nano-delivery system(Ce6@HSF NPs)for melanoma synergistic therapy.Ce6@HSF NPs could be used as a Fenton reagent to induce the·OH production and enhance the PDT effect of Ce6 to a certain extent.After 4 h of cellular uptake,the fluorescence intensity of Ce6 in the Ce6@HSF NPs group was higher than 3 times that in the Ce6 group.The intracellular ROS generation level of the Ce6@HSF NPs(L)group combining CDT and PDT was higher than that of the Ce6 group and Ce6@HSF NPs group.In vitro and in vivo anti-melanoma studies show that Ce6@HSF NPs(L)group exhibited better anti-melanoma than other groups.Together,Ce6@HSF NPs provide a promising synergistic treatment potential for melanoma.展开更多
Osteosarcoma is a refractory bone disease in young people that needs the updating and development of effective treatment.Although nanotechnology is widely applied in cancer therapy,poor targeting and inadequate effi-c...Osteosarcoma is a refractory bone disease in young people that needs the updating and development of effective treatment.Although nanotechnology is widely applied in cancer therapy,poor targeting and inadequate effi-ciency hinder its development.In this study,we prepared alendronate(ALD)/K7M2 cell membranes-coated hollow manganese dioxide(HMnO_(2))nanoparticles as a nanocarrier to load Ginsenoside Rh2(Rh2)for Mag-netic Resonance imaging(MRI)-guided immuno-chemodynamic combination osteosarcoma therapy.Subse-quently,the ALD and K7M2 cell membranes were successively modified on the surface of HMnO_(2) and loaded with Rh2.The tumor microenvironment(TME)-activated Rh2@HMnO_(2)-AM nanoparticles have good bone tumor-targeting and tumor-homing capabilities,excellent GSH-sensitive drug release profile and MRI capability,and attractive immuno-chemodynamic combined therapeutic efficiency.The Rh2@HMnO_(2)-AM nanoparticles can effectively trigger immunogenic cell death(ICD),activate CD4^(+)/CD8^(+)T cells in vivo,and upregulate BAX,BCL-2 and Caspase-3 in cellular level.Further results revealed that Rh2@HMnO_(2)-AM enhanced the secretion of IL-6,IFN-γand TNF-αin serum and inhibited the generation of FOXP3^(+)T cells(Tregs)in tumors.Moreover,the Rh2@HMnO_(2)-AM treatment significant restricted tumor growth in-situ tumor-bearing mice.Therefore,Rh2@HMnO_(2)-AM may serve as an effective and bio-friendly nanoparticle platform combined with immuno-therapy and chemodynamic therapy to provide a novel approach to osteosarcoma therapy.展开更多
Combining photodynamic therapy(PDT)with chemodynamic therapy(CDT)has been proven to be a promising strategy to improve the treatment efficiency of cancer,because of the synergistic therapeutic effect arising between t...Combining photodynamic therapy(PDT)with chemodynamic therapy(CDT)has been proven to be a promising strategy to improve the treatment efficiency of cancer,because of the synergistic therapeutic effect arising between the two modalities.Herein,we report an inorganic nanoagent based on ternary NiCoTi-layered double hydroxide(NiCoTi-LDH)nanosheets to realize highly efficient photodynamic/chemodynamic synergistic therapy.The NiCoTi-LDH nanosheets exhibit oxygen vacancy-promoted electron-hole separation and photogenerated holeinduced O_(2)-independent reactive oxygen species(ROS)generation under acidic circumstances,realizing in situ pH-responsive PDT.Moreover,due to the effective conversion between Co^(3+)and Co^(2+)caused by photogenerated electrons,the NiCoTi-LDH nanosheets catalyze the release of hydroxyl radicals(-OH)from H_(2)O_(2)through Fenton reactions,resulting in CDT.Laser irradiation enhances the catalyzed ability of the NiCoTi-LDH nanosheets to promote the ROS generation,resulting in a better performance than TiO_(2)nanoparticles at pH 6.5.In vitro and in vivo experimental results show conclusively that NiCoTi-LDH nanosheets plus irradiation lead to efficient cell apoptosis and significant inhibition of tumor growth.This study reports a new pH-responsive inorganic nanoagent with oxygen vacancy-promoted photodynamic/chemodynamic synergistic performance,offering a potentially appealing clinical strategy for selective tumor elimination.展开更多
Radiotherapy(RT) can potentially induce systemic immune responses by initiating immunogenic cell death(ICD) of tumor cells.However,RT-induced antitumor immunologic responses are sporadic and insufficient against cance...Radiotherapy(RT) can potentially induce systemic immune responses by initiating immunogenic cell death(ICD) of tumor cells.However,RT-induced antitumor immunologic responses are sporadic and insufficient against cancer metastases.Herein,we construct multifunctional self-sufficient nanoparticles(MARS) with dual-enzyme activity(GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic relapse.In addition to limiting the Warburg effect to actualize starvation therapy,MARS catalyzes glucose to produce hydrogen peroxide(H_(2)O_(2)),which is then used in the Cu^(+)-mediated Fenton-like reaction and RT sensitization.RT and chemodynamic therapy produce reactive oxygen species in the form of radical storms,which have a robust ICD impact on mobilizing the immune system.Thus,when MARS is combined with RT,potent systemic antitumor immunity can be generated by activating antigen-presenting cells,promoting dendritic cells maturation,increasing the infiltration of cytotoxic T lymphocytes,and reprogramming the immuno suppre ssive tumor microenvironment.Furthermore,the synergistic therapy of RT and MARS effectively suppresses local tumor growth,increases mouse longevity,and results in a 90% reduction in lung metastasis and postoperative recurrence.Overall,we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.展开更多
Malignant tumors are the main diseases threatening human life. Using precise theranostics to diagnose and cure tumors has emerged as a new method to improve patient survival. Based on the current development of precis...Malignant tumors are the main diseases threatening human life. Using precise theranostics to diagnose and cure tumors has emerged as a new method to improve patient survival. Based on the current development of precise tumor imaging, image-guided tumor therapy has received widespread attention because it is beneficial for developing precise treatment of tumors, has the potential to improve the efficacy of tumor therapy and reduce the incidence of adverse side effects. Nanoprobes, which are nanomaterial functionalized with specific biomolecules, have intrigued intense interest due to their great potential in monitoring biorecognition and biodetection evens. Benefiting from the unique advantages of nanomaterials, including the easy surface functionalization, the unique imaging performances, and the high drug loading capacity, nanoprobes have become a powerful tool to simultaneously realize tumor precise imaging, diagnosis, and therapy. This review introduces the non-invasive tumor precise imaging and highlights the recent advances of image-guided oncotherapy mediated by nanoprobes in anti-tumor drug delivery, tumor precise surgical navigation, chemodynamic therapy, and phototherapy. Finally, a perspective on the challenge and future direction of nanoprobes in imaging-guided tumor theranostics is also discussed.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
The realization of real-time thermal feedback for monitoring photothermal therapy(PTT)under near-infrared(NIR)light irradiation is of great interest and challenge for antitumor therapy.Herein,by assembling highly effi...The realization of real-time thermal feedback for monitoring photothermal therapy(PTT)under near-infrared(NIR)light irradiation is of great interest and challenge for antitumor therapy.Herein,by assembling highly efficient photothermal conversion gold nanorods and a temperature-responsive probe((E)-4-(4-(diethylamino)styryl)-1-methylpyridin-1-ium,PyS)within MOF-199,an intelligent nanoplatform(AMPP)was fabricated for simultaneous chemodynamic therapy and NIR light-induced temperature-feedback PTT.The fluorescence intensity and temperature of the PyS probe are linearly related due to the restriction of the rotation of the characteristic monomethine bridge.Moreover,the copper ions resulting from the degradation of MOF-199 in an acidic microenvironment can convert H_(2)O_(2)into•OH,resulting in tumor ablation through a Fenton-like reaction,and this process can be accelerated by increasing the temperature.This study establishes a feasible platform for fabricating highly sensitive temperature sensors for efficient temperature-feedback PTT.展开更多
Chemodynamic therapy(CDT),an inventive approach to cancer treatment,exploits innate chemical processes to trigger cell death through the generation of reactive oxygen species(ROS).While offering advantages over conven...Chemodynamic therapy(CDT),an inventive approach to cancer treatment,exploits innate chemical processes to trigger cell death through the generation of reactive oxygen species(ROS).While offering advantages over conventional treatments,the optimization of CDT efficacy presents challenges stemming from suboptimal catalytic efficiency and the counteractive ROS scavenging effect of intracellular glutathione(GSH).In this study,we aim to address this dual challenge by delving into the role of copper valence states in CDT.Leveraging the unique attributes of copper-based nanoparticles,especially zero-valent copper nanoparticles(CuPd NPs),we aim to enhance the therapeutic potential of CDT.Our experiments reveal that zero-valent CuPd NPs outperform divalent copper nanoparticles(Ox-CuPd NPs)by displaying superior catalytic performance and sustaining ROS generation through a dual approach integrating peroxidase-like(POD-like)activity and Cu+release.Notably,zero-valent NPs exhibit enhanced GSH depletion compared to their divalent counterparts,thereby intensifying CDT and inducing ferroptosis,ultimately resulting in high-efficiency tumor growth inhibition.These findings reveal the impact of valences on CDT,providing novel insights for the optimization and design of CDT agents.展开更多
Osteosarcoma(OS)is a malignant tumor with a high rate of recurrence.Recently,biodegradable Mg-based implants have become a new therapeutic platform for bone-related diseases.However,poor biosafety and deficient intell...Osteosarcoma(OS)is a malignant tumor with a high rate of recurrence.Recently,biodegradable Mg-based implants have become a new therapeutic platform for bone-related diseases.However,poor biosafety and deficient intelligent tumor-killing ability of Mg-based implants are still the main challenges for the pre-cise treatment of OS.Herein,based on the excellent catalytic and photothermal conversion properties of nanozyme ferric oxide(Fe_(3)O_(4)),a novel two-step hydrothermal method for in situ preparation of Fe_(3)O_(4)nanosheets on the surface of plasma electrolytic oxidation(PEO)-treated Mg alloy using Mg-Fe layered double hydroxides(Mg-Fe LDH)as precursor was proposed.Compared with Mg alloy,there were no obvious corrosion cracks on the surface of Fe_(3)O_(4)nanosheets-coated Mg alloy(Fe_(3)O_(4)-NS)immersed in 0.9 wt.%NaCl for 14 days,which demonstrated the corrosion resistance of Mg alloy was significantly enhanced.Cytocompatibility experiments and hemolysis assay confirmed the great biocompatibility of Fe_(3)O_(4)-NS,especially,hemolysis ratio was lower than 1%.Meanwhile,Fe_(3)O_(4)-NS presented excellent cat-alytic oxidation capacity in the presence of H_(2)O_(2),and its temperature can significantly increase from 27℃to approximately 56℃under NIR irradiation.Therefore,intelligent responsive Fe_(3)O_(4)nanosheets-engineered Mg-based implants demonstrated excellent antitumor properties in vivo and in vitro due to their photothermal and chemodynamic synergetic effects.This study provides a novel approach for the preparation of Fe_(3)O_(4)coatings on the surface of Mg alloys and a new strategy for the treatment of OS.展开更多
Cu_(2-x)S nanostructures have been intensively studied as outstanding chemodynamic therapy(CDT)and good photothermal therapy(PTT)antibacterial agents due to their highly efficient Cu(Ⅰ)-initiated Fenton-like catalyti...Cu_(2-x)S nanostructures have been intensively studied as outstanding chemodynamic therapy(CDT)and good photothermal therapy(PTT)antibacterial agents due to their highly efficient Cu(Ⅰ)-initiated Fenton-like catalytic activity and good photothermal conversion property.However,they still suffer from shortage of Cu(Ⅰ)supply in the long-term and comparatively low inherent photothermal conversion efficiency.Herein,we constructed a self-enhanced synergistic PTT/CDT nanoplatform(Cu_(1.94)S@MPN)by coating Cu_(1.94)S nanoparticles with Fe(Ⅲ)/tannic acid based metal-polyphenol networks(MPN).Activated by the acidic bacterial infection microenvironment,Cu_(1.94)S@MPN could be decomposed to continuously release Cu(Ⅱ),Fe(Ⅲ)ions and tannic acid.As the result of tannic acid-involved Cu and Fe redox cycling,Cu(Ⅰ)/Fe(Ⅱ)-rich CDT could be achieved through the highly accelerated catalytic Fenton/Fenton-like reactions.More importantly,experimental results demonstrated that Cu_(1.94)S@MPN exhibited both excellent photothermal antibacterial and photothermal-enhanced CDT properties to eradicate bacteria in vitro and in vivo.Overall,this novel nanotherapeutics has great potential to become a clinic candidate for anti-infective therapy in future.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
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
Diabetic patients often have problems such as residual tumor and wound infection after tumor resection,causing severe clinical problems.It is urgent to develop effective therapies to reach oncotherapy/antiinfection/pr...Diabetic patients often have problems such as residual tumor and wound infection after tumor resection,causing severe clinical problems.It is urgent to develop effective therapies to reach oncotherapy/antiinfection/promotion of wound healing combined treatment.Herein,we propose CS/MnO_(2)-GO_x (CMGO_x)nanocatalysts for the specific catalytic generation of ~·OH to inhibit tumors and bacteria in a hyperglycemic environment.The good biocompatible chitosan (CS),as a carrier for the catalyst,exhibits excellent antibacterial effect as well as promotes wound healing.Glucose oxidase (GO_x) is loaded on the surface of CS nanoparticles to generate H_(2)O_(2) and gluconic acid by consuming glucose (starvation therapy,ST) and O_(2).The MnO_(2) depletes glutathione (GSH) to produce Mn^(2+),amplifying oxidative stress and further promoting the activity of Mn^(2+)-mediated Fenton-like reaction to produce~·OH (chemodynamic therapy,CDT)in weak acidic environment.Moreover,the produced gluconic acid lowers the p H of the environment,enhancing chemodynamic therapy (ECDT).The tumor cells and bacteria are efficiently eliminated by the synergistic effect of ST and ECDT.The MnO_(2) nanoparticles at neutral environment decomposes H_(2)O_(2) into O_(2),which cooperate with CS to promote healing.The self-enhanced cascade reaction of CMGO_x in situ exhibits excellent effects of antitumor/antibacterial therapy and promotion of wound healing,offering a promising integrated treatment for diabetic patients after tumor surgical resection.展开更多
Inspired by the limitations of nanoparticles in cancer treatment caused by their low therapeutic effects and biotoxicity,biocompatible and photothermal enhanced copper oxide-decorated carbon nanospheres(CuO@CNSs)with ...Inspired by the limitations of nanoparticles in cancer treatment caused by their low therapeutic effects and biotoxicity,biocompatible and photothermal enhanced copper oxide-decorated carbon nanospheres(CuO@CNSs)with doxorubicin hydrochloride(DOX)loading were constructed.CNSs as photothermal agents were synthesized by a hydrothermal reaction.CuO was adsorbed on the surface of CNSs,which improved the photothermal conversion efficiency due to the electron transitions between C-2 p and Cu-3 d.In addition,CuO would release Cu2+ions in the tumor microenvironment,which could produce hydroxyl radical(·OH)to induce cancer cells apoptosis via Haber-Weiss and Fenton-like reactions.DOX as a chemotherapeutic agent was located on the surface of CuO@CNSs by electrostatic adsorption and released quickly in the tumor microenvironment to kill cancer cells.The CuO@CNSs-DOX nanoplatforms realized the combination therapy of photothermal therapy(PTT),chemodynamic therapy(CDT),and chemotherapy(CT),which have strong potential for cancer treatment.展开更多
Cu-mediated chemodynamic therapy(CDT)has attracted prominent attention owing to its advantages of pH independence and high efficiency comparing to Fe-mediated CDT,while the application of Cu-based CDT agents was imped...Cu-mediated chemodynamic therapy(CDT)has attracted prominent attention owing to its advantages of pH independence and high efficiency comparing to Fe-mediated CDT,while the application of Cu-based CDT agents was impeded due to the high copper consumption caused by the metabolism loss of copper and the resultant potential toxicity.Herein,we developed a new copper-mediated CDT agent with extremely low Cu usage by anchoring copper on cross-linked lipoic acid nanoparticles(Cu@cLAs).After endocytosis into tumor cells,the Cu@cLAs were dissociated into LA and dihydrolipoic acid(DHLA)(reduced form of LA)and released Cu^(2+)and Cu+(oxidized form of Cu^(2+)),the two redox couples recycled each other in cells to achieve the efficient killing of cancer cells by delaying metabolic loss and increasing the ROS level of tumor cells.The self-recycling was confirmed in cells by the sustained high Cu/DHLA content and persistent ROS generation process.The antitumor study based on the MCF-7/R nude mice gave the Cu@cLAs a tumor inhibitory rate up to 77.9%at the copper of 0.05 mg kg^(−1),the first dosage reported so far lower than that of normal serum copper(0.83±0.21 mg kg^(−1)).This work provides not only a new promising clinical strategy for the copper excessive use in copper-mediated CDT,but also gives a clue for other metal mediated disease therapies with the high metal consumption.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
基金supported by the National Natural Science Foundation of China(No.22075233)Natural Science Foundation of Fujian Province(No.2022J01023).
文摘Lactic acid(LA)plays a major role in the occurrence,development,and spread of cancer.Enlightened by its high accumulation in tumor site,a novel lactate oxidase(LOD)conjugated two-dimensional Pd@Ir nanoplatform(Pd@Ir-LOD,PIL)was fabricated to combine cascade reaction with photothermal for tumor therapy.In detail,the overexpressed LA in tumor microenvironment(TME)was a key factor to activate the PIL-based cascade reaction:(1)Plenty of H_(2)O_(2)could be generated from LA by the catalysis of LOD with O_(2);(2)potent·OH was produced from H_(2)O_(2)due to the peroxidase(POD)-like activity of PIL;(3)meantime,PIL’s catalase(CAT)-like activity could decompose part H_(2)O_(2)into O_(2)to achieve the purpose of LA cyclic oxidization.Moreover,the reduced glutathione(GSH)scavenging capability of PIL might protect the produced reactive oxygen species(ROS)from being cleared to further improve the cascade therapeutic effect.More importantly,PIL had excellent photothermal conversion efficiency(37.35%)and manifested a surprising temperature rising effect in tumor.Taken together,the decreasing LA concentration,accumulation of high-toxic ROS,the depletion of GSH together with the higher intra-tumoral temperature potently enhanced in vivo antitumor therapy.Therefore,a promising therapeutic tactic based on PIL integrating endogenous LA consumption,chemodynamic therapy(CDT),and photothermal therapy(PTT)has been put forward.
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 Science Fund for Excellent Young Scholars(No.82022070,China)National Natural Science Foundation of China(NSFC)General Program(No.81872824,China)。
文摘Osteosarcoma is usually resistant to immunotherapy and,thus primarily relies on surgical resection and high-dosage chemotherapy.Unfortunately,less invasive or toxic therapies such as photothermal therapy(PTT)and chemodynamic therapy(CDT)generally failed to show satisfactory outcomes.Adequate multimodal therapies with proper safety profiles may provide better solutions for osteosarcoma.Herein,a simple nanocomposite that synergistically combines CDT,PTT,and chemotherapy for osteosarcoma treatment was fabricated.In this composite,small 2D Ni Fe-LDH flakes were processed into 3D hollow nanospheres via template methods to encapsulate 5-Fluorouracil(5-FU)with high loading capacity.The nanospheres were then adsorbed onto larger 2D Ti3C2MXene monolayers and finally shielded by bovine serum albumin(BSA)to form 5-FU@Ni Fe-LDH/Ti3C2/BSA nanoplatforms(5NiTiB).Both in vitro and in vivo data demonstrated that the 5-FU induced chemotherapy,Ni Fe-LDH driven chemodynamic effects,and MXene-based photothermal killing collectively exhibited a synergistic“all-in-one”anti-tumor effect.5NiTiB improved tumor suppression rate from<5%by 5-FU alone to~80.1%.This nanotherapeutic platform achieved higher therapeutic efficacy with a lower agent dose,thereby minimizing side effects.Moreover,the composite is simple to produce,enabling the fine-tuning of dosages to suit different requirements.Thus,the platform is versatile and efficient,with potential for further development.
基金supported by the National Natural Science Foundation of China(Nos.82072065 and 81471784).
文摘Recently,the development of chemodynamic therapy(CDT)offers a potential approach for fighting bacteria and treating infectious diseases,in which those CDT nanoagents can catalyze the generation of hydroxyl radicals(·OH)to destroy bacteria.In this work,to improve the efficiency of CDT,we have designed a new kind of metformin(Met)-capped two-dimensional Cu_(2)(OH)_(3)Cl nanosheets(CuOHCl-Met NSs)with good monodispersity,highly positive charge,and good biocompatibility for improving antibacterial effect and accelerating wound healing.With the capped Met,CuOHCl-Met NSs can effectively kill bacteria under a low concentration(6μg·mL^(−1))and a short treatment time(in 15 min),showing great advantages over the counterpart without Met.In vivo results demonstrated that CuOHCl-Met NSs accelerated the tissue regeneration of staphylococcus aureus-infected dermal wounds.This study provides a new pathway for improving efficiency of CDT nanoagent through using old drug.
基金This work was financially supported by the National Natural Sciences Foundation of China(Nos.31971308,81960769 and U1903211)the National S&T Major Project(No.2019ZX09301-147)+1 种基金the Sichuan Science and Technology Program(No.2022YFS0007)the Luzhou Science and Technology Plan(No.2018CDLZ-10).
文摘Due to the hypoxic state of the tumor microenvironment(TME),photodynamic therapy(PDT)suffers from insufficient ROS production.The metal-polyphenol network-mediated Fenton reaction can generate reac-tive oxygen species(ROS)by consuming H_(2)O_(2) in TME,improving the inadequate ROS generation problem of PDT.Therefore,synergistic therapy combining PDT and Fenton response-based CDT is a promising ap-proach for cancer treatment.Herein,a metal-polyphenol nanocomposite was deposited with gallic acid grafted hyaluronic acid and Fe^(3+) to contrast a Ce6 nano-delivery system(Ce6@HSF NPs)for melanoma synergistic therapy.Ce6@HSF NPs could be used as a Fenton reagent to induce the·OH production and enhance the PDT effect of Ce6 to a certain extent.After 4 h of cellular uptake,the fluorescence intensity of Ce6 in the Ce6@HSF NPs group was higher than 3 times that in the Ce6 group.The intracellular ROS generation level of the Ce6@HSF NPs(L)group combining CDT and PDT was higher than that of the Ce6 group and Ce6@HSF NPs group.In vitro and in vivo anti-melanoma studies show that Ce6@HSF NPs(L)group exhibited better anti-melanoma than other groups.Together,Ce6@HSF NPs provide a promising synergistic treatment potential for melanoma.
基金This work was financially supported by the National Natural Science Foundation of China(31771048,32071350)Fundamental Research Funds for the Central Universities(2232018A3-07,2232019A3-06)International Cooperation Fund of the Science and Technology Com-mission of Shanghai Municipality(19440741600).
文摘Osteosarcoma is a refractory bone disease in young people that needs the updating and development of effective treatment.Although nanotechnology is widely applied in cancer therapy,poor targeting and inadequate effi-ciency hinder its development.In this study,we prepared alendronate(ALD)/K7M2 cell membranes-coated hollow manganese dioxide(HMnO_(2))nanoparticles as a nanocarrier to load Ginsenoside Rh2(Rh2)for Mag-netic Resonance imaging(MRI)-guided immuno-chemodynamic combination osteosarcoma therapy.Subse-quently,the ALD and K7M2 cell membranes were successively modified on the surface of HMnO_(2) and loaded with Rh2.The tumor microenvironment(TME)-activated Rh2@HMnO_(2)-AM nanoparticles have good bone tumor-targeting and tumor-homing capabilities,excellent GSH-sensitive drug release profile and MRI capability,and attractive immuno-chemodynamic combined therapeutic efficiency.The Rh2@HMnO_(2)-AM nanoparticles can effectively trigger immunogenic cell death(ICD),activate CD4^(+)/CD8^(+)T cells in vivo,and upregulate BAX,BCL-2 and Caspase-3 in cellular level.Further results revealed that Rh2@HMnO_(2)-AM enhanced the secretion of IL-6,IFN-γand TNF-αin serum and inhibited the generation of FOXP3^(+)T cells(Tregs)in tumors.Moreover,the Rh2@HMnO_(2)-AM treatment significant restricted tumor growth in-situ tumor-bearing mice.Therefore,Rh2@HMnO_(2)-AM may serve as an effective and bio-friendly nanoparticle platform combined with immuno-therapy and chemodynamic therapy to provide a novel approach to osteosarcoma therapy.
基金National Natural Science Foundation of China(21971007)the Beijing Natural Science Foundation(2212044).C.T+1 种基金thanks the funding support from the National Natural Science Foundation of China(52122002 and 22005259)the Start-Up Grant(9610495)from City University of Hong Kong.
文摘Combining photodynamic therapy(PDT)with chemodynamic therapy(CDT)has been proven to be a promising strategy to improve the treatment efficiency of cancer,because of the synergistic therapeutic effect arising between the two modalities.Herein,we report an inorganic nanoagent based on ternary NiCoTi-layered double hydroxide(NiCoTi-LDH)nanosheets to realize highly efficient photodynamic/chemodynamic synergistic therapy.The NiCoTi-LDH nanosheets exhibit oxygen vacancy-promoted electron-hole separation and photogenerated holeinduced O_(2)-independent reactive oxygen species(ROS)generation under acidic circumstances,realizing in situ pH-responsive PDT.Moreover,due to the effective conversion between Co^(3+)and Co^(2+)caused by photogenerated electrons,the NiCoTi-LDH nanosheets catalyze the release of hydroxyl radicals(-OH)from H_(2)O_(2)through Fenton reactions,resulting in CDT.Laser irradiation enhances the catalyzed ability of the NiCoTi-LDH nanosheets to promote the ROS generation,resulting in a better performance than TiO_(2)nanoparticles at pH 6.5.In vitro and in vivo experimental results show conclusively that NiCoTi-LDH nanosheets plus irradiation lead to efficient cell apoptosis and significant inhibition of tumor growth.This study reports a new pH-responsive inorganic nanoagent with oxygen vacancy-promoted photodynamic/chemodynamic synergistic performance,offering a potentially appealing clinical strategy for selective tumor elimination.
基金supported by the National Natural Science Foundation of China(82172094)Funds of Sichuan Province for Distinguished Young Scholar(2021JDJQ0037,China)。
文摘Radiotherapy(RT) can potentially induce systemic immune responses by initiating immunogenic cell death(ICD) of tumor cells.However,RT-induced antitumor immunologic responses are sporadic and insufficient against cancer metastases.Herein,we construct multifunctional self-sufficient nanoparticles(MARS) with dual-enzyme activity(GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic relapse.In addition to limiting the Warburg effect to actualize starvation therapy,MARS catalyzes glucose to produce hydrogen peroxide(H_(2)O_(2)),which is then used in the Cu^(+)-mediated Fenton-like reaction and RT sensitization.RT and chemodynamic therapy produce reactive oxygen species in the form of radical storms,which have a robust ICD impact on mobilizing the immune system.Thus,when MARS is combined with RT,potent systemic antitumor immunity can be generated by activating antigen-presenting cells,promoting dendritic cells maturation,increasing the infiltration of cytotoxic T lymphocytes,and reprogramming the immuno suppre ssive tumor microenvironment.Furthermore,the synergistic therapy of RT and MARS effectively suppresses local tumor growth,increases mouse longevity,and results in a 90% reduction in lung metastasis and postoperative recurrence.Overall,we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.
基金the National Key R&D Program of China(No.2020YFA0908800)the National Natural Science Foundation of China(Nos.22174105 and 21974104)Large-scale Instrument and Equipment Sharing Foundation of Wuhan University.
文摘Malignant tumors are the main diseases threatening human life. Using precise theranostics to diagnose and cure tumors has emerged as a new method to improve patient survival. Based on the current development of precise tumor imaging, image-guided tumor therapy has received widespread attention because it is beneficial for developing precise treatment of tumors, has the potential to improve the efficacy of tumor therapy and reduce the incidence of adverse side effects. Nanoprobes, which are nanomaterial functionalized with specific biomolecules, have intrigued intense interest due to their great potential in monitoring biorecognition and biodetection evens. Benefiting from the unique advantages of nanomaterials, including the easy surface functionalization, the unique imaging performances, and the high drug loading capacity, nanoprobes have become a powerful tool to simultaneously realize tumor precise imaging, diagnosis, and therapy. This review introduces the non-invasive tumor precise imaging and highlights the recent advances of image-guided oncotherapy mediated by nanoprobes in anti-tumor drug delivery, tumor precise surgical navigation, chemodynamic therapy, and phototherapy. Finally, a perspective on the challenge and future direction of nanoprobes in imaging-guided tumor theranostics is also discussed.
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(22171001,22305001,51972001,52372073)the Natural Science Foundation of Anhui Province of China(2108085MB49).
文摘The realization of real-time thermal feedback for monitoring photothermal therapy(PTT)under near-infrared(NIR)light irradiation is of great interest and challenge for antitumor therapy.Herein,by assembling highly efficient photothermal conversion gold nanorods and a temperature-responsive probe((E)-4-(4-(diethylamino)styryl)-1-methylpyridin-1-ium,PyS)within MOF-199,an intelligent nanoplatform(AMPP)was fabricated for simultaneous chemodynamic therapy and NIR light-induced temperature-feedback PTT.The fluorescence intensity and temperature of the PyS probe are linearly related due to the restriction of the rotation of the characteristic monomethine bridge.Moreover,the copper ions resulting from the degradation of MOF-199 in an acidic microenvironment can convert H_(2)O_(2)into•OH,resulting in tumor ablation through a Fenton-like reaction,and this process can be accelerated by increasing the temperature.This study establishes a feasible platform for fabricating highly sensitive temperature sensors for efficient temperature-feedback PTT.
基金financially supported by the National Key Research and Development Program of China(No.2022YFB3804500)the National Natural Science Foundation of China(Nos.52102354,52102180,52202353,and 52372273)the Science and Technology Development Planning Project of Jilin Province(Nos.20220101070JC,20220508089RC,and 20210402046GH).
文摘Chemodynamic therapy(CDT),an inventive approach to cancer treatment,exploits innate chemical processes to trigger cell death through the generation of reactive oxygen species(ROS).While offering advantages over conventional treatments,the optimization of CDT efficacy presents challenges stemming from suboptimal catalytic efficiency and the counteractive ROS scavenging effect of intracellular glutathione(GSH).In this study,we aim to address this dual challenge by delving into the role of copper valence states in CDT.Leveraging the unique attributes of copper-based nanoparticles,especially zero-valent copper nanoparticles(CuPd NPs),we aim to enhance the therapeutic potential of CDT.Our experiments reveal that zero-valent CuPd NPs outperform divalent copper nanoparticles(Ox-CuPd NPs)by displaying superior catalytic performance and sustaining ROS generation through a dual approach integrating peroxidase-like(POD-like)activity and Cu+release.Notably,zero-valent NPs exhibit enhanced GSH depletion compared to their divalent counterparts,thereby intensifying CDT and inducing ferroptosis,ultimately resulting in high-efficiency tumor growth inhibition.These findings reveal the impact of valences on CDT,providing novel insights for the optimization and design of CDT agents.
基金This work is financially supported by the National Natu-ral Science Foundation of China(Nos.51901239 and 52001076)the Shanghai Committee of Science and Technology,China(No.20S31901200)+1 种基金the S&T Innovation 2025 Major Special Programme of Ningbo(No.2020Z095)the S&T Industrial Programme of Cixi(No.2019gy01).
文摘Osteosarcoma(OS)is a malignant tumor with a high rate of recurrence.Recently,biodegradable Mg-based implants have become a new therapeutic platform for bone-related diseases.However,poor biosafety and deficient intelligent tumor-killing ability of Mg-based implants are still the main challenges for the pre-cise treatment of OS.Herein,based on the excellent catalytic and photothermal conversion properties of nanozyme ferric oxide(Fe_(3)O_(4)),a novel two-step hydrothermal method for in situ preparation of Fe_(3)O_(4)nanosheets on the surface of plasma electrolytic oxidation(PEO)-treated Mg alloy using Mg-Fe layered double hydroxides(Mg-Fe LDH)as precursor was proposed.Compared with Mg alloy,there were no obvious corrosion cracks on the surface of Fe_(3)O_(4)nanosheets-coated Mg alloy(Fe_(3)O_(4)-NS)immersed in 0.9 wt.%NaCl for 14 days,which demonstrated the corrosion resistance of Mg alloy was significantly enhanced.Cytocompatibility experiments and hemolysis assay confirmed the great biocompatibility of Fe_(3)O_(4)-NS,especially,hemolysis ratio was lower than 1%.Meanwhile,Fe_(3)O_(4)-NS presented excellent cat-alytic oxidation capacity in the presence of H_(2)O_(2),and its temperature can significantly increase from 27℃to approximately 56℃under NIR irradiation.Therefore,intelligent responsive Fe_(3)O_(4)nanosheets-engineered Mg-based implants demonstrated excellent antitumor properties in vivo and in vitro due to their photothermal and chemodynamic synergetic effects.This study provides a novel approach for the preparation of Fe_(3)O_(4)coatings on the surface of Mg alloys and a new strategy for the treatment of OS.
基金financially supported by the National Natural Science Foundation of China (Nos. 81803723, 51903062)Guangdong Basic and Applied Basic Research Foundation (No. 2019B1515120006)+2 种基金Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2019), Innovation and Entrepreneurship Team Leads the Pilot Program of Zhanjiang (No. 2020LHJH005)Discipline Construction Project of Guangdong Medical University (No. 4SG22002G)Science and Technology Projects of Guangzhou (No. 202102020757)。
文摘Cu_(2-x)S nanostructures have been intensively studied as outstanding chemodynamic therapy(CDT)and good photothermal therapy(PTT)antibacterial agents due to their highly efficient Cu(Ⅰ)-initiated Fenton-like catalytic activity and good photothermal conversion property.However,they still suffer from shortage of Cu(Ⅰ)supply in the long-term and comparatively low inherent photothermal conversion efficiency.Herein,we constructed a self-enhanced synergistic PTT/CDT nanoplatform(Cu_(1.94)S@MPN)by coating Cu_(1.94)S nanoparticles with Fe(Ⅲ)/tannic acid based metal-polyphenol networks(MPN).Activated by the acidic bacterial infection microenvironment,Cu_(1.94)S@MPN could be decomposed to continuously release Cu(Ⅱ),Fe(Ⅲ)ions and tannic acid.As the result of tannic acid-involved Cu and Fe redox cycling,Cu(Ⅰ)/Fe(Ⅱ)-rich CDT could be achieved through the highly accelerated catalytic Fenton/Fenton-like reactions.More importantly,experimental results demonstrated that Cu_(1.94)S@MPN exhibited both excellent photothermal antibacterial and photothermal-enhanced CDT properties to eradicate bacteria in vitro and in vivo.Overall,this novel nanotherapeutics has great potential to become a clinic candidate for anti-infective therapy in future.
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.
基金supported by the Laboratory Animal Welfare and Ethics Committee of the Clinical Center of Shanghai First People's Hospital (No. 2020AWS0065)financially supported by the National Natural Science Foundation of China (Nos. 21978165, 92156020)+1 种基金Science and Technology Commission of Shanghai (No. 20DZ2255900)Class Ⅲ Peak Discipline of Shanghai—Materials Science and Engineering (High-Energy Beam Intelligent Processing and Green Manufacturing)。
文摘Diabetic patients often have problems such as residual tumor and wound infection after tumor resection,causing severe clinical problems.It is urgent to develop effective therapies to reach oncotherapy/antiinfection/promotion of wound healing combined treatment.Herein,we propose CS/MnO_(2)-GO_x (CMGO_x)nanocatalysts for the specific catalytic generation of ~·OH to inhibit tumors and bacteria in a hyperglycemic environment.The good biocompatible chitosan (CS),as a carrier for the catalyst,exhibits excellent antibacterial effect as well as promotes wound healing.Glucose oxidase (GO_x) is loaded on the surface of CS nanoparticles to generate H_(2)O_(2) and gluconic acid by consuming glucose (starvation therapy,ST) and O_(2).The MnO_(2) depletes glutathione (GSH) to produce Mn^(2+),amplifying oxidative stress and further promoting the activity of Mn^(2+)-mediated Fenton-like reaction to produce~·OH (chemodynamic therapy,CDT)in weak acidic environment.Moreover,the produced gluconic acid lowers the p H of the environment,enhancing chemodynamic therapy (ECDT).The tumor cells and bacteria are efficiently eliminated by the synergistic effect of ST and ECDT.The MnO_(2) nanoparticles at neutral environment decomposes H_(2)O_(2) into O_(2),which cooperate with CS to promote healing.The self-enhanced cascade reaction of CMGO_x in situ exhibits excellent effects of antitumor/antibacterial therapy and promotion of wound healing,offering a promising integrated treatment for diabetic patients after tumor surgical resection.
基金supported by the National Natural Science Foundation of China(51720105015,51672269,51929201,51922097,51772124 and 51872282)the Science and Technology Cooperation Project between Chinese and Australian Governments(2017YFE0132300)+4 种基金the Science and Technology Development Planning Project of Jilin Province(20170101188JC and 20180520163JH)the Key Research Program of Frontier Sciences,CAS(YZDY-SSW-JSC018)the Youth Innovation Promotion Association of CAS(2017273)the Overseas,Hong Kong&Macao Scholars Collaborated Researching Fund(21728101)the CAS-Croucher Funding Scheme for Joint Laboratories(CAS18204)。
文摘Inspired by the limitations of nanoparticles in cancer treatment caused by their low therapeutic effects and biotoxicity,biocompatible and photothermal enhanced copper oxide-decorated carbon nanospheres(CuO@CNSs)with doxorubicin hydrochloride(DOX)loading were constructed.CNSs as photothermal agents were synthesized by a hydrothermal reaction.CuO was adsorbed on the surface of CNSs,which improved the photothermal conversion efficiency due to the electron transitions between C-2 p and Cu-3 d.In addition,CuO would release Cu2+ions in the tumor microenvironment,which could produce hydroxyl radical(·OH)to induce cancer cells apoptosis via Haber-Weiss and Fenton-like reactions.DOX as a chemotherapeutic agent was located on the surface of CuO@CNSs by electrostatic adsorption and released quickly in the tumor microenvironment to kill cancer cells.The CuO@CNSs-DOX nanoplatforms realized the combination therapy of photothermal therapy(PTT),chemodynamic therapy(CDT),and chemotherapy(CT),which have strong potential for cancer treatment.
基金supported by National Natural Science Foundation of China(Nos 22275129 and 21975165)the Sichuan Science and Technology Innovation Foundation(2021JDTD0015).
文摘Cu-mediated chemodynamic therapy(CDT)has attracted prominent attention owing to its advantages of pH independence and high efficiency comparing to Fe-mediated CDT,while the application of Cu-based CDT agents was impeded due to the high copper consumption caused by the metabolism loss of copper and the resultant potential toxicity.Herein,we developed a new copper-mediated CDT agent with extremely low Cu usage by anchoring copper on cross-linked lipoic acid nanoparticles(Cu@cLAs).After endocytosis into tumor cells,the Cu@cLAs were dissociated into LA and dihydrolipoic acid(DHLA)(reduced form of LA)and released Cu^(2+)and Cu+(oxidized form of Cu^(2+)),the two redox couples recycled each other in cells to achieve the efficient killing of cancer cells by delaying metabolic loss and increasing the ROS level of tumor cells.The self-recycling was confirmed in cells by the sustained high Cu/DHLA content and persistent ROS generation process.The antitumor study based on the MCF-7/R nude mice gave the Cu@cLAs a tumor inhibitory rate up to 77.9%at the copper of 0.05 mg kg^(−1),the first dosage reported so far lower than that of normal serum copper(0.83±0.21 mg kg^(−1)).This work provides not only a new promising clinical strategy for the copper excessive use in copper-mediated CDT,but also gives a clue for other metal mediated disease therapies with the high metal consumption.
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.
