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
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 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(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
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
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
The enhanced permeability and retention(EPR)effect alone is not enough for nanoparticles to reach the target.Combination of active and passive targeting may be an effective drug delivery route.Hollow ferric-tannic aci...The enhanced permeability and retention(EPR)effect alone is not enough for nanoparticles to reach the target.Combination of active and passive targeting may be an effective drug delivery route.Hollow ferric-tannic acid complex nanocapsules(HFe-TA)may effectively degrade and release Fe^(2+) ions,Fe^(2+)ions induce the production of·OH,however,the fenton reaction needs amount of H_(2)O_(2)to enhance chemodynamic therapy.Due to their deficiencies,such nanoparticles cannot realize intravenous drug delivery.Here,the mesothelin-targeted membrane(MTM)was constructed to realize accurate delivery nano-system,mesothelin antibody was expressed on the 293T cell membrane to prepare a MTM.Lactate oxidase(Lox)was loaded on HFe-TA to obtain Lox@HFe-TA.Lox@HFe-TA was coated with MTM to develop the MTM nanosystem.Tirapazamine(TPZ)therapy also requires hypoxia circumstance.The MTM nanosystem combined with TPZ can significantly kill tumour cells and inhibit metastasis in vivo and in vitro.We also tested the biological safety of the treatment.In this study,we overcame the EPR defects via the MTM nanosystem,which can realize acute targeted delivery to the tumour site,lactate depletion,promoted reactive oxygen species(ROS)induction,enhanced the effect of TPZ,demonstrating a potential synergistic combination of cancer therapy with better efficacy and biosafety.展开更多
This study introduces multifunctional silica nanoparticles that exhibit both high photothermal and chemodynamic therapeutic activities,in addition to luminescence.The activity of the silica nanoparticles is derived fr...This study introduces multifunctional silica nanoparticles that exhibit both high photothermal and chemodynamic therapeutic activities,in addition to luminescence.The activity of the silica nanoparticles is derived from their plasmonic properties,which are a result of infusing the silica nanoparticles with multiple Cu2-xS cores.This infusion process is facilitated by a recoating of the silica nanoparticles with a cationic surfactant.The key factors that enable the internal incorporation of the Cu2-xS cores and the external deposition of red-emitting carbon dots are identified.The Cu2-xS cores within the silica nanoparticles exhibit both self-boosting generation of reactive oxygen species and high photothermal conversion efficacy,which are essential for photothermal and chemodynamic activities.The silica nanoparticles’small size(no more than 70 nm)and high colloidal stability are prerequisites for their cell internalization.The internalization of the red-emitting silica nanoparticles within cells is visualized using fluorescence microscopy techniques.The chemodynamic activity of the silica nanoparticles is associated with their dark cytotoxicity,and the mechanisms of cell death are evaluated using an apoptotic assay.The photothermal activity of the silica nanoparticles is demonstrated by significant cell death under near-infrared(1064 nm)irradiation.展开更多
Although endogenous H_(2)O_(2) is overexpressed in tumor tissue,the amount of endogenous H_(2)O_(2) is still insufficient for chemodynamic therapy(CDT).In addition,the abundant cellular glutathione(GSH)could also cons...Although endogenous H_(2)O_(2) is overexpressed in tumor tissue,the amount of endogenous H_(2)O_(2) is still insufficient for chemodynamic therapy(CDT).In addition,the abundant cellular glutathione(GSH)could also consume·OH for reduced CDT.Thus,the elevation of H_(2)O_(2) and the consumption of GSH in tumor tissue are essential for the increased·OH yield and amplified CDT efficacy.In this paper,hostguest interactions based supramolecular complexes self-assemblies(SCSAs)were fabricated by incorporating cinnamaldehyde(CA)and PEG-modified cyclodextrin host units(m PEG-CD-CA)with ferrocene-(phenylboronic acid pinacol ester)conjugates(Fc-BE)on the basis of CD-induced host-guest interactions.After being internalized by cancer cells,CA can be released from SCSAs through the p H-responsive acetal linkage,elevating the H2O2level by activating NADPH oxidase.Then,Fc can catalyze the H_(2)O_(2) to higher cytotoxic hydroxyl radicals(·OH).Moreover,quinone methide(QM)can be produced through H_(2)O_(2)-induced aryl boronic ester rearrangement and further consume the antioxidant GSH.In vitro and in vivo experiments demonstrate that SCSAs can be provided as potential amplified CDT nanoagents.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
Cancer is a severe disease,which have troubled human being for a long time.The development of nanotechnology has provided a new way for cancer treatment.It is a promising strategy to integrate imaging and therapeutic ...Cancer is a severe disease,which have troubled human being for a long time.The development of nanotechnology has provided a new way for cancer treatment.It is a promising strategy to integrate imaging and therapeutic functions into one single nanoplatform to achieve efficient combination of diagnosis and treatment.Herein,we exploited novel CuMo_(2)S_(3)-PEG-Gd nanocomposites(NCs)for magnetic resonance imaging(MRI),guiding the photothermal therapy(PTT)/photodynamic therapy(PDT)/chemodynamic therapy(CDT).The experimental results showed that CuMo_(2)S_(3)-PEG-Gd NCs have a high photothermal conversion efficiency(40.6%),excellent biocompatibility and good biosecurity.The CuMo_(2)S_(3)-PEGGd NCs exhibited a clear MRI performance for tumor due to connecting Gd,which can guide in vivo therapy to improve the therapeutic effect.Moreover,both in vitro and in vivo therapeutic results of CuMo_(2)S_(3)-PEG-Gd NCs exhibited that the PTT/PDT/CDT achieved a remarkably synergistic effect,which could efficiently inhibit the tumor growth.Thus,CuMo_(2)S_(3)-PEG-Gd NCs,which integrated imaging with multiple therapies,have a good potential as theranostic agent for tumor.展开更多
Chemodynamic therapy(CDT)is an emerging endogenous stimulation activated tumor treatment approach that exploiting iron-containing nanomedicine as catalyst to convert hydrogen peroxide(H_(2)O_(2))into toxic hydroxyl ra...Chemodynamic therapy(CDT)is an emerging endogenous stimulation activated tumor treatment approach that exploiting iron-containing nanomedicine as catalyst to convert hydrogen peroxide(H_(2)O_(2))into toxic hydroxyl radical(·OH)through Fenton reaction.Due to the unique characteristics(weak acidity and the high H_(2)O_(2) level)of the tumor microenvironment,CDT has advantages of high selectivity and low side effect.However,as an important substrate of Fenton reaction,the endogenous H_(2)O_(2) in tumor is still insufficient,which may be an important factor limiting the efficacy of CDT.In order to optimize CDT,various H_(2)O_(2)-generating nanomedicines that can promote the production of H_(2)O_(2) in tumor have been designed and developed for enhanced CDT.In this review,we summarize recently developed nanomedicines based on catalytic enzymes,nanozymes,drugs,metal peroxides and bacteria.Finally,the challenges and possible development directions for further enhancing CDT are prospected.展开更多
Critical bone defects caused by extensive excision of malignant bone tumor and the probability of tumor recurrence due to residual tumor cells make malignant bone tumor treatment a major clinical challenge.The present...Critical bone defects caused by extensive excision of malignant bone tumor and the probability of tumor recurrence due to residual tumor cells make malignant bone tumor treatment a major clinical challenge.The present therapeutic strategy concentrates on implanting bone substitutes for defect filling but suffers from failures in both enhancing bone regeneration and inhibiting the growth of tumor cells.Herein,Cu and Mn-doped borosilicate nanoparticles(BSNs)were developed for syncretic bone repairing and anti-tumor treatment,which can enhance bone regeneration through the osteogenic effects of Cu^(2+) and Mn^(3+) ions and meanwhile induce tumor cells apoptosis through the hydroxyl radicals produced by the Fenton-like reactions of Cu^(2+) and Mn^(3+) ions.In vitro study showed that both osteogenic differentiation of BMSCs and angiogenesis of endothelial cells were promoted by BSNs,and consistently the critical bone defects of rats were efficiently repaired by BSNs through in vivo evaluation.Meanwhile,BSNs could generate hydroxyl radicals through Fenton-like reactions in the simulated tumor microenvironment,promote the generation of intracellular reactive oxygen species,and eventually induce tumor cell apoptosis.Besides,subcutaneous tumors of mice were effectively inhibited by BSNs without causing toxic side effects to normal tissues and organs.Altogether,Cu and Mn-doped BSNs developed in this work performed dual functions of enhancing osteogenesis and angiogenesis for bone regeneration,and inhibiting tumor growth for chemodynamic therapy,thus holding a great potential for syncretic bone repairing and anti-tumor therapy.展开更多
Chemodynamic therapy kills cancer cells with reactive oxygen species generated by endogenous triggers in the tumor microenvironment.Although chemodynamic therapy is blossoming in recent years,their therapy process sti...Chemodynamic therapy kills cancer cells with reactive oxygen species generated by endogenous triggers in the tumor microenvironment.Although chemodynamic therapy is blossoming in recent years,their therapy process still faces a series of hampers.The unknown catalytic activity of chemodynamic therapy reagents may lead to unpredictable therapy effects,so it is necessary to reveal the therapeutic mechanism of chemodynamic therapy and develop self-monitoring probes.In this mini-review,we summarize and illustrate the most recent progress of chemodynamic therapy,focusing on the applications of magnetic imaging and optical imaging probe for monitoring cancer chemodynamic therapy.Furthermore,we also discuss the potential challenges and the further directions of this field.展开更多
In contrast to reactive oxygen species(ROS),the generation of oxygen-irrelevant free radicals is oxygen-and H2O2-independent in cell,which can offer novel opportunities to maximum the chemodynamic therapy(CDT)efficacy...In contrast to reactive oxygen species(ROS),the generation of oxygen-irrelevant free radicals is oxygen-and H2O2-independent in cell,which can offer novel opportunities to maximum the chemodynamic therapy(CDT)efficacy.Herein,an H2O2-independent“functional reversion”strategy based on tumor microenvironment(TME)-toggled C-free radical generation for CDT is developed by confining astaxanthin(ATX)on the NiFe-layered double hydroxide(LDH)nanosheets(denoted as ATX/LDH).The unique ATX/LDH can demonstrate outstanding TME-responsive C-free radical generation performance by proton coupled electron transfer(PCET),owing to the specific ATX activation by unsaturated Fe sites on the LDH nanosheets formed under TME.Significantly,the Brönsted base sites of LDH hydroxide layers can promote the generation of neutral ATX C-free radicals by capturing the protons generated in the ATX activation process.Conversely,ATX/LDH maintain antioxidant performance to prevent normal tissue cancerization due to the synergy of LDH nanosheets and antioxidative ATX.In addition,C-free radical can compromise the antioxidant defense in cells to the maximum extent,compared with ROS.The free radicals burst under TME can significantly elevate free radical stress and induce cancer cell apoptosis.This strategy can realize TME-toggled C free radical generation and perform free radical stress enhanced CDT.展开更多
Chemodynamic therapy (CDT) has attracted tremendous interest in cancer therapy because it is independent of oxygen and photoirradiation. However, the therapeutic efficacy of CDT is restricted by insufficient H_(2)O_(2...Chemodynamic therapy (CDT) has attracted tremendous interest in cancer therapy because it is independent of oxygen and photoirradiation. However, the therapeutic efficacy of CDT is restricted by insufficient H_(2)O_(2) levels in tumor cells. Herein, employing endogenous GSH as a template and cationic polymeric chitosan (CS) as crosslinker and stabilizer exhibiting easy cell uptake, red luminescent gold nanoclusters (denoted CS-GSH@AuNCs) were successfully synthesized in HeLa cells. The in situ synthesized CS-GSH@AuNCs exhibited both superoxidase dismutase (SOD) and peroxidase (POD)-like activity, which could promote the production of H_(2)O_(2) from superoxide anion radicals (O_(2)^(·-)) and then ^(·)OH. The combination of GSH elimination and H_(2)O_(2) elevation boosted the generation of ^(·)OH, which could trigger cancer cell apoptosis and death. The enzyme-like activity of CS-GSH@AuNCs could be effectively activated under acidic conditions, and showed a high killing effect on tumor cells but minimal toxicity to normal cells. The developed GSH consumption and ^(·)OH promotion theranostic platform is an innovative route for enhanced CDT by the amplification of oxidative stress.展开更多
In recent years,starvation-primed chemodynamic therapies(ST-CDT)have become a hot topic in the wake of many discoveries related to the aberrant metabolism of cancer cells and their resistance to traditional chemother-...In recent years,starvation-primed chemodynamic therapies(ST-CDT)have become a hot topic in the wake of many discoveries related to the aberrant metabolism of cancer cells and their resistance to traditional chemother-apies,as well as altered redox signaling within tumor cells.Nanotechnology platforms are in a unique position to exploit these interrelated phenomena to realize a therapeutic effect;few therapeutic modalities are able to deliver multiple drugs simultaneously outside of nanotechnology,a basic requirement when striving to exploit a complex,interactive system such as a cancer cell.In this review,the pertinent mechanisms of ST and CDT,as well as the important interactions between these two therapies,are discussed.We outline how these therapies may work synergistically or antagonistically,depending on both the therapeutic design and the system of reactions involved.Lastly,specific applications that nanotechnology is particularly well-suited are given,which may offer improvement over clinical state-of-the-art.Such considerations are important,as nanotechnology has historically encountered great difficulty in clinical translation.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the mission book of promotion program of basic and clinical collaborative research of Anhui Medical University(No.2022xkjT028)Anhui Provincial Scientific Research Preparation Plan Project(No.2022AH051171)+6 种基金the Anhui Provincial Natural Science Foundation(No.2208085MH240)Postgraduates of Colleges and Universities in Anhui Province(No.YJS20210308)the National Natural Science Foundation of China(No.81602425)the Anhui Quality Engineering Project(Nos.2020jyxm0898,2020jyxm0910,and 2019kfkc334)the Anhui Medical University Clinical Research Project(No.2020xkj176)the Anhui Health Soft Science Research Project(No.2020WR01003)the Key Research and Development Program of Anhui Province(No.201904a07020045).
文摘The enhanced permeability and retention(EPR)effect alone is not enough for nanoparticles to reach the target.Combination of active and passive targeting may be an effective drug delivery route.Hollow ferric-tannic acid complex nanocapsules(HFe-TA)may effectively degrade and release Fe^(2+) ions,Fe^(2+)ions induce the production of·OH,however,the fenton reaction needs amount of H_(2)O_(2)to enhance chemodynamic therapy.Due to their deficiencies,such nanoparticles cannot realize intravenous drug delivery.Here,the mesothelin-targeted membrane(MTM)was constructed to realize accurate delivery nano-system,mesothelin antibody was expressed on the 293T cell membrane to prepare a MTM.Lactate oxidase(Lox)was loaded on HFe-TA to obtain Lox@HFe-TA.Lox@HFe-TA was coated with MTM to develop the MTM nanosystem.Tirapazamine(TPZ)therapy also requires hypoxia circumstance.The MTM nanosystem combined with TPZ can significantly kill tumour cells and inhibit metastasis in vivo and in vitro.We also tested the biological safety of the treatment.In this study,we overcame the EPR defects via the MTM nanosystem,which can realize acute targeted delivery to the tumour site,lactate depletion,promoted reactive oxygen species(ROS)induction,enhanced the effect of TPZ,demonstrating a potential synergistic combination of cancer therapy with better efficacy and biosafety.
基金funded by RFBR and CNR, project number 20-53-7802.
文摘This study introduces multifunctional silica nanoparticles that exhibit both high photothermal and chemodynamic therapeutic activities,in addition to luminescence.The activity of the silica nanoparticles is derived from their plasmonic properties,which are a result of infusing the silica nanoparticles with multiple Cu2-xS cores.This infusion process is facilitated by a recoating of the silica nanoparticles with a cationic surfactant.The key factors that enable the internal incorporation of the Cu2-xS cores and the external deposition of red-emitting carbon dots are identified.The Cu2-xS cores within the silica nanoparticles exhibit both self-boosting generation of reactive oxygen species and high photothermal conversion efficacy,which are essential for photothermal and chemodynamic activities.The silica nanoparticles’small size(no more than 70 nm)and high colloidal stability are prerequisites for their cell internalization.The internalization of the red-emitting silica nanoparticles within cells is visualized using fluorescence microscopy techniques.The chemodynamic activity of the silica nanoparticles is associated with their dark cytotoxicity,and the mechanisms of cell death are evaluated using an apoptotic assay.The photothermal activity of the silica nanoparticles is demonstrated by significant cell death under near-infrared(1064 nm)irradiation.
基金supported by the National Natural Science Foundation of China(Nos.21801162,22071197,22022107)Natural Science Basic Research Plan in Shaanxi Province of China(No.2020JC20)。
文摘Although endogenous H_(2)O_(2) is overexpressed in tumor tissue,the amount of endogenous H_(2)O_(2) is still insufficient for chemodynamic therapy(CDT).In addition,the abundant cellular glutathione(GSH)could also consume·OH for reduced CDT.Thus,the elevation of H_(2)O_(2) and the consumption of GSH in tumor tissue are essential for the increased·OH yield and amplified CDT efficacy.In this paper,hostguest interactions based supramolecular complexes self-assemblies(SCSAs)were fabricated by incorporating cinnamaldehyde(CA)and PEG-modified cyclodextrin host units(m PEG-CD-CA)with ferrocene-(phenylboronic acid pinacol ester)conjugates(Fc-BE)on the basis of CD-induced host-guest interactions.After being internalized by cancer cells,CA can be released from SCSAs through the p H-responsive acetal linkage,elevating the H2O2level by activating NADPH oxidase.Then,Fc can catalyze the H_(2)O_(2) to higher cytotoxic hydroxyl radicals(·OH).Moreover,quinone methide(QM)can be produced through H_(2)O_(2)-induced aryl boronic ester rearrangement and further consume the antioxidant GSH.In vitro and in vivo experiments demonstrate that SCSAs can be provided as potential amplified CDT nanoagents.
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This work was financially supported by the National Natural Science Foundation of China(Nos.21978165 and 22081340412).
文摘Cancer is a severe disease,which have troubled human being for a long time.The development of nanotechnology has provided a new way for cancer treatment.It is a promising strategy to integrate imaging and therapeutic functions into one single nanoplatform to achieve efficient combination of diagnosis and treatment.Herein,we exploited novel CuMo_(2)S_(3)-PEG-Gd nanocomposites(NCs)for magnetic resonance imaging(MRI),guiding the photothermal therapy(PTT)/photodynamic therapy(PDT)/chemodynamic therapy(CDT).The experimental results showed that CuMo_(2)S_(3)-PEG-Gd NCs have a high photothermal conversion efficiency(40.6%),excellent biocompatibility and good biosecurity.The CuMo_(2)S_(3)-PEGGd NCs exhibited a clear MRI performance for tumor due to connecting Gd,which can guide in vivo therapy to improve the therapeutic effect.Moreover,both in vitro and in vivo therapeutic results of CuMo_(2)S_(3)-PEG-Gd NCs exhibited that the PTT/PDT/CDT achieved a remarkably synergistic effect,which could efficiently inhibit the tumor growth.Thus,CuMo_(2)S_(3)-PEG-Gd NCs,which integrated imaging with multiple therapies,have a good potential as theranostic agent for tumor.
基金the National Natural Science Foundation of China(Nos.32000991,51873150)the Young Elite Scientists Sponsorship Program by Tianjin(No.TJSQNTJ-2020-02)+2 种基金the Key project of Tianjin Foundational Research(JingJinJi)Program,China(No.19JCZDJC64100)the Key Project of Tianjin Nature Science Foundation(No.16JCZDJC35100)the Tianjin Research Innovation Project for Postgraduate Students(No.2020YJSB130)。
文摘Chemodynamic therapy(CDT)is an emerging endogenous stimulation activated tumor treatment approach that exploiting iron-containing nanomedicine as catalyst to convert hydrogen peroxide(H_(2)O_(2))into toxic hydroxyl radical(·OH)through Fenton reaction.Due to the unique characteristics(weak acidity and the high H_(2)O_(2) level)of the tumor microenvironment,CDT has advantages of high selectivity and low side effect.However,as an important substrate of Fenton reaction,the endogenous H_(2)O_(2) in tumor is still insufficient,which may be an important factor limiting the efficacy of CDT.In order to optimize CDT,various H_(2)O_(2)-generating nanomedicines that can promote the production of H_(2)O_(2) in tumor have been designed and developed for enhanced CDT.In this review,we summarize recently developed nanomedicines based on catalytic enzymes,nanozymes,drugs,metal peroxides and bacteria.Finally,the challenges and possible development directions for further enhancing CDT are prospected.
基金funded by National Key Research and Development Program of China(Grant No.2018YFC1106302 and 2018YFA0703100)National Natural Science Foundation of China(Grant No.51772210,U2001221,51802340,81871774 and 82072422)+1 种基金Frontier Science Key Research Programs of CAS(Grant No.QYZDB-SSW-JSC030)Shenzhen Fundamental Research Foundation(Grant No.JCYJ20200109114620793).
文摘Critical bone defects caused by extensive excision of malignant bone tumor and the probability of tumor recurrence due to residual tumor cells make malignant bone tumor treatment a major clinical challenge.The present therapeutic strategy concentrates on implanting bone substitutes for defect filling but suffers from failures in both enhancing bone regeneration and inhibiting the growth of tumor cells.Herein,Cu and Mn-doped borosilicate nanoparticles(BSNs)were developed for syncretic bone repairing and anti-tumor treatment,which can enhance bone regeneration through the osteogenic effects of Cu^(2+) and Mn^(3+) ions and meanwhile induce tumor cells apoptosis through the hydroxyl radicals produced by the Fenton-like reactions of Cu^(2+) and Mn^(3+) ions.In vitro study showed that both osteogenic differentiation of BMSCs and angiogenesis of endothelial cells were promoted by BSNs,and consistently the critical bone defects of rats were efficiently repaired by BSNs through in vivo evaluation.Meanwhile,BSNs could generate hydroxyl radicals through Fenton-like reactions in the simulated tumor microenvironment,promote the generation of intracellular reactive oxygen species,and eventually induce tumor cell apoptosis.Besides,subcutaneous tumors of mice were effectively inhibited by BSNs without causing toxic side effects to normal tissues and organs.Altogether,Cu and Mn-doped BSNs developed in this work performed dual functions of enhancing osteogenesis and angiogenesis for bone regeneration,and inhibiting tumor growth for chemodynamic therapy,thus holding a great potential for syncretic bone repairing and anti-tumor therapy.
基金supported by the National Natural Science Foundation of China(Nos.21804039 and 51872088)the Science and Technology Project of Hunan Province,China(No.2020RC3022)the Fundamental Research Funds for the Central Universities,China.
文摘Chemodynamic therapy kills cancer cells with reactive oxygen species generated by endogenous triggers in the tumor microenvironment.Although chemodynamic therapy is blossoming in recent years,their therapy process still faces a series of hampers.The unknown catalytic activity of chemodynamic therapy reagents may lead to unpredictable therapy effects,so it is necessary to reveal the therapeutic mechanism of chemodynamic therapy and develop self-monitoring probes.In this mini-review,we summarize and illustrate the most recent progress of chemodynamic therapy,focusing on the applications of magnetic imaging and optical imaging probe for monitoring cancer chemodynamic therapy.Furthermore,we also discuss the potential challenges and the further directions of this field.
基金the financial support from the National Natural Science Foundation of China(No.21571013,52073023,and 21805293)the National Basic Research Program(No.2014CB932101)+2 种基金the Program for Chang Jiang Scholars,Innovative Research Team in University(No.IRT1205)the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2019027)the Director Foundation of the Technical Institute of Physics and Chemistry,Chinese Academy of Sciences.
文摘In contrast to reactive oxygen species(ROS),the generation of oxygen-irrelevant free radicals is oxygen-and H2O2-independent in cell,which can offer novel opportunities to maximum the chemodynamic therapy(CDT)efficacy.Herein,an H2O2-independent“functional reversion”strategy based on tumor microenvironment(TME)-toggled C-free radical generation for CDT is developed by confining astaxanthin(ATX)on the NiFe-layered double hydroxide(LDH)nanosheets(denoted as ATX/LDH).The unique ATX/LDH can demonstrate outstanding TME-responsive C-free radical generation performance by proton coupled electron transfer(PCET),owing to the specific ATX activation by unsaturated Fe sites on the LDH nanosheets formed under TME.Significantly,the Brönsted base sites of LDH hydroxide layers can promote the generation of neutral ATX C-free radicals by capturing the protons generated in the ATX activation process.Conversely,ATX/LDH maintain antioxidant performance to prevent normal tissue cancerization due to the synergy of LDH nanosheets and antioxidative ATX.In addition,C-free radical can compromise the antioxidant defense in cells to the maximum extent,compared with ROS.The free radicals burst under TME can significantly elevate free radical stress and induce cancer cell apoptosis.This strategy can realize TME-toggled C free radical generation and perform free radical stress enhanced CDT.
基金supported by the National Natural Science Foundation of China (No. 22074007)。
文摘Chemodynamic therapy (CDT) has attracted tremendous interest in cancer therapy because it is independent of oxygen and photoirradiation. However, the therapeutic efficacy of CDT is restricted by insufficient H_(2)O_(2) levels in tumor cells. Herein, employing endogenous GSH as a template and cationic polymeric chitosan (CS) as crosslinker and stabilizer exhibiting easy cell uptake, red luminescent gold nanoclusters (denoted CS-GSH@AuNCs) were successfully synthesized in HeLa cells. The in situ synthesized CS-GSH@AuNCs exhibited both superoxidase dismutase (SOD) and peroxidase (POD)-like activity, which could promote the production of H_(2)O_(2) from superoxide anion radicals (O_(2)^(·-)) and then ^(·)OH. The combination of GSH elimination and H_(2)O_(2) elevation boosted the generation of ^(·)OH, which could trigger cancer cell apoptosis and death. The enzyme-like activity of CS-GSH@AuNCs could be effectively activated under acidic conditions, and showed a high killing effect on tumor cells but minimal toxicity to normal cells. The developed GSH consumption and ^(·)OH promotion theranostic platform is an innovative route for enhanced CDT by the amplification of oxidative stress.
基金supported by the National Key R&D Program of China(2018YFA0704000)Basic Research Program of Shenzhen(JCYJ20200109105620482,JCYJ20180507182413022,JCYJ20210324093815040)+1 种基金National Natural Science Foundation of China(21807074,8207198)Shenzhen Science and Technology Program(KQTD20190929172538530).
文摘In recent years,starvation-primed chemodynamic therapies(ST-CDT)have become a hot topic in the wake of many discoveries related to the aberrant metabolism of cancer cells and their resistance to traditional chemother-apies,as well as altered redox signaling within tumor cells.Nanotechnology platforms are in a unique position to exploit these interrelated phenomena to realize a therapeutic effect;few therapeutic modalities are able to deliver multiple drugs simultaneously outside of nanotechnology,a basic requirement when striving to exploit a complex,interactive system such as a cancer cell.In this review,the pertinent mechanisms of ST and CDT,as well as the important interactions between these two therapies,are discussed.We outline how these therapies may work synergistically or antagonistically,depending on both the therapeutic design and the system of reactions involved.Lastly,specific applications that nanotechnology is particularly well-suited are given,which may offer improvement over clinical state-of-the-art.Such considerations are important,as nanotechnology has historically encountered great difficulty in clinical translation.
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.