Designing and synthesizing nanomedicines with multi-modal tumor therapeutic capabilities is the key to cancer treatment.Herein,we prepared MICG nanoparticles(NPs)by assembling glucose oxidase(GOx)and indocyanine green...Designing and synthesizing nanomedicines with multi-modal tumor therapeutic capabilities is the key to cancer treatment.Herein,we prepared MICG nanoparticles(NPs)by assembling glucose oxidase(GOx)and indocyanine green(ICG)with manganese carbonate(MnCO_(3))NPs for starvation therapy cascaded chemodynamic therapy,enhanced phototherapy and immune activation.In MICG NPs,the GOx consumes intratumoral glucose resulting in starvation therapy,and simultaneously produces H_(2)O_(2)and decreases p H in tumor.The intensified acidic tumor environment promotes the decomposition of MnCO_(3)NPs to release Mn^(2+).The Mn^(2+)further catalyzes H_(2)O_(2)to generate hydroxyl radical for chemodynamic therapy.While ICG can generate singlet oxygen(^(1)O_(2))and heat to kill cancer cells through phototherapy mechanism.The hydroxyl radical and ^(1)O_(2) will further accelerate the oxidative stress,intensify immunogenic cell death,induce dendritic cell maturation,and thus activate systemic immunity.This work provides a new therapeutic platform for combining therapy of tumor.展开更多
Chemodynamic therapy(CDT),using Fenton agents to generate highly cytotoxic•OH from H_(2)O_(2)has been demonstrated as a powerful anticancer method.However,the insufficient endogenous H_(2)O_(2)in tumor cells greatly l...Chemodynamic therapy(CDT),using Fenton agents to generate highly cytotoxic•OH from H_(2)O_(2)has been demonstrated as a powerful anticancer method.However,the insufficient endogenous H_(2)O_(2)in tumor cells greatly limited its therapeutic effect.Herein,we prepared a pH-responsiveβ-lapachone-loaded ironpolyphenol nanocomplex(LIPN)through a one-pot method.β-Lapachone in LIPN selectively enhanced H_(2)O_(2)concentration in tumor cells,and ferrous ions cascadely generated abundant cytotoxic•OH.Therefore,LIPN with cascade amplification of reactive oxygen species(ROS)showed high chemodynamic cytotoxicity in tumor cells,efficiently improving the expression of damage-associated molecular patterns(DAMPs),and exerting strong immunogenic cell death(ICD).As a result,LIPN exhibited efficient tumor inhibition ability in 4T1 subcutaneous tumor model in vivo with great biocompatibility.Additionally,the infiltration of cytotoxic CD8^(+)T lymphocytes and inhibition of regulatory CD4^(+)FoxP3^(+)T lymphocytes in tumors demonstrated the activation of immunosuppressive tumor microenvironment by LIPN-induced ICD.Therefore,this work provided a new approach to enhance ICD of chemodynamic therapy through selective cascade amplification of ROS in cancer cells.展开更多
The complexity of cancer therapy has led to the emergence of combination therapy as a promising approach to enhance treatment efficacy and safety.The integration of glutathione(GSH)-activatable two-photon photodynamic...The complexity of cancer therapy has led to the emergence of combination therapy as a promising approach to enhance treatment efficacy and safety.The integration of glutathione(GSH)-activatable two-photon photodynamic therapy(TP-PDT)and chemodynamic therapy(CDT)offers the possibility to advance precision and efficacy in anti-cancer treatments.In this study,a GSH-activatable photosensitizer(PS),namely copper-elsinochrome(CuEC),is synthesized and utilized for combination second nearinfrared(NIR-II)TP-PDT/CDT.The Cu^(2+)acts as a“lock”,suppressing the fluorescence and^(1)O_(2)generation ability of EC in a normal physiological environment(“OFF”state).However,the overexpressed GSH in the tumor microenvironment acts as the“key”,resulting in the release of EC(“ON”state)and Cu^(+)(reduced by GSH).The released EC can be utilized for fluorescence imaging and TP-PDT under NIR-II(λ=1000 nm)two-photon excitation,while Cu+can generate highly toxic hydroxyl radicals(•OH)via Fenton-like reaction for CDT.Additionally,this process consumes GSH and diminishes the tumor’s antioxidant capacity,thereby augmenting the efficacy of combination therapy.The CuEC achieves significant tumor cell ablation in both 2D monolayer cells and 3D multicellular tumor spheres through the combination of NIR-II TP-PDT and CDT.展开更多
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
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
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
Chemodynamic therapy(CDT)relying on the transformation of endogenous hydrogen peroxide(H_(2)O_(2))into cytotoxic hydroxyl radicals(·OH)based on the catalysis of Fenton/Fenton-type reactions exhibits great potenti...Chemodynamic therapy(CDT)relying on the transformation of endogenous hydrogen peroxide(H_(2)O_(2))into cytotoxic hydroxyl radicals(·OH)based on the catalysis of Fenton/Fenton-type reactions exhibits great potentiality for cancer treatment.However,the inadequate H_(2)O_(2)supply and intricate redox homeostasis in tumor microenvironment(TME)severely impair the efficacy of CDT.Herein,we design selfassembled 1,2-distearoyl-sn-glycero-3-phosphoethanolamine conjugated polyethylene glycol(DSPE-PEG)-modified Fe(Ⅲ)-juglone nanoscale coordination polymers(FJP NCPs)as redox homeostasis disruptors for juglone-enhanced CDT.Responding to glutathione(GSH)-rich and acidic TME,the Fe^(2+)/Fe^(3+)-guided CDT and GSH consumption by Fe^(3+)are activated,resulting in·OH downstream and up-regulation of lipid peroxidation(LPO).In addition,the released juglone not only depletes GSH through Michael addition,but also elevates intracellular H_(2)O_(2)level for achieving·OH further bursting.With the impressive efficiency of GSH exhaustion and reactive oxygen species(ROS)storm generation,ferroptosis and apoptosis are significantly enhanced by FJP NCPs in vivo.In brief,this facile and efficient design for versatile nanoscale coordination polymers presents a novel paradigm for effectively elevating CDT efficiency and tumor synergistic therapy.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
Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting cancer.However,the potential application of bacterial therapy is hindered by the presence of instability an...Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting cancer.However,the potential application of bacterial therapy is hindered by the presence of instability and susceptibility to infections within bacterial populations.Furthermore,monotherapy is ineffective in completely eliminating complex cancer with multiple contributing factors.In this study,based on our discovery that spore shell(SS)of Bacillus coagulans exhibits excellent tumor-targeting ability and adjuvant activity,we develop a biomimetic spore nanoplatform to boost bacteria-mediated antitumor therapy,chemodynamic therapy and antitumor immunity for synergistic cancer treatment.In detail,SS is separated from probiotic spores and then attached to the surface of liposome(Lipo)that was loaded with hemoglobin(Hb),glucose oxidase(GOx)and JQ1to construct SS@Lipo/Hb/GOx/JQ1.In tumor tissue,highly toxic hydroxyl radicals(·OH)are generated via sequential catalytic reactions:GOx catalyzing glucose into H_(2)O_(2)and Fe^(2+)in Hb decomposing H_(2)O_(2)into·OH.The combination of·OH and SS adjuvant can improve tumor immunogenicity and activate immune system.Meanwhile,JQ1-mediated down-regulation of PD-L1 and Hb-induced hypoxia alleviation synergistically reshape immunosuppressive tumor microenvironment and potentiate immune response.In this manner,SS@Lipo/Hb/GOx/JQ1 significantly suppresses tumor growth and metastasis.To summarize,the nanoplatform represents an optimum strategy to potentiate bacteria-based cancer immunotherapy.展开更多
Photodynamic therapy(PDT)has significant advantages in treating primary tumors.However,the hypoxic tumor microenvironment hinders the generation of sufficient reactive oxygen species during PDT to effectively kill tum...Photodynamic therapy(PDT)has significant advantages in treating primary tumors.However,the hypoxic tumor microenvironment hinders the generation of sufficient reactive oxygen species during PDT to effectively kill tumor cells,further greatly limiting the applications of PDT in cancer treatment.Herein,we reported a temperature/pH dual controlled drug delivery system LPC@PCN@PDA/Fe^(3+)-AS1411 based on a porous coordination network(PCN(Mn))coated with polydopamine(PDA)and modified with an aptamer AS1411.β-lapachone(LPC)was loaded inside the PCN(Mn)framework,and Fe^(3+)was attached to the surface of the PDA coating.These nanoparticles(NPs)exhibited excellent multimodal cancer therapeutic effects and tumor targeting ability with their photo-and chemodynamic properties.The therapeutic effect can be enhanced by the production of sufficient oxygen by the internal hydrogen peroxide,which improves the photodynamic effect of the photosensitizer PCN(Mn)and the chemotherapy effect ofβ-lapachone.Notably,the conversion of Fe^(2+)to Fe^(3+)in the tumor cells exerts the Fenton effect,which generates hydroxyl radicals that cause lipid peroxidation in tumor cells and induce apoptosis,thus enhancing the chemodynamic therapeutic effect.In vitro and in vivo experiments revealed that the NPs demonstrated specific tumor targeting,excellent inhibition effect on tumor growth,and biocompatibility.Together,our findings can help develop an intelligent multifunctional therapeutic nanoplatform for cancer therapy.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
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,hostvip 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-vip 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
Metal-organic frameworks(MOFs)with high porosity,specific surface area,and unique topologies are highly regarded for their applications in photocatalysis,medical treatment,and environmental pollutant degradation.Howev...Metal-organic frameworks(MOFs)with high porosity,specific surface area,and unique topologies are highly regarded for their applications in photocatalysis,medical treatment,and environmental pollutant degradation.However,due to the limitations of the tumor microenvironment(TME),traditional MOFs have limited efficacy in this environment.This paper designs multi-metal oxide-based heterostructure POMOFs nanoreactors with a nesting doll-like structure.This new structure not only exhibits therapeutic effects in TME but also utilizes ultrasound(US)to enhance the release of reactive oxygen species(ROS)for CDT&SDT co-therapy,becoming an effective sound sensitizer for destroying tumor cells.In summary,our study proposes an idea for constructing multi-metal oxide-based heterostructure MOFs nanoreactors material with a nesting doll-like structure to enhance ROS release and synergistically treat tumor diseases.展开更多
An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(C...An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(Ce6)and triethoxy(1H,1H,2H,2H‑nonafluorohexyl)silane(TFS)was coated on the outer layer of UC,and then a layer of HKUST‑1 shell was coated.The obtained nanocomposite UC@Ce6/TFS@mSiO_(2)@HKUST‑1(noted as UCTSH)was used for the synergistic treatment of chemodynamic therapy(CDT)and photodynamic therapy(PDT).Interestingly,the nanostructures can specifically re lease Cu^(2+)in the acidic tumor microenvironment.Cu^(2+)reacts with excess hydrogen peroxide(H_(2)O_(2))in the tumor microenvironment to form cytotoxic hydroxyl radical.Secondly,Ce6,with the action of oxygen‑carrying TFS,selectively produces a large amount of singlet oxygen by 808 nm laser irradiation.UCTSH can enhance the anti‑tumor effects of PDT and CDT by increasing the production level of reactive oxygen species,without causing damage to normal cells.展开更多
Hepatocellular carcinoma(HCC)is the most common primary liver cancer with a poor prognosis.Chemotherapy is one of the first-line clinical therapeutic strategies for HCC.Still,the effectiveness of chemotherapy is hampe...Hepatocellular carcinoma(HCC)is the most common primary liver cancer with a poor prognosis.Chemotherapy is one of the first-line clinical therapeutic strategies for HCC.Still,the effectiveness of chemotherapy is hampered by the tumor immunosuppressive microenvironment and drug resistance caused by insufficient delivery.Herein,we developed a metal-drug self-delivery nanomedicine(FDAH)to improve the chemo/chemodynamic therapeutic efficacy of HCC.The core of FDAH is an iron-based nanoparticle chelated with two clinical drugs,Doxorubicin(DOX)and Plerixafor(AMD3100).Additionally,the nanomedicine is externally modified with a hyaluronic acid(HA)shell,which can prolong the circulation time of the nanoparticles in the bloodstream after intravenous administration.After entering the bloodstream,the nanomedicine reaches the tumor tissue through the EPR effect and is phagocytosed by the tumor cells via HA/CD44-specific interaction.Iron ion-mediated chemodynamic therapy is mediated by the Fenton reaction to generate ROS,causing an imbalance of redox homeostasis within the tumor cells and enhancing the sensitivity of tumor cells to DOX.In addition,AMD3100 intervenes in the CXCL12/CXCR4 axis to influence the infiltration level of immune cells and promote DOX chemotherapy in tumor cells.This work suggests that alleviating immunosuppression via a metal-drug self-delivery system of the CXCR4 inhibitor can effectively improve the DOX chemotherapy and iron ions-mediated chemodynamic therapy.展开更多
The inherent tumor microenvironment(TME)of hypoxia and high glutathione(GSH)hinders the production of reactive oxygen species(ROS),yet which are crucial roles to make the oxygen-independent chemodynamic therapy(CDT)ou...The inherent tumor microenvironment(TME)of hypoxia and high glutathione(GSH)hinders the production of reactive oxygen species(ROS),yet which are crucial roles to make the oxygen-independent chemodynamic therapy(CDT)outstanding.Herein,we constructed hyaluronic acid(HA)-modified and peroxymonosulfate(PMS)-loaded hollow manganese dioxide(HMn)nanoparticles for not only TME-response drug release but also the distinct ROS donors to strengthen CDT.Upon enriched in the tumor site,the prepared nanotheranostic agent(HA@HMn/PMS)depleted local GSH to reduce MnO_(2) to Mn^(2+),followed by generating•OH andSO_(4)^(−)through Fenton-like reaction and activation of PMS,respectively.The bring in of•SO_(4)^(−),a rare radical possessing exceptional oxidizing ability and oxygen-independent property,breaks the limitations of traditional ROS and causes serious damage to tumor cells.In a xenograft mouse tumor model,detailed studies demonstrated that HA@HMn/PMS can significantly inhibit tumor growth.This work inspires the enormous potential of CDT in investigating the application of multifunctional nanosystems by combining the consumption of GSH and the synergistic effect of multiple radicals in oncotherapy.展开更多
Metal ions trigger Fenton/Fenton-like reactions,generating highly toxic hydroxyl radicals(•OH)for chemodynamic therapy(CDT),which is crucial in inducing lethal oxidative DNA damage and subsequent cell apoptosis.Howeve...Metal ions trigger Fenton/Fenton-like reactions,generating highly toxic hydroxyl radicals(•OH)for chemodynamic therapy(CDT),which is crucial in inducing lethal oxidative DNA damage and subsequent cell apoptosis.However,tumor cells can counteract this damage through repair pathways,particularly MutT homolog 1(MTH1)protein attenuation of oxidative DNA damage.Suppression of MTH1 can enhance CDT efficacy,therefore,orderly integrating Fenton/Fenton-like agents with an MTH1 inhibitor is expected to significantly augment CDT effectiveness.Carrier-free CuTH@CD,self-assembled through the supramolecular orchestration ofγ-cyclodextrin(γ-CD)with Cu^(2+)and the MTH1 inhibitor TH588,effectively overcoming tumor resistance by greatly amplifying oxidative damage capability.Without additional carriers and mediated by multiple supramolecular regulatory effects,CuTH@CD enables high drug loading content,stability,and uniform size distribution.Upon internalization by tumor cells,CuTH@CD invalidates repair pathways through Cu^(2+)-mediated glutathione(GSH)depletion and TH588-mediated MTH1 inhibition.Meanwhile,both generated Cu^(+)ions and existing ones within the nanoassembly initiate a Fentonlike reaction,leading to the accumulation of•OH.This strategy enhances CDT efficiency with minimal side effects,improving oxidative damage potency and advancing self-delivery nanoplatforms for developing effective chemodynamic tumor therapies.展开更多
The treatment of multidrug-resistant bacteria is a difficult problem in clinical practice. These drug-resistant bacteria have reduced sensitivity to antibiotics, which contributes to the high incidence and mortality o...The treatment of multidrug-resistant bacteria is a difficult problem in clinical practice. These drug-resistant bacteria have reduced sensitivity to antibiotics, which contributes to the high incidence and mortality of bacterial infections worldwide. Photothermal therapy and chemodynamic therapy are advanced nanomaterial-based medical treatment methods and are widely used in tumor and antibacterial therapies due to their precision and rapidity. To overcome the limitations of conventional treatment for bacterial resistance, this study developed a near-infrared-Ⅱ(NIR-Ⅱ) responsive nanomaterial, a gold nanoframework coated with copper selenide(GNF@CS). This nanomaterial simultaneously triggers both chemodynamic therapy and photothermal therapy, while further promoting the chemodynamic process through in-situ heat generation. Ultimately, it shows significant antibacterial effects against both Staphylococcus aureus and Escherichia coli, providing a new nonantibiotic-dependent treatment strategy for clinically relevant bacterial infections.展开更多
基金supported by the National Key Research and Development Program of China(No.2022YFA1207600)the National Natural Science Foundation of China(Nos.62375289,62175262)+2 种基金the Science and Technology Innovation Program of Hunan Province(No.2022RC1201)the Scientific Research Fund of Hunan Provincial Education Department(No.22B0081)Postdoctoral Funding Project of Jiangsu Province(No.2019Z156)。
文摘Designing and synthesizing nanomedicines with multi-modal tumor therapeutic capabilities is the key to cancer treatment.Herein,we prepared MICG nanoparticles(NPs)by assembling glucose oxidase(GOx)and indocyanine green(ICG)with manganese carbonate(MnCO_(3))NPs for starvation therapy cascaded chemodynamic therapy,enhanced phototherapy and immune activation.In MICG NPs,the GOx consumes intratumoral glucose resulting in starvation therapy,and simultaneously produces H_(2)O_(2)and decreases p H in tumor.The intensified acidic tumor environment promotes the decomposition of MnCO_(3)NPs to release Mn^(2+).The Mn^(2+)further catalyzes H_(2)O_(2)to generate hydroxyl radical for chemodynamic therapy.While ICG can generate singlet oxygen(^(1)O_(2))and heat to kill cancer cells through phototherapy mechanism.The hydroxyl radical and ^(1)O_(2) will further accelerate the oxidative stress,intensify immunogenic cell death,induce dendritic cell maturation,and thus activate systemic immunity.This work provides a new therapeutic platform for combining therapy of tumor.
基金supported by the National Natural Science Foundation of China(Nos.T2293753,52203194)the National Key R&D Program of China(No.2021YFA1201200)+1 种基金the Natural Science Foundation of Zhejiang Province(No.LR18E030002)2023 Hangzhou West Lake Pearl Project Leading Innovative Youth Team Project.
文摘Chemodynamic therapy(CDT),using Fenton agents to generate highly cytotoxic•OH from H_(2)O_(2)has been demonstrated as a powerful anticancer method.However,the insufficient endogenous H_(2)O_(2)in tumor cells greatly limited its therapeutic effect.Herein,we prepared a pH-responsiveβ-lapachone-loaded ironpolyphenol nanocomplex(LIPN)through a one-pot method.β-Lapachone in LIPN selectively enhanced H_(2)O_(2)concentration in tumor cells,and ferrous ions cascadely generated abundant cytotoxic•OH.Therefore,LIPN with cascade amplification of reactive oxygen species(ROS)showed high chemodynamic cytotoxicity in tumor cells,efficiently improving the expression of damage-associated molecular patterns(DAMPs),and exerting strong immunogenic cell death(ICD).As a result,LIPN exhibited efficient tumor inhibition ability in 4T1 subcutaneous tumor model in vivo with great biocompatibility.Additionally,the infiltration of cytotoxic CD8^(+)T lymphocytes and inhibition of regulatory CD4^(+)FoxP3^(+)T lymphocytes in tumors demonstrated the activation of immunosuppressive tumor microenvironment by LIPN-induced ICD.Therefore,this work provided a new approach to enhance ICD of chemodynamic therapy through selective cascade amplification of ROS in cancer cells.
基金supported by the project of the National Key Research and Development Program of China(No.2022YFA1207600)the National Natural Science Foundation of China(Nos.62005294,62375272)TIPC Director’s Fund.
文摘The complexity of cancer therapy has led to the emergence of combination therapy as a promising approach to enhance treatment efficacy and safety.The integration of glutathione(GSH)-activatable two-photon photodynamic therapy(TP-PDT)and chemodynamic therapy(CDT)offers the possibility to advance precision and efficacy in anti-cancer treatments.In this study,a GSH-activatable photosensitizer(PS),namely copper-elsinochrome(CuEC),is synthesized and utilized for combination second nearinfrared(NIR-II)TP-PDT/CDT.The Cu^(2+)acts as a“lock”,suppressing the fluorescence and^(1)O_(2)generation ability of EC in a normal physiological environment(“OFF”state).However,the overexpressed GSH in the tumor microenvironment acts as the“key”,resulting in the release of EC(“ON”state)and Cu^(+)(reduced by GSH).The released EC can be utilized for fluorescence imaging and TP-PDT under NIR-II(λ=1000 nm)two-photon excitation,while Cu+can generate highly toxic hydroxyl radicals(•OH)via Fenton-like reaction for CDT.Additionally,this process consumes GSH and diminishes the tumor’s antioxidant capacity,thereby augmenting the efficacy of combination therapy.The CuEC achieves significant tumor cell ablation in both 2D monolayer cells and 3D multicellular tumor spheres through the combination of NIR-II TP-PDT and CDT.
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financially supported by the National Key Research and Development Program of China(No.2022YFB3503700)the National Natural Science Foundation of China(NSFC,Nos.51929201,52102354,and 52202353)the projects for science and technology development plan of Jilin province(Nos.20220101070JC,20210402046GH,and 20220508089RC)。
文摘Chemodynamic therapy(CDT)relying on the transformation of endogenous hydrogen peroxide(H_(2)O_(2))into cytotoxic hydroxyl radicals(·OH)based on the catalysis of Fenton/Fenton-type reactions exhibits great potentiality for cancer treatment.However,the inadequate H_(2)O_(2)supply and intricate redox homeostasis in tumor microenvironment(TME)severely impair the efficacy of CDT.Herein,we design selfassembled 1,2-distearoyl-sn-glycero-3-phosphoethanolamine conjugated polyethylene glycol(DSPE-PEG)-modified Fe(Ⅲ)-juglone nanoscale coordination polymers(FJP NCPs)as redox homeostasis disruptors for juglone-enhanced CDT.Responding to glutathione(GSH)-rich and acidic TME,the Fe^(2+)/Fe^(3+)-guided CDT and GSH consumption by Fe^(3+)are activated,resulting in·OH downstream and up-regulation of lipid peroxidation(LPO).In addition,the released juglone not only depletes GSH through Michael addition,but also elevates intracellular H_(2)O_(2)level for achieving·OH further bursting.With the impressive efficiency of GSH exhaustion and reactive oxygen species(ROS)storm generation,ferroptosis and apoptosis are significantly enhanced by FJP NCPs in vivo.In brief,this facile and efficient design for versatile nanoscale coordination polymers presents a novel paradigm for effectively elevating CDT efficiency and tumor synergistic therapy.
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(No.82272847,82202318,82304417,82303529)The Henan Province Fund for Cultivating Advantageous Disciplines(No.222301420012)+2 种基金Central Plains science and technology innovation leading talent project(No.234200510005)The project tackling of key scientific and technical problems of Henan Provine(No.232102311163)China Postdoctoral Science Foundation(2022TQ0310,2023TQ0307,2023M730971)。
文摘Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting cancer.However,the potential application of bacterial therapy is hindered by the presence of instability and susceptibility to infections within bacterial populations.Furthermore,monotherapy is ineffective in completely eliminating complex cancer with multiple contributing factors.In this study,based on our discovery that spore shell(SS)of Bacillus coagulans exhibits excellent tumor-targeting ability and adjuvant activity,we develop a biomimetic spore nanoplatform to boost bacteria-mediated antitumor therapy,chemodynamic therapy and antitumor immunity for synergistic cancer treatment.In detail,SS is separated from probiotic spores and then attached to the surface of liposome(Lipo)that was loaded with hemoglobin(Hb),glucose oxidase(GOx)and JQ1to construct SS@Lipo/Hb/GOx/JQ1.In tumor tissue,highly toxic hydroxyl radicals(·OH)are generated via sequential catalytic reactions:GOx catalyzing glucose into H_(2)O_(2)and Fe^(2+)in Hb decomposing H_(2)O_(2)into·OH.The combination of·OH and SS adjuvant can improve tumor immunogenicity and activate immune system.Meanwhile,JQ1-mediated down-regulation of PD-L1 and Hb-induced hypoxia alleviation synergistically reshape immunosuppressive tumor microenvironment and potentiate immune response.In this manner,SS@Lipo/Hb/GOx/JQ1 significantly suppresses tumor growth and metastasis.To summarize,the nanoplatform represents an optimum strategy to potentiate bacteria-based cancer immunotherapy.
基金supported by the National Natural Science Foundation of China(No.62071413)the Hebei Natural Science Foundation of China(Nos.C2019203556 and F2020203056)the Natural Science Foundation of Hebei Province for Innovation Group Project,China(No.C2022203003)。
文摘Photodynamic therapy(PDT)has significant advantages in treating primary tumors.However,the hypoxic tumor microenvironment hinders the generation of sufficient reactive oxygen species during PDT to effectively kill tumor cells,further greatly limiting the applications of PDT in cancer treatment.Herein,we reported a temperature/pH dual controlled drug delivery system LPC@PCN@PDA/Fe^(3+)-AS1411 based on a porous coordination network(PCN(Mn))coated with polydopamine(PDA)and modified with an aptamer AS1411.β-lapachone(LPC)was loaded inside the PCN(Mn)framework,and Fe^(3+)was attached to the surface of the PDA coating.These nanoparticles(NPs)exhibited excellent multimodal cancer therapeutic effects and tumor targeting ability with their photo-and chemodynamic properties.The therapeutic effect can be enhanced by the production of sufficient oxygen by the internal hydrogen peroxide,which improves the photodynamic effect of the photosensitizer PCN(Mn)and the chemotherapy effect ofβ-lapachone.Notably,the conversion of Fe^(2+)to Fe^(3+)in the tumor cells exerts the Fenton effect,which generates hydroxyl radicals that cause lipid peroxidation in tumor cells and induce apoptosis,thus enhancing the chemodynamic therapeutic effect.In vitro and in vivo experiments revealed that the NPs demonstrated specific tumor targeting,excellent inhibition effect on tumor growth,and biocompatibility.Together,our findings can help develop an intelligent multifunctional therapeutic nanoplatform for cancer therapy.
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 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,hostvip 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-vip 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funded by the National Natural Science Foundation of China(Nos.52372264,32271609and 52473109)+2 种基金The Natural Science Foundation of Heilongjiang Province of China(No.LH2023B002)The Fundamental Research Funds for the Central Universities(No.2572023CT12)Undergraduate Training Programs for Innovations by NEFU(No.202310225565)。
文摘Metal-organic frameworks(MOFs)with high porosity,specific surface area,and unique topologies are highly regarded for their applications in photocatalysis,medical treatment,and environmental pollutant degradation.However,due to the limitations of the tumor microenvironment(TME),traditional MOFs have limited efficacy in this environment.This paper designs multi-metal oxide-based heterostructure POMOFs nanoreactors with a nesting doll-like structure.This new structure not only exhibits therapeutic effects in TME but also utilizes ultrasound(US)to enhance the release of reactive oxygen species(ROS)for CDT&SDT co-therapy,becoming an effective sound sensitizer for destroying tumor cells.In summary,our study proposes an idea for constructing multi-metal oxide-based heterostructure MOFs nanoreactors material with a nesting doll-like structure to enhance ROS release and synergistically treat tumor diseases.
文摘An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(Ce6)and triethoxy(1H,1H,2H,2H‑nonafluorohexyl)silane(TFS)was coated on the outer layer of UC,and then a layer of HKUST‑1 shell was coated.The obtained nanocomposite UC@Ce6/TFS@mSiO_(2)@HKUST‑1(noted as UCTSH)was used for the synergistic treatment of chemodynamic therapy(CDT)and photodynamic therapy(PDT).Interestingly,the nanostructures can specifically re lease Cu^(2+)in the acidic tumor microenvironment.Cu^(2+)reacts with excess hydrogen peroxide(H_(2)O_(2))in the tumor microenvironment to form cytotoxic hydroxyl radical.Secondly,Ce6,with the action of oxygen‑carrying TFS,selectively produces a large amount of singlet oxygen by 808 nm laser irradiation.UCTSH can enhance the anti‑tumor effects of PDT and CDT by increasing the production level of reactive oxygen species,without causing damage to normal cells.
基金supported by the Beijing Natural Science Foundation(L248075)the National Natural Science Foundation of China(32171370)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(2022A1515140073 and 2022A1515010415)the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(CI2023C012YL)the Science and Technology Program of Guangzhou(2023A03J0493).
文摘Hepatocellular carcinoma(HCC)is the most common primary liver cancer with a poor prognosis.Chemotherapy is one of the first-line clinical therapeutic strategies for HCC.Still,the effectiveness of chemotherapy is hampered by the tumor immunosuppressive microenvironment and drug resistance caused by insufficient delivery.Herein,we developed a metal-drug self-delivery nanomedicine(FDAH)to improve the chemo/chemodynamic therapeutic efficacy of HCC.The core of FDAH is an iron-based nanoparticle chelated with two clinical drugs,Doxorubicin(DOX)and Plerixafor(AMD3100).Additionally,the nanomedicine is externally modified with a hyaluronic acid(HA)shell,which can prolong the circulation time of the nanoparticles in the bloodstream after intravenous administration.After entering the bloodstream,the nanomedicine reaches the tumor tissue through the EPR effect and is phagocytosed by the tumor cells via HA/CD44-specific interaction.Iron ion-mediated chemodynamic therapy is mediated by the Fenton reaction to generate ROS,causing an imbalance of redox homeostasis within the tumor cells and enhancing the sensitivity of tumor cells to DOX.In addition,AMD3100 intervenes in the CXCL12/CXCR4 axis to influence the infiltration level of immune cells and promote DOX chemotherapy in tumor cells.This work suggests that alleviating immunosuppression via a metal-drug self-delivery system of the CXCR4 inhibitor can effectively improve the DOX chemotherapy and iron ions-mediated chemodynamic therapy.
基金National Natural Science Foundation of China(32301105)Open Project Funding of the State Key Laboratory of Biocatalysis and Enzyme Engineering(SKLBEE20230020)。
文摘The inherent tumor microenvironment(TME)of hypoxia and high glutathione(GSH)hinders the production of reactive oxygen species(ROS),yet which are crucial roles to make the oxygen-independent chemodynamic therapy(CDT)outstanding.Herein,we constructed hyaluronic acid(HA)-modified and peroxymonosulfate(PMS)-loaded hollow manganese dioxide(HMn)nanoparticles for not only TME-response drug release but also the distinct ROS donors to strengthen CDT.Upon enriched in the tumor site,the prepared nanotheranostic agent(HA@HMn/PMS)depleted local GSH to reduce MnO_(2) to Mn^(2+),followed by generating•OH andSO_(4)^(−)through Fenton-like reaction and activation of PMS,respectively.The bring in of•SO_(4)^(−),a rare radical possessing exceptional oxidizing ability and oxygen-independent property,breaks the limitations of traditional ROS and causes serious damage to tumor cells.In a xenograft mouse tumor model,detailed studies demonstrated that HA@HMn/PMS can significantly inhibit tumor growth.This work inspires the enormous potential of CDT in investigating the application of multifunctional nanosystems by combining the consumption of GSH and the synergistic effect of multiple radicals in oncotherapy.
基金funded by Tongzhou District Health Development Research Reserve Project Foundation(No.KJ2024CX024)Natural Science Foundation of Tianjin City(No.23JCQNJC01640)+1 种基金National Natural Science Foundation of China(Nos.82304393,22404122)Beijing Nova Program(No.Z211100002121127).
文摘Metal ions trigger Fenton/Fenton-like reactions,generating highly toxic hydroxyl radicals(•OH)for chemodynamic therapy(CDT),which is crucial in inducing lethal oxidative DNA damage and subsequent cell apoptosis.However,tumor cells can counteract this damage through repair pathways,particularly MutT homolog 1(MTH1)protein attenuation of oxidative DNA damage.Suppression of MTH1 can enhance CDT efficacy,therefore,orderly integrating Fenton/Fenton-like agents with an MTH1 inhibitor is expected to significantly augment CDT effectiveness.Carrier-free CuTH@CD,self-assembled through the supramolecular orchestration ofγ-cyclodextrin(γ-CD)with Cu^(2+)and the MTH1 inhibitor TH588,effectively overcoming tumor resistance by greatly amplifying oxidative damage capability.Without additional carriers and mediated by multiple supramolecular regulatory effects,CuTH@CD enables high drug loading content,stability,and uniform size distribution.Upon internalization by tumor cells,CuTH@CD invalidates repair pathways through Cu^(2+)-mediated glutathione(GSH)depletion and TH588-mediated MTH1 inhibition.Meanwhile,both generated Cu^(+)ions and existing ones within the nanoassembly initiate a Fentonlike reaction,leading to the accumulation of•OH.This strategy enhances CDT efficiency with minimal side effects,improving oxidative damage potency and advancing self-delivery nanoplatforms for developing effective chemodynamic tumor therapies.
文摘The treatment of multidrug-resistant bacteria is a difficult problem in clinical practice. These drug-resistant bacteria have reduced sensitivity to antibiotics, which contributes to the high incidence and mortality of bacterial infections worldwide. Photothermal therapy and chemodynamic therapy are advanced nanomaterial-based medical treatment methods and are widely used in tumor and antibacterial therapies due to their precision and rapidity. To overcome the limitations of conventional treatment for bacterial resistance, this study developed a near-infrared-Ⅱ(NIR-Ⅱ) responsive nanomaterial, a gold nanoframework coated with copper selenide(GNF@CS). This nanomaterial simultaneously triggers both chemodynamic therapy and photothermal therapy, while further promoting the chemodynamic process through in-situ heat generation. Ultimately, it shows significant antibacterial effects against both Staphylococcus aureus and Escherichia coli, providing a new nonantibiotic-dependent treatment strategy for clinically relevant bacterial infections.
