A biomimetic spore nanoplatform for boosting chemodynamic therapy and bacteria-mediated antitumor immunity for synergistic cancer treatment

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.

Boosting Chemodynamic Therapy by the Synergistic Effect of Co‑Catalyze and Photothermal Effect Triggered by the Second Near‑Infrared Light

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.

Self-Assembly Protein Superstructures as a Powerful Chemodynamic Therapy Nanoagent for Glioblastoma Treatment

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.

Cytochrome-c aptamer functionalized Pt nanoclusters for enhanced chemodynamic therapy

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.

Valence-tailored copper-based nanoparticles for enhanced chemodynamic therapy through prolonged ROS generation and potentiated GSH depletion

Chemodynamic therapy(CDT),an inventive approach to cancer treatment,exploits innate chemical processes to trigger cell death through the generation of reactive oxygen species(ROS).While offering advantages over conventional treatments,the optimization of CDT efficacy presents challenges stemming from suboptimal catalytic efficiency and the counteractive ROS scavenging effect of intracellular glutathione(GSH).In this study,we aim to address this dual challenge by delving into the role of copper valence states in CDT.Leveraging the unique attributes of copper-based nanoparticles,especially zero-valent copper nanoparticles(CuPd NPs),we aim to enhance the therapeutic potential of CDT.Our experiments reveal that zero-valent CuPd NPs outperform divalent copper nanoparticles(Ox-CuPd NPs)by displaying superior catalytic performance and sustaining ROS generation through a dual approach integrating peroxidase-like(POD-like)activity and Cu+release.Notably,zero-valent NPs exhibit enhanced GSH depletion compared to their divalent counterparts,thereby intensifying CDT and inducing ferroptosis,ultimately resulting in high-efficiency tumor growth inhibition.These findings reveal the impact of valences on CDT,providing novel insights for the optimization and design of CDT agents.

NIR-switchable local hydrogen generation by tandem bimetallic MOFs nanocomposites for enhanced chemodynamic therapy

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.

A Review on Nanomaterial-based Strategies for Manipulating Tumor Microenvironment to Enhance Chemodynamic Therapy

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.

Adenosine triphosphate-responsive carbon dots nanoreactors for T_(1)-weighted magnetic resonance imaging-guided tumor chemodynamic therapy

There are various strategies to conduct tumor microenvironment(TME)stimulus-responsive(e.g.,acid,H_(2)O_(2)or glutathione)nanoreactors for increasing the efficiency of chemodynamic therapy(CDT).Among these,the exploitation of adenosine triphosphate(ATP,another overexpressed biomarker in TME)-responsive nanoreactors for tumor CDT is still challenging.Herein,the ATP-responsive iron-doped CDs(FeCDs)were firstly prepared and then coassembled with glucose oxidase(GOx)to obtain FeCDs/GOx liposomes as ATP-responsive nanoreactors.Under TME conditions,the nanoreactors initially released FeCDs and GOx.Subsequently,with the existence of ATP,iron ions were rapidly released from the FeCDs to trigger Fenton/Fenton-like reactions for generating·OH.Meanwhile,the T_(1)-weighted magnetic resonance imaging(MRI)was achieved due to the released iron ions.Moreover,the GOx converted endogenous glucose in tumor to gluconic acid and H_(2)O_(2)to satisfy the requirement of·OH generation.In vitro as well as in vivo experiments illustrated that the obtained ATP-responsive CD nanoreactors could be used as a versatile nanotheranostics for simultaneously T_(1)-weighted MRI-guided tumor CDT.This work presents a new ATP-responsive nanoreactor with selfsupplied H_(2)O_(2)for multifunctional nanotheranostic applications.

Fe(Ⅲ)-juglone nanoscale coordination polymers for cascade chemodynamic therapy through synergistic ferroptosis and apoptosis strategy

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.

Light/pH dual controlled drug release"nanocontainer"alleviates tumor hypoxia for synergistic enhanced chemotherapy,photodynamic therapy and chemodynamic therapy

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.

Tumor Microenvironment-Adaptive Nanoplatform Synergistically Enhances Cascaded Chemodynamic Therapy

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.

Ferric oxide nanosheet-engineered Mg alloy for synergetic osteosarcoma photothermal/chemodynamic therapy

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.

Mesothelin targeted nano-system enhanced chemodynamic therapy and tirapazamine chemotherapy via lactate depletion

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.

Mesoporous polydopamine delivery system for intelligent drug release and photothermal-enhanced chemodynamic therapy using MnO_(2) as gatekeeper

The non-specific leakage of drugs from nanocarriers seriously weakened the safety and efficacy of chemotherapy,and it was very critical of constructing tumor microenvironment(TME)-responsive delivery nanocarriers,achieving the modulation release of drugs.Herein,using manganese dioxide(MnO_(2))as gatekeeper,an intelligent nanoplatform based on mesoporous polydopamine(MPDA)was developed to deliver doxorubicin(DOX),by which the DOX release was precisely controlled,and simultaneously the photothermal therapy(PTT)and chemodynamic therapy(CDT)were realized.In normal physiological environment,the stable MnO_(2)shell effectively avoided the leakage of DOX.However,in TME,the overexpressed glutathione(GSH)degraded MnO_(2)shell,which caused the DOX release.Moreover,the photothermal effect of MPDA and the Fenton-like reaction of the generated Mn^(2+)further accelerated the cell death.Thus,the developed MPDA-DOX@MnO_(2)nanoplatform can intelligently modulate the release of DOX,and the combined CDT/PTT/chemotherapy possessed high-safety and high-efficacy against tumors.

Copper-mediated chemodynamic therapy with ultra-low copper consumption by doping cupric ion on cross-linked(R)-(+)-lipoic acid nanoparticles

Cu-mediated chemodynamic therapy(CDT)has attracted prominent attention owing to its advantages of pH independence and high efficiency comparing to Fe-mediated CDT,while the application of Cu-based CDT agents was impeded due to the high copper consumption caused by the metabolism loss of copper and the resultant potential toxicity.Herein,we developed a new copper-mediated CDT agent with extremely low Cu usage by anchoring copper on cross-linked lipoic acid nanoparticles(Cu@cLAs).After endocytosis into tumor cells,the Cu@cLAs were dissociated into LA and dihydrolipoic acid(DHLA)(reduced form of LA)and released Cu^(2+)and Cu+(oxidized form of Cu^(2+)),the two redox couples recycled each other in cells to achieve the efficient killing of cancer cells by delaying metabolic loss and increasing the ROS level of tumor cells.The self-recycling was confirmed in cells by the sustained high Cu/DHLA content and persistent ROS generation process.The antitumor study based on the MCF-7/R nude mice gave the Cu@cLAs a tumor inhibitory rate up to 77.9%at the copper of 0.05 mg kg^(−1),the first dosage reported so far lower than that of normal serum copper(0.83±0.21 mg kg^(−1)).This work provides not only a new promising clinical strategy for the copper excessive use in copper-mediated CDT,but also gives a clue for other metal mediated disease therapies with the high metal consumption.

Spatially asymmetric cascade nanocatalysts for enhanced chemodynamic therapy

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.

Silica-based nanoarchitecture for an optimal combination of photothermal and chemodynamic therapy functions of Cu2–xS cores with red emitting carbon dots

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.

Host-guest interactions based supramolecular complexes self-assemblies for amplified chemodynamic therapy with H_(2)O_(2) elevation and GSH consumption properties

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.

Temperature-feedback two-photon-responsive metal-organic frameworks for efficient photothermal therapy

The realization of real-time thermal feedback for monitoring photothermal therapy(PTT)under near-infrared(NIR)light irradiation is of great interest and challenge for antitumor therapy.Herein,by assembling highly efficient photothermal conversion gold nanorods and a temperature-responsive probe((E)-4-(4-(diethylamino)styryl)-1-methylpyridin-1-ium,PyS)within MOF-199,an intelligent nanoplatform(AMPP)was fabricated for simultaneous chemodynamic therapy and NIR light-induced temperature-feedback PTT.The fluorescence intensity and temperature of the PyS probe are linearly related due to the restriction of the rotation of the characteristic monomethine bridge.Moreover,the copper ions resulting from the degradation of MOF-199 in an acidic microenvironment can convert H_(2)O_(2)into•OH,resulting in tumor ablation through a Fenton-like reaction,and this process can be accelerated by increasing the temperature.This study establishes a feasible platform for fabricating highly sensitive temperature sensors for efficient temperature-feedback PTT.

Targeting nanoplatform synergistic glutathione depletion-enhanced chemodynamic,microwave dynamic,and selective-microwave thermal to treat lung cancer bone metastasis

Once bone metastasis occurs in lung cancer,the efficiency of treatment can be greatly reduced.Current mainstream treatments are focused on inhibiting cancer cell growth and preventing bone destruction.Microwave ablation(MWA)has been used to treat bone tumors.However,MWA may damage the surrounding normal tissues.Therefore,it could be beneficial to develop a nanocarrier combined with microwave to treat bone metastasis.Herein,a microwave-responsive nanoplatform(MgFe_(2)O_(4)@ZOL)was constructed.MgFe_(2)O_(4)ZOL NPs release the cargos of Fe^(3+),Mg^(2+)and zoledronic acid(ZOL)in the acidic tumor microenvironment(TME).Fe^(3+)can deplete intracellular glutathione(GSH)and catalyze H_(2)O_(2)to generate•OH,resulting in chemodynamic therapy(CDT).In addition,the microwave can significantly enhance the production of reactive oxygen species(ROS),thereby enabling the effective implementation of microwave dynamic therapy(MDT).Moreover,Mg^(2+)and ZOL promote osteoblast differentiation.In addition,MgFe_(2)O_(4)ZOL NPs could target and selectively heat tumor tissue and enhance the effect of microwave thermal therapy(MTT).Both in vitro and in vivo experiments revealed that synergistic targeting,GSH depletion-enhanced CDT,MDT,and selective MTT exhibited significant antitumor efficacy and bone repair.This multimodal combination therapy provides a promising strategy for the treatment of bone metastasis in lung cancer patients.