Hydrogen sulfide responsive nanoplatforms: Novel gas responsive drug delivery carriers for biomedical applications

Hydrogen sulfide(H_(2)S)is a toxic,essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter.These studies have mainly focused on the production and pharmacological side effects caused by H_(2)S.Therefore,effective strategies to remove H_(2)S has become a key research topic.Furthermore,the development of novel nanoplatforms has provided new tools for the targeted removal of H_(2)S.This paper was performed to review the association between H_(2)S anddisease,relatedH_(2)S inhibitory drugs,aswell as H_(2)S responsive nanoplatforms(HRNs).This review first analyzed the role of H_(2)S in multiple tissues and conditions.Second,common drugs used to eliminate H_(2)S,as well as their potential for combination with anticancer agents,were summarized.Not only the existing studies on HRNs,but also the inhibition H_(2)S combined with different therapeutic methods were both sorted out in this review.Furthermore,this review provided in-depth analysis of the potential of HRNs about treatment or detection in detail.Finally,potential challenges of HRNs were proposed.This study demonstrates the excellent potential of HRNs for biomedical applications.

Oxidation-strengthened disulfide-bridged prodrug nanoplatforms with cascade facilitated drug release for synergetic photochemotherapy

One of the major barriers in utilizing prodrug nanocarriers for cancer therapy is the slow release of parent drug in tumors.Tumor cells generally display the higher oxidative level than normal cells,and also displayed the heterogeneity in terms of redox homeostasis level.We previously found that the disulfide bond-linkage demonstrates surprising oxidationsensitivity to form the hydrophilic sulfoxide and sulphone groups.Herein,we develop oxidation-strengthened prodrug nanosystem loaded with pyropheophorbide a(PPa)to achieve light-activatable cascade drug release and enhance therapeutic efficacy.The disulfide bond-driven prodrug nanosystems not only respond to the redox-heterogeneity in tumor,but also respond to the exogenous oxidant(singlet oxygen)elicited by photosensitizers.Once the prodrug nanoparticles(NPs)are activated under irradiation,they would undergo an oxidative self-strengthened process,resulting in a facilitated drug cascade release.The IC50 value of the PPa@PTX-S-S NPs without irradiation was 2-fold higher than those of NPs plus irradiation.In vivo,the PPa@PTX prodrug NPs display prolonged systemic circulation and increased accumulation in tumor site.The PPa@PTXS-S NPs showed much higher efficiency than free PTX or the PPa@PTX-C-C NPs to suppress the growth of 4 T1 tumors.Therefore,this novel oxidation-strengthened disulfide-bridged prodrug-nanosystem has a great potential in the enhanced efficacy of cancer synergetic photochemotherapy.

Nanoplatforms for Sepsis Management: Rapid Detection/Warning, Pathogen Elimination and Restoring Immune Homeostasis

Sepsis,a highly life-threatening organ dysfunction caused by uncontrollable immune responses to infection,is a leading contributor to mortality in intensive care units.Sepsis-related deaths have been reported to account for 19.7%of all global deaths.However,no effective and specific therapeutic for clinical sepsis management is available due to the complex pathogenesis.Concurrently eliminating infections and restoring immune homeostasis are regarded as the core strategies to manage sepsis.Sophisticated nanoplatforms guided by supramolecular and medicinal chemistry,targeting infection and/or imbalanced immune responses,have emerged as potent tools to combat sepsis by supporting more accurate diagnosis and precision treatment.Nanoplatforms can overcome the barriers faced by clinical strategies,including delayed diagnosis,drug resistance and incapacity to manage immune disorders.Here,we present a comprehensive review highlighting the pathogenetic characteristics of sepsis and future therapeutic concepts,summarizing the progress of these well-designed nanoplatforms in sepsis management and discussing the ongoing challenges and perspectives regarding future potential therapies.Based on these state-of-the-art studies,this review will advance multidisciplinary collaboration and drive clinical translation to remedy sepsis.

Biointerface engineering nanoplatforms for cancer-targeted drug delivery

Over the past decade,nanoparticle-based therapeutic modalities have become promising strategies in cancer therapy.Selective delivery of anticancer drugs to the lesion sites is critical for elimination of the tumor and an improved prognosis.Innovative design and advanced biointerface engineering have promoted the development of various nanocarriers for optimized drug delivery.Keeping in mind the biological framework of the tumormicroenvironment,biomembrane-camouflaged nanoplatforms have been a research focus,reflecting their superiority in cancer targeting.In this review,we summarize the development of various biomimetic cell membrane-camouflaged nanoplatforms for cancertargeted drug delivery,which are classified according to the membranes fromdifferent cells.The challenges and opportunities of the advanced biointerface engineering drug delivery nanosystems in cancer therapy are discussed.

Soft Mesoporous Organosilica Nanoplatforms Improve Blood Circulation,Tumor Accumulation/Penetration,and Photodynamic Efficacy

To date,the ability of nanoplatforms to achieve excellent therapeutic responses is hindered by short blood circulation and limited tumor accumulation/penetration.Herein,a soft mesoporous organosilica nanoplatform modified with hyaluronic acid and cyanine 5.5 are prepared,denoted SMONs-HA-Cy5.5,and comparative studies between SMONs-HA-Cy5.5(24.2 MPa)and stiff counterparts(79.2 MPa)are conducted.Results indicate that,apart from exhibiting a twofold increase in tumor cellular uptake,the soft nanoplatforms also display a remarkable pharmacokinetic advantage,resulting in considerably improved tumor accumulation.Moreover,SMONs-HA-Cy5.5 exhibits a significantly higher tumor penetration,achieving 30-μm deeper tissue permeability in multicellular spheroids relative to the stiff counterparts.Results further reveal that the soft nanoplatforms have an easier extravasation from the tumor vessels,diffuse farther in the dense extracellular matrix,and reach deeper tumor tissues compared to the stiff ones.Specifically,the soft nanoplatforms generate a 16-fold improvement(43 vs.2.72μm)in diffusion distance in tumor parenchyma.Based on the significantly improved blood circulation and tumor accumulation/penetration,a soft therapeutic nanoplatform is constructed by loading photosensitizer chlorin e6 in SMONs-HA-Cy5.5.The resulting nanoplatform exhibits considerably higher therapeutic efficacy on tumors compared to the stiff ones.

Recent deveolpment of multifunctional responsive gas-releasing nanoplatforms for tumor therapeutic application

Gas therapy(GT)exhibits great potential for clinical application due to its high therapeutic efficiency,low systemic side effects,and biosafety,thereinto,a multifunctional nanoplatform is generally needed for controllable gas release and precise delivery to tumor tissue.In this review,the recent development of multifunctional nanoplatforms for efficient tumor delivery of stimuliresponsive gas-releasing molecules(GRMs),which could be triggered by either exogenous physical or endogenous tumor microenvironment(TME)is summarized.The reported therapeutic gas molecules,including oxygen(O_(2)),hydrogen sulfide(H_(2)S),nitric oxide(NO),hydrogen(H_(2)),and carbon monoxide(CO),etc.,could directly influence or change the pathological status.Additionally,abundant nanocarriers have been employed for gas delivery into cancer region,such as mesoporous silica nanoparticles(MSNs),metal-organic frameworks(MOFs),two-dimensional(2D)nanomaterials,and liposomes,as well as nonnanocarriers including inorganic and organic nanoparticles.In the end,the outlooks of current challenges of GT and GRMs delivery nanoplatforms as well as the prospects of future clinical applications are proposed.

Nanotheranostics:A powerful next-generation solution to tackle hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is an epidemic burden and remains highly prevalent worldwide.The significant mortality rates of HCC are largely due to the tendency of late diagnosis and the multifaceted,complex nature of treatment.Meanwhile,current therapeutic modalities such as liver resection and transplantation are only effective for resolving early-stage HCC.Hence,alt-ernative approaches are required to improve detection and enhance the efficacy of current treatment options.Nanotheranostic platforms,which utilize biocompatible nanoparticles to perform both diagnostics and targeted delivery,has been considered a potential approach for cancer management in the past few decades.Advancement of nanomaterials and biomedical engineering techniques has led to rapid expansion of the nanotheranostics field,allowing for more sensitive and specific diagnosis,real-time monitoring of drug delivery,and enhanced treatment efficacies across various malignancies.The focus of this review is on the applications of nanotheranostics for HCC.The review first explores the current epidemiology and the commonly encountered obstacles in HCC diagnosis and treatment.It then presents the current technological and functional advancements in nanotheranostic technology for cancer in general,and then specifically explores the use of nanotheranostic modalities as a promising option to address the key challenges present in HCC management.

A coating strategy on titanium implants with enhanced photodynamic therapy and CO-based gas therapy for bacterial killing and inflammation regulation

Antimicrobial photodynamic therapy(aPDT)has been considered a noninvasive and effective modality against the bacterial infection of peri‑implantitis,especially the aPDT triggered by near-infrared(NIR)light due to the large penetration depth in tissue.However,the complexity of hypoxia microenvironments and the distance of aPDT sterilization still pose challenges before realizing the aPDT clinical application.Due to the long lifespan and transmission distance of therapeutic gas molecules,we design a multi-functional gas generator that combines aPDT as well as O_(2) and CO gas release function,which can solve the problem of hypoxia(O_(2))in PDT and the problem of inflammation regulation(CO)in the distal part of peri‑implant inflammation under near-infrared(NIR)irradiation.In the composite nanoplatform that spin-coated on the surface of titanium implants,up-conversion nanoparticles(UCNPs)were involved in converting the NIR to visible,which further excites the partially oxidized stannic sulfide(SnS_(2)),realizing the therapeutic gas release.Indocyanine green(ICG)was further integrated to enhance the aPDT performance(Ti-U@SnS_(2)/I).Therefore,reactive oxygen species(ROS),CO,and O_(2) can be controllably administered via a composite nano-platform mediated by a single NIR light(808 nm).This implant surface modification strategy could achieve great self-enhancement antibacterial effectiveness and regulate the lingering questions,such as relieving the anoxic microenvironment and reaching deep infection sites,providing a viable antibiotic-free technique to combat peri‑implantitis.

Nanodrug enhances post-ablation immunotherapy of hepatocellular carcinoma via promoting dendritic cell maturation and antigen presentation

Thermal ablation(TA)as an effective method treating hepatocellular carcinoma(HCC)in clinics is facing great challenges of high recurrence and metastasis.Although immune-checkpoint blockade(ICB)-based immuno-therapy has shown potential to inhibit recurrence and metastasis,the combination strategy of ICB and thermal ablation has shown little progress in HCC treatments.The tremendous hurdle for combining ICB with thermal ablation lies with the insufficient antigen internalization and immaturity of tumor-infiltrating dendritic cells(TIDCs)which leads to an inferior immune response to distant tumor growth and metastasis.Herein,an antigen-capturing nanoplatform,whose surface was modified with mannose as a targeting ligand,was constructed for co-delivering tumor-associated antigens(TAAs)and m6A demethylases inhibitor(i.e.,fat mass and obesity asso-ciated gene(FTO)inhibitor)into TIDCs.In vivo results demonstrate that the intratumoral injection of nanodrug followed by HCC thermal ablation promotes dendritic cells(DCs)maturation,improves tumor infiltration of effector T cells and generates immune memory,which synergize with ICB treatment to inhibit the distant tumor growth and lung metastasis.Therefore,the antigen-capturing and FTO-inhibiting nanodrug holds potential to boost the ICB-based immunotherapy against HCC after thermal ablation.

Self-oxygenated co-assembled biomimetic nanoplatform for enhanced photodynamic therapy in hypoxic tumor

Photodynamic therapy(PDT)has shown great application potential in cancer treatment and the important manifestation of PDT in the inhibition of tumors is the activation of immunogenic cell death(ICD)effects.However,the strategy is limited in the innate hypoxic tumor microenvironment.There are two key elements for the realization of enhanced PDT:specific cellular uptake and release of the photosensitizer in the tumor,and a sufficient amount of oxygen to ensure photodynamic efficiency.Herein,self-oxygenated biomimetic nanoparticles(CS@M NPs)co-assembled by photosensitizer prodrug(Ce6-S-S-LA)and squalene(SQ)were engineered.In the treatment of triple negative breast cancer(TNBC),the oxygen carried by SQ can be converted to reactive oxygen species(ROS).Meanwhile,glutathione(GSH)consumption during transformation from Ce6-S-S-LA to chlorin e6(Ce6)avoided the depletion of ROS.The co-assembled(CS NPs)were encapsulated by homologous tumor cell membrane to improve the tumor targeting.The results showed that the ICD effect of CS@M NPs was confirmed by the significant release of calreticulin(CRT)and high mobility group protein B1(HMGB1),and it significantly activated the immune system by inhibiting the hypoxia inducible factor-1alpha(HIF-1α)-CD39-CD73-adenosine a2a receptor(A2AR)pathway,which not only promoted the maturation of dendritic cells(DC)and the presentation of tumor specific antigens,but also induced effective immune infiltration of tumors.Overall,the integrated nanoplatform implements the concept of multiple advantages of tumor targeting,reactive drug release,and synergistic photodynamic therapy-immunotherapy,which can achieve nearly 90%tumor suppression rate in orthotopic TNBC models.

Ofloxacin loaded M0S2 nanoflakes for synergistic mild-temperature photothermal/antibiotic therapy with reduced drug resistance of bacteria

Antibiotic resistance is an increasingly serious threat to global public health, which can lead to the decrease of the effectiveness ofantibiotics. The combination therapy of antibiotic and mild temperature photothermal therapy (PTT) is adopted to address this issue inthis work. An antibiotic-loaded nanoplatform is fabricated based on two-dimensional (2D) molybdenum disulfide (M0S2) nanoflakesas effective near-infrared (NIR) photothermal agent. The M0S2 nanoflakes is modified with positively charged quaternized chitosan(QCS) to improve the dispersion stability and enhance the interaction between M0S2 nanoflakes and bacterial membrane. TheQCS modified M0S2 nanoflakes (QCS-M0S2) is expected to adhere onto the membrane of methicillin-resistant Staphylococcusaureus (MRSA) and depolarize the bacterial membrane by local hyperthermia under NIR irradiation. A first-line antibiotic, ofloxacin(OFLX), can be loaded onto QCS-M0S2 by π-π stacking and hydrophobic interaction. Due to the combined antibiotic-photothermaltherapy, superior bactericidal ability was achieved at mild temperature (45℃) and low antibiotic concentration. Such synergisticmild-temperature photothermal/antibiotic therapy can not only avoid the damage to neighboring tissue by PTT, but also reduce thedevelopment of drug resistance, providing an innovative way for the treatment of bacterial infections.

Transformative hyaluronic acid-based active targeting supramolecular nanoplatform improves long circulation and enhances cellular uptake in cancer therapy

Hyaluronic acid(HA) is a natural ligand of tumor-targeted drug delivery systems(DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors(HARE and LYVE-1) are also overexpressing in the reticuloendothelial system(RES). Therefore,polyethylene glycol(PEG) modification of HA-based DDS is necessary to reduce RES capture.Unfortunately, pegylation remarkably inhibits tumor cellular uptake and endosomal escapement,significantly compromising the in vivo antitumor efficacy. Herein, we developed a Dox-loaded HA-based transformable supramolecular nanoplatform(Dox/HCVBP) to overcome this dilemma. Dox/HCVBP contains a tumor extracellular acidity-sensitive detachable PEG shell achieved by a benzoic imine linkage.The in vitro and in vivo investigations further demonstrated that Dox/HCVBP could be in a "stealth" state at blood stream for a long circulation time due to the buried HA ligands and the minimized nonspecific interaction by PEG shell. However, it could transform into a "recognition" state under the tumor acidic microenvironment for efficient tumor cellular uptake due to the direct exposure of active targeting ligand HA following PEG shell detachment. Such a transformative concept provides a promising strategy to resolve the dilemma of natural ligand-based DDS with conflicting two processes of tumor cellular uptake and in vivo nonspecific biodistribution.

NIR light-induced tumor phototherapy using ICG delivery system based on platelet-membrane-camouflaged hollow bismuth selenide nanoparticles

Near-infrared(NIR)light-triggered photothermal therapy(PTT)is a promising treatment strategy for treating cancer.The combination of nanotechnology and NIR has been widely applied.However,the therapeutic efficacy of the drug-delivery system depends on their ability to avoid phagocytosis of endothelial system,cross the biological barriers,prolong circulation life,localize and rapidly release the therapeutic at target sites.In this work,we designed a platelet membrane(PM)-camouflaged hollow mesoporous bismuth selenide nanoparticles(BS NPs)loading with indocyanine green(ICG)(PM@BS-ICG NPs)to achieve the above advantages.PM-coating has active tumor-targe ting ability which could preve nt drug leakage and provide drug long circulation,causing drug delivery systems to accumulate in tumor sites effectively.Moreover,as a type of the photothermal sensitizers,BS NPs are used as the inner cores to improve ICG stability and are served as scaffolds to enhance the hardness of this drug delivery system.For one hand,the thermal vibration of BS NPs under NIR laser irradiation causes tumor inhibition through hyperthermia.For another hand,this hyperthermia process could damage PM and let ICG rapid release from PM@BS-ICG NPs.The in vitro and in vivo results showed that this biomimetic nano-drug delivery system exhibits obvious antitumor activity which has good application prospect.

ICG@ZIF-8:One-step encapsulation of indocyanine green in ZIF-8 and use as a therapeutic nanoplatform

How to fabricate zeolitic imidazole framework-8 （ZIF-8） based therapeutic nanoplatform will be of significance in biomedicine considering its good biocompatibility. Herein, we report a one-step encapsulation of indocyanine green （ICG） in ZlF-8 nanoparticles （NPs）. The as-prepared ICG@ZIF-8 NPs possess an absorption band in the near infrared region and have the good photothermal conversion efficiency. The in vivo and in vitro studies show that, after loading chemotherapy agent hydrophobic doxorubicin （DOX）, ICG@ZIF-8-DOX NPs exhibit the chem-and photothermal synergistic therapy for tumor. In addition, it is found that the embedded ICG molecules in ICG@ZlF-8 NPs can be disassociated and released into the solution upon the 808 nm laser irradiation, demonstrating that as-prepared ICG@ZIF-8 NPs can also be used as the optical imaging probe to trace the degradability behavior of resulting NPs in future

A novel clustered SPIO nanoplatform with enhanced magnetic resonance T2 relaxation rate for micro-tumor detection and photothermal synergistic therapy

Construction of micro tumor sensitive theranostic nanoagents that can increase the accuracy of imaging diagnosis and boost the therapeutic efficacy has been demonstrated for a promising approach for diagnosis and treatment of cancer.Herein,we reported a novel super-paramagnetic iron oxide(SPIO)based nanoplatform that possess significantly enhanced magnetic resonance property and photothermal effect for tumor theranostic purpose.This polyethylene glycol with four phenylboronic acid(PEG-B4)/CNTs@porphyrin(ph)/SPIO(BCPS)nanoplatform was simply prepared via integrated SPIO,ph,and a novel dendrimer with PEG liner and four PBA groups(PEG-B4)on the surface of carbon nanotubes(CNTs).Subsequently,a significant T2 relaxation rate enhanced can be achieved by the reduced accessibility of water to SPIO clustering.Moreover,the synergetic enhanced photothermal from BCPS nanoplatform contributed to better photothermal effect for cancer therapy.Furthermore,the targeting ability to sialic acid overexpressed tumor was further introduced from phenylboronic acid from PEG-B4.We showed that BCPS nanoplatform could not only selectively identify solid tumors and detect micro-sized metastatic tumor(1 mm)in the liver,but also effectively ablate tumors in a xenograft model,thereby achieving a complete cure rate of 100%at low laser dose.Our results highlight the potential of BCPS nanoplatform for accurate micro-tumor diagnosis and effective tumor therapy.

Chain-shattering Pt(IV)-backboned polymeric nanoplatform for efficient CRISPR/Cas9 gene editing to enhance synergistic cancer therapy

CRISPR/Cas9 system has become a promising gene editing tool for cancer treatment.However,development of a simple and effective nanocarrier to incorporate CRISPR/Cas9 system and chemotherapeutic drugs to concurrently tackle the biological safety and packaging capacity of viral vectors and combine gene editing-chemo for cancer therapy still remains challenges.Herein,a chain-shattering Pt(IV)-backboned polymeric nanoplatform is developed for the delivery of EZH2-targeted CRISPR/Cas9 system(NPCSPt/pEZH2)and synergistic treatment of prostate cancer.The pEZH2/Pt(II)could be effectively triggered to unpack/release from NPCSPt/pEZH2 in a chain-shattering manner in cancer cells.The EZH2 gene disruption efficiency could be achieved up to 32.2%of PC-3 cells in vitro and 21.3%of tumor tissues in vivo,leading to effective suppression of EZH2 protein expression.Moreover,significant H3K27me3 downregulation could occur after EZH2 suppression,resulting in a more permissive chromatin structure that increases the accessibility of released Pt(II)to nuclear DNA for enhanced apoptosis.Taken together,substantial proliferation inhibition of prostate cancer cells and further 85.4%growth repression against subcutaneous xenograft tumor could be achieved.This chain-shattering Pt(IV)-backboned polymeric nanoplatform system not only provides a prospective nanocarrier for CRISPR/Cas9 system delivery,but also broadens the potential of combining gene editing-chemo synergistic cancer therapy.

Liposome-based multifunctional nanoplatform as effective therapeutics for the treatment of retinoblastoma

Photothermal therapy has the characteristics of minimal invasiveness,controllability,high efficiency,and strong specificity,which can effectively make up for the toxic side effects and tumor resistance caused by traditional drug treatment.However,due to the limited tissue penetration of infrared light,it is difficult to promote and apply in clinical practice.The eye is the only transparent tissue in human,and infrared light can easily penetrate the eye tissue,so it is expected that photothermal therapy can be used to treat fundus diseases.Here in,a new nano-platform assembled by liposome and indocyanine green(ICG) was used to treat retinoblastoma.ICG was assembled in liposomes to overcome some problems of ICG itself.For example,ICG is easily quenched,self-aggregating and instability.Moreover,liposomes can prevent free ICG from being cleared through the systemic circulation.The construction of the nano-platform not only ensured the stability of ICG in vivo,but also realized imaging-guide photothermal therapy,which created a new strategy for the treatment of retinoblastoma.

Fabrication of a Magnetite Nanoparticle-loaded Polymeric Nanoplatform for Magnetically Guided Drug Delivery

We developed a magnetite nanoparticle-loaded polymeric nanoplatform for magnetically guided 10- hydroxycamptothecin（HCPT） delivery. The nanoplatform was fabricated by simultaneously incorporating magnetite nanoparticles（NPs） and HCPT into the polymer micelle self-assembled from methoxy polyethylene glycolpoly（D,L-lactide-co-glycolide）（MPEG-PLGA） copolymer. Successful loading of HCPT into the nanoplatform was confirmed by Fourier transform infrared（FTIR） spectroscopy. Subsequently, we examined the in vitro antitumor efficacy of free HCPT and nanoplatform against three different cancer cell lines HeLa, A549 and HepG2. Flow cytometric analysis was condkt ,ucted to reveal the cell apoptosis caused by free HCPT and nanoplatform. Finally, the magnetic targeting property of the nanoplatform was evaluated by a self-designed in vitro experiment.

Folate-targeted co-delivery polymersomes for efficient photo-chemo-antiangiogenic therapy against breast cancer and in vivo evaluation via OCTA/NIRF dual-modal imaging

Intelligent nanoplatform that combines multimodal imaging and therapeutic effects holds great promise for precise and efficient cancer therapy.Herein,folate-targeted polymersomes with stimuli-responsiveness were fabricated and evaluated by near-infrared fluorescence(NIRF)and optical coherence tomography angiography(OCTA)dual-imaging for photo-chemo-antiangiogenic therapy against cancer.The folate-targeted polymersomes(FA-MIT-SIPS)not only integrated ammonium bicarbonate(ABC)and mitoxantrone(MIT)into their hydrophilic cavity but also encapsulated indocyanine green(ICG)and sorafenib(SOR)within their hydrophobic layer.NIRF imaging demonstrated that FA-MIT-SIPS effectively accumulated and retained in the tumors.Upon 808 nm laser irradiation,the ICG produced hyperthermia and reactive oxygen species(ROS)for efficient photothermal and photodynamic therapy.In addition,the decomposition of ABC in responsive to acidic tumor environment and ICG-induced hyperthermia accelerated drug release.The released MIT accumulated in nucleus to inhibit DNA synthesis,while the released SOR destructed tumor vascularization.Notably,OCTA imaging was applied to observe the tumor blood flow upon the combination therapy,demonstrating that FA-MIT-SIPS obviously decreased the vessels area density.Moreover,the synergistic photo-chemo-antiangiogenic therapy of FA-MIT-SIPS achieved excellent antitumor effect with 40%of the 4T1 tumor-bearing mice being completely cured without recurrence.The multifunctional polymersomes provide a promising dual-modal imaging-evaluated synergistic strategy for tumor therapy.

Copper-thioguanine metallodrug with self-reinforcing circular catalysis for activatable MRI imaging and amplifying specificity of cancer therapy

For chemotherapy, drug delivery systems often suffer from the inefficient drug loading capability, which usually cause systems toxicity and extra burden to excrete carrier itself. Moreover, the cancer therapeutic efficacy is also greatly limited by the specificity of tumor microenvironment for reactive oxygen species(ROS) based cancer therapeutic strategy(e.g., chemodynamic therapy). Herein, we have developed metal-drug coordination nanoplatform that can not only be responsive to tumor microenvironment but also modulate it, so as to achieve efficient treatment of cancer. Excitingly, by employing small molecule drug(6-thioguanine) as ligand copper ions, we achieve a high drug loading rate(60.1%) and 100% of utilization of metal-drug coordination nanoplatform(Cu-TG). Interestingly, Cu-TG possessed high-efficiently horseradish peroxidase-like, glutathione peroxidase-like and catalase-like activity. Under the tumor microenvironment, Cu-TG exhibited the self-reinforcing circular catalysis that is able to amplify the cellular oxidative stress, inducing notable cancer cellular apoptosis. Moreover, Cu-TG could be activated with glutathione(GSH) and facilitated for GSH triggered 6-TG release, higher selective therapeutic effect toward cancer cells, and GSH activated T1 weight-magnetic resonance imaging. Based on the above properties, Cu-TG exhibited magnetic resonance imaging(MRI) guiding, efficient and synergistic combination of chemodynamic and chemotherapy with self-reinforcing therapeutic outcomes in vivo.