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 focus...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.展开更多
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...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.展开更多
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 accou...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.展开更多
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...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.展开更多
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 modi...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.展开更多
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 controll...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.展开更多
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...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.展开更多
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 ...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.展开更多
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 ha...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.展开更多
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...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.展开更多
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 phototherm...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.展开更多
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 overe...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.展开更多
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 th...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.展开更多
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 indo...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展开更多
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 trea...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.展开更多
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 t...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.展开更多
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 tradi...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.展开更多
We developed a magnetite nanoparticle-loaded polymeric nanoplatform for magnetically guided 10- hydroxycamptothecin(HCPT) delivery. The nanoplatform was fabricated by simultaneously incorporating magnetite nanoparti...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.展开更多
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 fabri...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.展开更多
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 effi...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.展开更多
基金supported by National Key Research and Development Program of China(contract No.2019YFA0904800)National Nature Science Foundation of China(32030065,31722033,92049304 to Y.Z.)+5 种基金Shanghai Sailing Program(contract No.21YF1410300)Science and Technology Commission of Shanghai Municipality(contract No.10DZ2220500)The Shanghai Committee of Science and Technology(grant No.11DZ2260600)Shanghai Frontiers Science Center of Optogenetic Techniques for CellMetabolism(Y.Z.)Research Unit of New Techniques for Live-cell Metabolic Imaging(Chinese Academy of Medical Sciences,2019-I2M-5-013 to Y.Z.)the State Key Laboratory of Bioreactor Engineering,the Fundamental Research Funds for the Central Universities.
文摘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.
基金financially supported by National Nature Science Foundation of China(No.81872816,81703451)Liaoning Revitalization Talents Program,No XLYC1808017+2 种基金Key projects of Technology bureau in Shenyang,No18400408Key projects of Liaoning Province Department of Education,No.2017LZD03supported by Heilongjiang Provincial Key Laboratory of Plant Genetic Engineering and Biological Fermentation Engineering for Cold Region。
文摘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.
基金the National Key Research and Development Program of China(Grant No.2018YFC2001904).
文摘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.
基金Financially supported by the National Natural Science Foundation of China(Grant Nos.51973216,51873207,51803006,51673190,51603204,51673187,and 51520105004)the Science and Technology Development Program of Jilin Province(Grant Nos.20190201068JC,20170101102JC,and 20160414047GH)+2 种基金the Medical and Health Program of Jilin Province(Grant No.20190304047YY)the Youth Talents Promotion Project of Jilin Province(Grant No.181909)and the Youth Innovation Promotion Association of Chinese Academy of Sciences(Grant No.2019005).
文摘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.
基金supported by National Key Basic Research Program of China(973 Program),China(2014CB744504)the National Natural Science Foundation of China,China(81971675,21603106 and 81971681)the Natural Science Foundation of Jiangsu Province,China(BK20160017)。
文摘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.
基金supported by the National Key R&D Program of China(No.2021YFB3801001)the National Natural Science Foundation of China(Nos.32030061 and 81720108023)the Key Program for Basic Research of Shanghai(Nos.19JC1415600 and 21JC1406000).
文摘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.
文摘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.
基金the National Natural Science Foundation of China(Nos.82170998,82201102,62205122)the Postdoctoral Science Foundation Project of China(No.2022M721316)+4 种基金the General program of the Natural Science Foundation of Jilin Province(Nos.YDZJ202201ZYTS017,20220203145SF,20210203087SF,YDZJ202201ZYTS274,YDZJ202201ZYTS080)Hygiene and Health Appropriate Technology Promotion Project of Jilin Province(No.2020S014)the Science and Technology Project of Jilin Province Financial Department(Nos.jcsz202189321,jcsz2021893-15,Zkjc D105181350043103358)Science and Technology Project of Jilin Province Education Department(No.JJKH20221098KJ)the Health Department Research Projects of Jilin Province(No.2022JC076)for financial support.
文摘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.
基金National Natural Science Foundation of China(51933011,31971296,52173125,82102194,81873920,82001930)Key Areas Research and Development Program of Guangzhou(202007020006)+2 种基金Natural Science Foundation of the Guangdong Province(2021A1515010250,2020A1515111206,2021A1515111006)China Postdoctoral Science Foundation(2020M680119,2021M703763)Funding of the Southern Medical University Nanfang Hospital(2019C015).
文摘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.
基金supported by the Guangdong Nature Resource Center(No.(2020)037)Natural Science Foundation of Guangdong Province(Nos.22019A1515011498 and 2019A1515011619)+2 种基金Basic and Applied Basic Research Foundation of Guangdong Province(No.2020B1515120063)National Natural Science Foundation of China(No.81803877)supported by the China Postdoctoral Science Foundation(No.2022M721535)。
文摘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.
基金Financial support from the National Natural Science Foundation of China(No.21774110)Fundamental Research Funds for the Central Universities(Nos.2019QNA4063 and 2019XZZX005-1-03)is gratefully acknowledged.
文摘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.
基金supported by the National Basic Research Program of China(No.81573371)the Key Projects of Liaoning Province Department of Education(No.2017LZD03,China)
文摘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.
基金supported by the National Natural Science Foundation of China(Nos.81673021 and U1804183)the Scientific and Technological Project of Henan Province(No.182102310117)。
文摘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.
基金financially supported by the State Key Basic Research Program of the PRC(No.2014CB744501)the NSF of China(No.81771976)+1 种基金Fundamental Research Funds for the Central Universitiesthe joint fund of Southeast University and Nanjing Medical University
文摘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
基金This work was supported by National Natural Science Foundation of China(No.81971664)Shanghai Pujang Program(2019PJD044)+1 种基金National Key Research and Development Project of China(2016YFB0303200)Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support.
文摘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.
基金The authors acknowledge the financial support from National Natural Science Foundation of China(Grant Nos.51773198,51673188,and 21975246)The animal study protocol was approved by the Institutional Animal Care and Use Committee at Chinese Academy of Sciences.
文摘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.
基金financially supported by National Natural Science Foundation of China(7212092,81770887)China Postdoctoral Science Foundation(2019M650558)+1 种基金Beijing Postdoctoral Research FoundationBeijing Chaoyang District Postdoctoral Research Foundation。
文摘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.
基金Supported by the National Natural Science Foundation of China(Nos.30970719, 81000669), the Social Development Project of the Science and Technology Department of Jilin Province, China(No.20106031), the Project of Science and Technology Department of Changchun City, China(No.2009080-09SF02), the Specialized Research Fund for the Doctoral Program of Higher Education of China(No.20100061120077) and the China Postdoctoral Science Foundation(No.20100481048).
文摘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.
基金supported by the National Natural Science Foundation of China(Nos.82072059 and 82172090)the Fundamental Research Funds for the Central Universities(No.2019PT320028)+2 种基金Tianjin Municipal Natural Science Foundation(No.20JCYBJC00030)CAMS Initiative for Innovative Medicine(No.2021-I2M-1-058)Science and Technology Planning Project of Tianjin(No.18ZXSGSY00050).
文摘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.
基金supported by the National Natural Science Foundation of China (51872088, 21977027, 21804039, 21675043, 21890744)。
文摘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.