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
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
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
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
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
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
Colorectal cancer is a common cancer worldwide.Traditional chemotherapeutic drugs often face limitations such as poor aqueous solubility and high systemic toxicity,which can lead to adverse side effects and limited th...Colorectal cancer is a common cancer worldwide.Traditional chemotherapeutic drugs often face limitations such as poor aqueous solubility and high systemic toxicity,which can lead to adverse side effects and limited therapeutic efficacy.In this study,a library of one kind of biodegradable and biocompatible polymer,leucine based-poly(ester amide)s(Leu-PEAs)was developed and utilized as drug carrier.The structure of Leu-PEAs can be tuned to alter their physicochemical properties,enhancing drug loading capacity and delivery efficiency.Leu-PEAs can self-assemble into nanoparticles by nanoprecipitation and load paclitaxel(PTX)with the diameter of~108 nm and PTX loading capacity of~8.5%.PTX-loaded Leu-PEAs nanoparticles(PTX@Leu-PEAs)demonstrated significant inhibition of CT26 cell growth in vitro.In vivo,these nanoparticles exhibited prolonged tumor accumulation and antitumor effects,with no observed toxicity to normal organs.Furthermore,blank Leu-PEAs nanoparticles also showed antitumor effects in vitro and in vivo,which may be attributed to the activation of the mammalian target of rapamycin(m TOR)pathway by leucine.Consequently,this biocompatible Leu-PEAs nano-drug delivery system shows potential as a promising strategy for colorectal cancer treatment,warranting further investigation.展开更多
Interactions of hepatic macrophages with local inflammatory microenvironment is the key factor promoting the development of acute liver failure(ALF).Hence,reprogramming pro-inflammatory M1 into anti-inflammatory M2 ph...Interactions of hepatic macrophages with local inflammatory microenvironment is the key factor promoting the development of acute liver failure(ALF).Hence,reprogramming pro-inflammatory M1 into anti-inflammatory M2 phenotype may offer a promising strategy for treating ALF by targeting inflammation.Our group found Carvedilol possessed potential anti-inflammatory property previously,which had been scarcely reported in ALF.We present a synergy strategy to induce macrophages into the phenotype M2-type anti-inflammatory macrophages with interleukin-4(IL-4)and IL-10 at first.Then Carvedilol is loaded on the macrophage membrane-camouflaged biomimetic nano-platform(termed as M2M@CNP)to evade reticuloendothelial system(RES)and afford Carvedilol delivery to the inflammatory environment with overproduced reactive oxygen species(ROS),further prolonging its circulation and accumulation.Sustainably released Carvedilol produced anti-inflammatory,antioxidant and anti-apoptosis effects,combining local M2-type cell membranes(M2-CM)inhibited pro-inflammatory cytokines and ROS levels,which in turn promoted and amplified M1 to M2 phenotype polarization efficiency.This study offers new insights into the rational design of biomimetic nanosystems for safe and effective ALF therapy to accelerate the clinical translation.展开更多
Currently three major problems seriously limit the practical application of can-cer photodynamic therapy(PDT):(i)the hypoxic tumor microenvironment(TME);(ii)low generation efficiency of toxic reactive oxygen species(RO...Currently three major problems seriously limit the practical application of can-cer photodynamic therapy(PDT):(i)the hypoxic tumor microenvironment(TME);(ii)low generation efficiency of toxic reactive oxygen species(ROS)in aggre-gates and(iii)shallow tissue penetration depth of excitation light.Very limited approaches are available for addressing all the above three problems with a single design.Herein,a rational“three birds with one stone”molecular and nanoengi-neering strategy is demonstrated:a photodynamic nanoplatform U-Ir@PAA-ABS based on the covalent combination of lanthanide-doped upconversion nanoparti-cles(UCNPs)and an AIE-active dinuclear Ir(III)complex provides a low oxygen concentration-dependent type-I photochemical process upon 980 nm irradiation by Föster resonance energy transfer(FRET).U-Ir@PAA-ABS targets mitochondria and has excellent phototoxicity even in severe hypoxia environments upon 980 nm irradiation,inducing a dual-mode cell death mechanism by apoptosis and ferropto-sis.Taken together,the in vitro and in vivo results demonstrate a successful strategy for improving the efficacy of PDT against hypoxic tumors.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
The vulnerable plaques in atherosclerosis can cause severe outcome with great danger of acute cardiovascular events.Thus,timely diagnosis and treatment of vulnerable plaques in early stage can effectively benefit the ...The vulnerable plaques in atherosclerosis can cause severe outcome with great danger of acute cardiovascular events.Thus,timely diagnosis and treatment of vulnerable plaques in early stage can effectively benefit the clinical management of atherosclerosis.In this work,a targeting theranostic strategy on early-stage vulnerable plaques in atherosclerosis is realized by a LAID nanoplatform with X-CT and fluorescent dual-mode imaging and lipid-inflammation integrated regulation abilities.The iodinated contrast agents(ICA),phenylboronic acid modified astaxanthin and oxidized-dextran(oxDEX)jointly construct the nanoparticles loaded with the lipid-specific probe LFP.LAID indicates an active targeting to plaques along with the dual-responsive disassembly in oxidative stress and acidic microenvironment of atherosclerosis.The X-CT signals of ICA execute the location of early-stage plaques,while the LFP combines with lipid cores and realizes the recognition of vulnerable plaques.Meanwhile,the treatment based on astaxanthin is performed for restraining the progression of plaques.Transcriptome sequencing suggests that LAID can inhibit the lipid uptake and block NF-κB pathway,which synergistically demonstrates a lipid-inflammation integrated regulation to suppression the plaques growing.The in vivo investigations suggest that LAID delivers a favorable theranostics to the early-stage vulnerable plaques,which provides an impressive prospect for reducing the adverse prognosis of atherosclerosis.展开更多
Combination immunotherapy has shown promising potential for enhancing the objective response rate compared to immune checkpoint blockade(ICB)monotherapy.However,combination therapy with multi-drugs is limited by the d...Combination immunotherapy has shown promising potential for enhancing the objective response rate compared to immune checkpoint blockade(ICB)monotherapy.However,combination therapy with multi-drugs is limited by the different properties of the agents and inconsistent synergistic targeted delivery.Herein,based on a universal triterpene template and the anticancer active agent ursolic acid(UA),a cytomembrane-coated biomimetic delivery nanoplatform(UR@M)prepared by the selfassembly of a PD-L1 targeted CRISPR/Cas9 system and UA was designed for hepatocellular carcinoma(HCC)treatment.UR@M showed enhanced tumor accumulation in vivo with homologous tumor targeting,and CRISPR in the nanosystem exhibited potent gene-editing efficiency of 76.53% in vitro and 62.42% in vivo with no off-target effects.UA activated the natural immune system through the TLR-2-MyD88-TRAF6 pathway,which synergistically enhanced the proliferation of natural killer cells and dendritic cells and realized excellent immune cytotoxic T cell infiltration by combining with the ICB of PD-L1.The strategy of work along both lines based on innate immune and adaptive immunity displayed a significant effect in tumor regression.Overall,the UA-templated strategy“killed three birds with one stone”by establishing a self-assembly nanosystem,inducing tumor cell death,and promoting synergistic immunostimulation for HCC treatment.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
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
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
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
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
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
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 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support of the National Natural Science Foundation of China(Nos.52173150,52073313)the Guangzhou Science and Technology Program City-University Joint Funding Project(No.2023A03J0001)the Shenzhen Science and Technology Program(No.KCXFZ 202002011010232)。
文摘Colorectal cancer is a common cancer worldwide.Traditional chemotherapeutic drugs often face limitations such as poor aqueous solubility and high systemic toxicity,which can lead to adverse side effects and limited therapeutic efficacy.In this study,a library of one kind of biodegradable and biocompatible polymer,leucine based-poly(ester amide)s(Leu-PEAs)was developed and utilized as drug carrier.The structure of Leu-PEAs can be tuned to alter their physicochemical properties,enhancing drug loading capacity and delivery efficiency.Leu-PEAs can self-assemble into nanoparticles by nanoprecipitation and load paclitaxel(PTX)with the diameter of~108 nm and PTX loading capacity of~8.5%.PTX-loaded Leu-PEAs nanoparticles(PTX@Leu-PEAs)demonstrated significant inhibition of CT26 cell growth in vitro.In vivo,these nanoparticles exhibited prolonged tumor accumulation and antitumor effects,with no observed toxicity to normal organs.Furthermore,blank Leu-PEAs nanoparticles also showed antitumor effects in vitro and in vivo,which may be attributed to the activation of the mammalian target of rapamycin(m TOR)pathway by leucine.Consequently,this biocompatible Leu-PEAs nano-drug delivery system shows potential as a promising strategy for colorectal cancer treatment,warranting further investigation.
基金supported by grants from the Research Unit Project of Chinese Academy of Medical Sciences(No.2019-I2M-5-030)the Research Project of Jinan Microecological Biomedicine Shandong Laboratory(No.JNL-2022002A)the Zhejiang Provincial Natural Science Foundation of China(No.LQ22H030009).
文摘Interactions of hepatic macrophages with local inflammatory microenvironment is the key factor promoting the development of acute liver failure(ALF).Hence,reprogramming pro-inflammatory M1 into anti-inflammatory M2 phenotype may offer a promising strategy for treating ALF by targeting inflammation.Our group found Carvedilol possessed potential anti-inflammatory property previously,which had been scarcely reported in ALF.We present a synergy strategy to induce macrophages into the phenotype M2-type anti-inflammatory macrophages with interleukin-4(IL-4)and IL-10 at first.Then Carvedilol is loaded on the macrophage membrane-camouflaged biomimetic nano-platform(termed as M2M@CNP)to evade reticuloendothelial system(RES)and afford Carvedilol delivery to the inflammatory environment with overproduced reactive oxygen species(ROS),further prolonging its circulation and accumulation.Sustainably released Carvedilol produced anti-inflammatory,antioxidant and anti-apoptosis effects,combining local M2-type cell membranes(M2-CM)inhibited pro-inflammatory cytokines and ROS levels,which in turn promoted and amplified M1 to M2 phenotype polarization efficiency.This study offers new insights into the rational design of biomimetic nanosystems for safe and effective ALF therapy to accelerate the clinical translation.
基金NSFC,Grant/Award Numbers:52073045,51773195Key Scientific and Technological Project of Jilin Province,Grant/Award Number:20190701010GH+2 种基金Development and Reform Commission of Jilin Province,Grant/Award Number:2020C035-5Changchun Science and Technology Bureau,Grant/Award Number:21ZGY19EPSRC,Grant/Award Number:EP/L02621X/1。
文摘Currently three major problems seriously limit the practical application of can-cer photodynamic therapy(PDT):(i)the hypoxic tumor microenvironment(TME);(ii)low generation efficiency of toxic reactive oxygen species(ROS)in aggre-gates and(iii)shallow tissue penetration depth of excitation light.Very limited approaches are available for addressing all the above three problems with a single design.Herein,a rational“three birds with one stone”molecular and nanoengi-neering strategy is demonstrated:a photodynamic nanoplatform U-Ir@PAA-ABS based on the covalent combination of lanthanide-doped upconversion nanoparti-cles(UCNPs)and an AIE-active dinuclear Ir(III)complex provides a low oxygen concentration-dependent type-I photochemical process upon 980 nm irradiation by Föster resonance energy transfer(FRET).U-Ir@PAA-ABS targets mitochondria and has excellent phototoxicity even in severe hypoxia environments upon 980 nm irradiation,inducing a dual-mode cell death mechanism by apoptosis and ferropto-sis.Taken together,the in vitro and in vivo results demonstrate a successful strategy for improving the efficacy of PDT against hypoxic tumors.
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supported by National Natural Science Foundation of China (No.32201128,No.82270262,and No.82070408)Zhejiang TCM Science and Technology Program TCM modernization Special project,China (No.2022ZX012).
文摘The vulnerable plaques in atherosclerosis can cause severe outcome with great danger of acute cardiovascular events.Thus,timely diagnosis and treatment of vulnerable plaques in early stage can effectively benefit the clinical management of atherosclerosis.In this work,a targeting theranostic strategy on early-stage vulnerable plaques in atherosclerosis is realized by a LAID nanoplatform with X-CT and fluorescent dual-mode imaging and lipid-inflammation integrated regulation abilities.The iodinated contrast agents(ICA),phenylboronic acid modified astaxanthin and oxidized-dextran(oxDEX)jointly construct the nanoparticles loaded with the lipid-specific probe LFP.LAID indicates an active targeting to plaques along with the dual-responsive disassembly in oxidative stress and acidic microenvironment of atherosclerosis.The X-CT signals of ICA execute the location of early-stage plaques,while the LFP combines with lipid cores and realizes the recognition of vulnerable plaques.Meanwhile,the treatment based on astaxanthin is performed for restraining the progression of plaques.Transcriptome sequencing suggests that LAID can inhibit the lipid uptake and block NF-κB pathway,which synergistically demonstrates a lipid-inflammation integrated regulation to suppression the plaques growing.The in vivo investigations suggest that LAID delivers a favorable theranostics to the early-stage vulnerable plaques,which provides an impressive prospect for reducing the adverse prognosis of atherosclerosis.
基金supported by the National Natural Science Foundation of China(No.82172767)the External Cooperation Research Programs of Science and Technology Department Foundation of Fujian Province,China(No.2023I0038).
文摘Combination immunotherapy has shown promising potential for enhancing the objective response rate compared to immune checkpoint blockade(ICB)monotherapy.However,combination therapy with multi-drugs is limited by the different properties of the agents and inconsistent synergistic targeted delivery.Herein,based on a universal triterpene template and the anticancer active agent ursolic acid(UA),a cytomembrane-coated biomimetic delivery nanoplatform(UR@M)prepared by the selfassembly of a PD-L1 targeted CRISPR/Cas9 system and UA was designed for hepatocellular carcinoma(HCC)treatment.UR@M showed enhanced tumor accumulation in vivo with homologous tumor targeting,and CRISPR in the nanosystem exhibited potent gene-editing efficiency of 76.53% in vitro and 62.42% in vivo with no off-target effects.UA activated the natural immune system through the TLR-2-MyD88-TRAF6 pathway,which synergistically enhanced the proliferation of natural killer cells and dendritic cells and realized excellent immune cytotoxic T cell infiltration by combining with the ICB of PD-L1.The strategy of work along both lines based on innate immune and adaptive immunity displayed a significant effect in tumor regression.Overall,the UA-templated strategy“killed three birds with one stone”by establishing a self-assembly nanosystem,inducing tumor cell death,and promoting synergistic immunostimulation for HCC treatment.
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.
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 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.
