Dimeric prodrug nanoassemblies(DPNAs)offer great potential in improving the efficacy of chemotherapy.Previously,we developed tetrasulfide bonds as a novel response module and the obtainedγ-4S-2CTX NPs demonstrated su...Dimeric prodrug nanoassemblies(DPNAs)offer great potential in improving the efficacy of chemotherapy.Previously,we developed tetrasulfide bonds as a novel response module and the obtainedγ-4S-2CTX NPs demonstrated superlative self-assembly stability and enhanced anti-tumor efficacy.However,current DPNAs mainly rely on simple PEGylation for surface modification to improve blood circulation,which lacks tumor-selective functionality and limits their further application.To address these limitations,we introduced a new surface modification strategy using RM-1 tumor cell membranes(CMs)to enhance biofunctionality.The initial attempt to use CMs as a single surface modification failed because the affinity of nanocores-CMs remains a problem,which affected the stability of membrane-coated DPNAs.To address this,we used 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N[methoxy(polyethyleneglycol)-2000](DSPE-PEG2k)as an adhesive bridge to improve the affinity between CMs and DPNAs,resulting in a dual-modified formulation termed CM-pDPNAs.This dual modification strategy enhanced CMs binding to DPNAs,enabling precise tumor recognition and internalization,thereby improving tumor elimination efficacy.Furthermore,this approach addressed key challenges associated with current CM-coated nanoparticles(CM-NPs),including complex preparation procedures and poor drug-carrier compatibility.This work elucidates the application of CMs as surface modification modules,paving the way for the next generation of biomimetic prodrug nanoassemblies with superior stability and tumor specficity.展开更多
Glioblastoma multiforme(GBM)is a highly aggressive and lethal brain tumor with limited treatment options.To improve therapeutic efficacy,we developed a novel multifunctional nanoplatform,GM@P(T/S),comprised of polymer...Glioblastoma multiforme(GBM)is a highly aggressive and lethal brain tumor with limited treatment options.To improve therapeutic efficacy,we developed a novel multifunctional nanoplatform,GM@P(T/S),comprised of polymeric nanoparticles coated with GBM cell membranes as well as co-loaded with temozolomide(TMZ)and superparamagnetic iron oxide(SPIO)nanoparticles.The successful preparation was confirmed in terms of particle size,morphology,stability,the in vitro drug release,and cellular uptake assays.We demonstrated that GM@P(T/S)exhibited the enhanced homotypic targeting,the prolonged blood circulation,and efficient bloodbrain barrier penetration in both in vitro and in vivo studies.The combination of TMZ and SPIO nanoparticles within GM@P(T/S)synergistically improved chemo-radiation therapy,leading to a reduced tumor growth,an increased survival,and minimal systemic toxicity in the orthotopic GBM mouse models.Our findings suggest that GM@P(T/S)holds a great promise as a targeted and efficient therapeutic strategy for GBM.展开更多
Drug therapy towards tumours often causes adverse effects because of their non-specific nature.Membrane-coated technology and membrane-coated nanoparticles provide an advanced and promising platform of targeted and sa...Drug therapy towards tumours often causes adverse effects because of their non-specific nature.Membrane-coated technology and membrane-coated nanoparticles provide an advanced and promising platform of targeted and safe delivery.By camouflaging the nanoparticles with natural derived or artificially modified cell membranes,the nano-payloads are bestowed with properties from cell membranes such as longer circulation,tumour or inflammation-targeting,immune stimulation,augmenting the performance of traditional therapeutics.In this review,we review the development of membrane coating technology,and summarise the technical details,physicochemical properties,and research status of membrane-coated nanoparticles from different sources in tumour treatment.Finally,we also look forward to the prospects and challenges of transforming membrane coating technology from experiment into clinical use.Taken together,membrane-coated nanoparticles are bound to become one of the most potential anti-tumour strategies in the future.展开更多
The healing of diabetic wounds is primarily hindered by persistent inflammation and excessive oxidative stress,increasing the risks of amputation and sepsis.Strategies based on bioactive substances,including recombina...The healing of diabetic wounds is primarily hindered by persistent inflammation and excessive oxidative stress,increasing the risks of amputation and sepsis.Strategies based on bioactive substances,including recombinant growth factors and histatin proteins(Hsts),have been shown to promote skin-related cell migration,anti-inflammation,angiogenesis,and collagen deposition;however,their long-term stability remains a challenge.Herein,a platelet membrane-coated nanoparticle(PNP)system is proposed to achieve enhanced retention of aggregation-induced emissive(AIE)molecular-modified Hst1(Hst1-AIE@PNPs)for more efficient repair of diabetic wounds.The Hst1-AIE@PNPs can not only protect Hst1 from degradation in the wound microenvironment but also permit visual monitoring of the controlled release of Hst1 through enhanced fluorescence in the enriched site.Combined with the antioxidant and anti-inflammatory properties of Hst1,Hst1-AIE@PNPs can effectively adsorb inflammation-related factors and further promote re-epithelialization and collagen deposition,thus achieving high-quality wound repair.The results highlight the potential of highly stable aggregation-induced-emissionfunctionalized Hst1 coated with platelet vesicles as a therapeutic platform to promote diabetic wound-related tissue restoration processes.展开更多
Background:Immunosuppressive M2 macrophages in the tumor microenvironment(TME)can mediate the therapeutic resistance of tumors,and seriously affect the clinical efficacy and prognosis of tumor patients.This study aims...Background:Immunosuppressive M2 macrophages in the tumor microenvironment(TME)can mediate the therapeutic resistance of tumors,and seriously affect the clinical efficacy and prognosis of tumor patients.This study aims to develop a novel drug delivery system for dual-targeting tumor and macrophages to inhibit tumor and induce macrophage polarization.Methods:The anti-tumor effects of methyltransferase like 14(METTL14)were investigated both in vitro and in vivo.The underlying mechanisms of METTL14 regulating macrophages were also explored in this study.We further constructed the cyclic(Arg-Gly-Asp)(cRGD)peptide modified macrophage membrane-coated nanovesicles to co-deliver METTL14 and the TLR4 agonist.Results:We found that METTL14 significantly inhibits the growth of tumor in vitro.METTL14 might downregulate TICAM2 and inhibit the Toll-like receptor 4(TLR4)pathway of macrophages,meanwhile,the combination of METTL14 and the TLR4 agonist could induce M1 polarization of macrophages.Macrophage membrane-coated nanovesicles are characterized by easy modification,drug loading,and dual-targeting tumor and macrophages,and cRGD modification can further enhance its targeting ability.It showed that the nanovesicles could improve the in vivo stability of METTL14,and dual-target tumor and macrophages to inhibit tumor and induce M1 polarization of macrophages.Conclusions:This study anticipates achieving the dual purposes of tumor inhibition and macrophage polarization,and providing a new therapeutic strategy for tumors.展开更多
Sustained and intense inflammation is the pathological basis for intervertebral disc degeneration(IVDD).Effective antagonism or reduction of local inflammatory factors may help regulate the IVDD microenvironment and r...Sustained and intense inflammation is the pathological basis for intervertebral disc degeneration(IVDD).Effective antagonism or reduction of local inflammatory factors may help regulate the IVDD microenvironment and reshape the extracellular matrix of the disc.This study reports an immunomodulatory hydrogel microsphere system combining cell membrane-coated mimic technology and surface chemical modification methods by grafting neutrophil membrane-coated polylactic-glycolic acid copolymer nanoparticles loaded with transforming growth factor-beta 1(TGF-β1)(T-NNPs)onto the surface of methacrylic acid gelatin anhydride microspheres(GM)via amide bonds.The nanoparticle-microsphere complex(GM@T-NNPs)sustained the long-term release of T-NNPs with excellent cell-like functions,effectively bound to pro-inflammatory cytokines,and improved the release kinetics of TGF-β1,maintaining a 36 day-acting release.GM@T-NNPs significantly inhibited lipopolysaccharide-induced inflammation in nucleus pulposus cells in vitro,downregulated the expression of inflammatory factors and matrix metalloproteinase,and upregulated the expression of collagen-II and aggrecan.GM@T-NNPs effectively restored intervertebral disc height and significantly improved the structure and biomechanical function of the nucleus pulposus in a rat IVDD model.The integration of biomimetic technology and nano-drug delivery systems expands the application of biomimetic cell membrane-coated materials and provides a new treatment strategy for IVDD.展开更多
Given their dangerous effects on the nervous system,neurotoxins represent a significant threat to public health.Various therapeutic approaches,including chelating agents,receptor decoys,and toxin-neutralizing antibodi...Given their dangerous effects on the nervous system,neurotoxins represent a significant threat to public health.Various therapeutic approaches,including chelating agents,receptor decoys,and toxin-neutralizing antibodies,have been explored.While prophylactic vaccines are desirable,it is oftentimes difficult to effectively balance their safety and efficacy given the highly dangerous nature of neurotoxins.To address this,we report here on a nanovaccine against neurotoxins that leverages the detoxifying properties of cell membrane-coated nanoparticles.A genetically modified cell line with constitutive overexpression of theα7 nicotinic acetylcholine receptor is developed as a membrane source to generate biomimetic nanoparticles that can effectively and irreversibly bind toα-bungarotoxin,a model neurotoxin.This abrogates the biological activity of the toxin,enabling the resulting nanotoxoid to be safely delivered into the body and processed by the immune system.When co-administered with an immunological adjuvant,a strong humoral response againstα-bungarotoxin is generated that protects vaccinated mice against a lethal dose of the toxin.Overall,this work highlights the potential of using genetic modification strategies to develop nanotoxoid formulations against various biological threats.展开更多
Atherosclerosis(AS)has emerged as one of the prevalent arterial vascular diseases characterized by plaque and inflammation,primarily causing disability and mortality globally.Drug therapy remains the main treatment fo...Atherosclerosis(AS)has emerged as one of the prevalent arterial vascular diseases characterized by plaque and inflammation,primarily causing disability and mortality globally.Drug therapy remains the main treatment for AS.However,a series of obstacles hinder effective drug delivery.Nature,from natural micro-/nano-structural biological particles like natural cells and extracellular vesicles to the distinctions between the normal and pathological microenvironment,offers compelling solutions for efficient drug delivery.Nature-inspired nanocarriers of synthetic stimulus-responsive materials and natural components,such as lipids,proteins and membrane structures,have emerged as promising candidates for fulfilling drug delivery needs.These nanocarriers offer several advantages,including prolonged blood circulation,targeted plaque delivery,targeted specific cells delivery and controlled drug release at the action site.In this review,we discuss the nature-inspired nanocarriers which leverage the natural properties of cells or the microenvironment to improve atherosclerotic drug therapy.Finally,we provide an overview of the challenges and opportunities of applying these innovative nature-inspired nanocarriers.展开更多
Cancer immunotherapy can effectively inhibit cancer progression by activating the autoimmune system, with low toxicity and high effectiveness. Some of cancer immunotherapy had positive effects on clinical cancer treat...Cancer immunotherapy can effectively inhibit cancer progression by activating the autoimmune system, with low toxicity and high effectiveness. Some of cancer immunotherapy had positive effects on clinical cancer treatment. However, cancer immunotherapy is still restricted by cancer heterogeneity, immune cell disability, tumor immunosuppressive microenvironment and systemic immune toxicity. Cell membrane-coated nanoparticles(CMCNs) inherit abundant source cell-relevant functions, including “self” markers, cross-talking with the immune system, biological targeting, and homing to specific regions. These enable them to possess preferred characteristics, including better biological compatibility, weak immunogenicity, immune escaping, a prolonged circulation, and tumor targeting.Therefore, they are applied to precisely deliver drugs and promote the effect of cancer immunotherapy.In the review, we summarize the latest researches of biomimetic CMCNs for cancer immunotherapy,outline the existing specific cancer immune therapies, explore the unique functions and molecular mechanisms of various cell membrane-coated nanoparticles, and analyze the challenges which CMCNs face in clinical translation.展开更多
基金the National Key R&D Program of China(No.2022YFE0111600)the National Natural Science Foundation of China(No.82204318)+2 种基金Key research and development program of Liaoning Province(No.2024JH2/102500061)Youth innovation team of Liaoning Province Department of Education(No.LJ222410163049)Liaoning Revitalization Talents Program(No.XLYC2203083).
文摘Dimeric prodrug nanoassemblies(DPNAs)offer great potential in improving the efficacy of chemotherapy.Previously,we developed tetrasulfide bonds as a novel response module and the obtainedγ-4S-2CTX NPs demonstrated superlative self-assembly stability and enhanced anti-tumor efficacy.However,current DPNAs mainly rely on simple PEGylation for surface modification to improve blood circulation,which lacks tumor-selective functionality and limits their further application.To address these limitations,we introduced a new surface modification strategy using RM-1 tumor cell membranes(CMs)to enhance biofunctionality.The initial attempt to use CMs as a single surface modification failed because the affinity of nanocores-CMs remains a problem,which affected the stability of membrane-coated DPNAs.To address this,we used 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N[methoxy(polyethyleneglycol)-2000](DSPE-PEG2k)as an adhesive bridge to improve the affinity between CMs and DPNAs,resulting in a dual-modified formulation termed CM-pDPNAs.This dual modification strategy enhanced CMs binding to DPNAs,enabling precise tumor recognition and internalization,thereby improving tumor elimination efficacy.Furthermore,this approach addressed key challenges associated with current CM-coated nanoparticles(CM-NPs),including complex preparation procedures and poor drug-carrier compatibility.This work elucidates the application of CMs as surface modification modules,paving the way for the next generation of biomimetic prodrug nanoassemblies with superior stability and tumor specficity.
基金supported by the National Natural Science Foundation of China(Grant Nos.82073308 and 82104089)。
文摘Glioblastoma multiforme(GBM)is a highly aggressive and lethal brain tumor with limited treatment options.To improve therapeutic efficacy,we developed a novel multifunctional nanoplatform,GM@P(T/S),comprised of polymeric nanoparticles coated with GBM cell membranes as well as co-loaded with temozolomide(TMZ)and superparamagnetic iron oxide(SPIO)nanoparticles.The successful preparation was confirmed in terms of particle size,morphology,stability,the in vitro drug release,and cellular uptake assays.We demonstrated that GM@P(T/S)exhibited the enhanced homotypic targeting,the prolonged blood circulation,and efficient bloodbrain barrier penetration in both in vitro and in vivo studies.The combination of TMZ and SPIO nanoparticles within GM@P(T/S)synergistically improved chemo-radiation therapy,leading to a reduced tumor growth,an increased survival,and minimal systemic toxicity in the orthotopic GBM mouse models.Our findings suggest that GM@P(T/S)holds a great promise as a targeted and efficient therapeutic strategy for GBM.
文摘Drug therapy towards tumours often causes adverse effects because of their non-specific nature.Membrane-coated technology and membrane-coated nanoparticles provide an advanced and promising platform of targeted and safe delivery.By camouflaging the nanoparticles with natural derived or artificially modified cell membranes,the nano-payloads are bestowed with properties from cell membranes such as longer circulation,tumour or inflammation-targeting,immune stimulation,augmenting the performance of traditional therapeutics.In this review,we review the development of membrane coating technology,and summarise the technical details,physicochemical properties,and research status of membrane-coated nanoparticles from different sources in tumour treatment.Finally,we also look forward to the prospects and challenges of transforming membrane coating technology from experiment into clinical use.Taken together,membrane-coated nanoparticles are bound to become one of the most potential anti-tumour strategies in the future.
基金supported by the China Postdoctoral Science Foundation(grant number 2023M731548)the National Natural Science Foundation of China(grant numbers 82322042,82102444)+2 种基金the National Key Research and Development Program of China(grant number 2021YFC2302200)the Natural Science Fund of Guangdong Province for Distinguished Young Scholars(grant number 2022B1515020089)the Basic and Applied Basic Research Project of Guangzhou(grant number SL2023A04J01463).
文摘The healing of diabetic wounds is primarily hindered by persistent inflammation and excessive oxidative stress,increasing the risks of amputation and sepsis.Strategies based on bioactive substances,including recombinant growth factors and histatin proteins(Hsts),have been shown to promote skin-related cell migration,anti-inflammation,angiogenesis,and collagen deposition;however,their long-term stability remains a challenge.Herein,a platelet membrane-coated nanoparticle(PNP)system is proposed to achieve enhanced retention of aggregation-induced emissive(AIE)molecular-modified Hst1(Hst1-AIE@PNPs)for more efficient repair of diabetic wounds.The Hst1-AIE@PNPs can not only protect Hst1 from degradation in the wound microenvironment but also permit visual monitoring of the controlled release of Hst1 through enhanced fluorescence in the enriched site.Combined with the antioxidant and anti-inflammatory properties of Hst1,Hst1-AIE@PNPs can effectively adsorb inflammation-related factors and further promote re-epithelialization and collagen deposition,thus achieving high-quality wound repair.The results highlight the potential of highly stable aggregation-induced-emissionfunctionalized Hst1 coated with platelet vesicles as a therapeutic platform to promote diabetic wound-related tissue restoration processes.
基金This study is supported by the National Natural Science Foundation of China(No.82203059)the China Postdoctoral Science Foundation(2021M701335).
文摘Background:Immunosuppressive M2 macrophages in the tumor microenvironment(TME)can mediate the therapeutic resistance of tumors,and seriously affect the clinical efficacy and prognosis of tumor patients.This study aims to develop a novel drug delivery system for dual-targeting tumor and macrophages to inhibit tumor and induce macrophage polarization.Methods:The anti-tumor effects of methyltransferase like 14(METTL14)were investigated both in vitro and in vivo.The underlying mechanisms of METTL14 regulating macrophages were also explored in this study.We further constructed the cyclic(Arg-Gly-Asp)(cRGD)peptide modified macrophage membrane-coated nanovesicles to co-deliver METTL14 and the TLR4 agonist.Results:We found that METTL14 significantly inhibits the growth of tumor in vitro.METTL14 might downregulate TICAM2 and inhibit the Toll-like receptor 4(TLR4)pathway of macrophages,meanwhile,the combination of METTL14 and the TLR4 agonist could induce M1 polarization of macrophages.Macrophage membrane-coated nanovesicles are characterized by easy modification,drug loading,and dual-targeting tumor and macrophages,and cRGD modification can further enhance its targeting ability.It showed that the nanovesicles could improve the in vivo stability of METTL14,and dual-target tumor and macrophages to inhibit tumor and induce M1 polarization of macrophages.Conclusions:This study anticipates achieving the dual purposes of tumor inhibition and macrophage polarization,and providing a new therapeutic strategy for tumors.
基金supported by the National Natural Science Foundation of China (82072438,82272501,81972078,82120108017,82102589,82372484,82302683)Natural Science Foundation of Jiangsu Province (BK20211504)+4 种基金Social Development Project of Jiangsu Province (BE2021646)Jiangsu Province"333 Project"talent project (2069999)Suzhou Gusu Health Talent Program (GSWS2020001,GSWS2021009,GSWS2021007)Jiangsu Innovative and Enterpreneurial Talent Program (JSSCBS20211570)Medical Health Science and Technology Innovation Program of Suzhou (SKY2022119).
文摘Sustained and intense inflammation is the pathological basis for intervertebral disc degeneration(IVDD).Effective antagonism or reduction of local inflammatory factors may help regulate the IVDD microenvironment and reshape the extracellular matrix of the disc.This study reports an immunomodulatory hydrogel microsphere system combining cell membrane-coated mimic technology and surface chemical modification methods by grafting neutrophil membrane-coated polylactic-glycolic acid copolymer nanoparticles loaded with transforming growth factor-beta 1(TGF-β1)(T-NNPs)onto the surface of methacrylic acid gelatin anhydride microspheres(GM)via amide bonds.The nanoparticle-microsphere complex(GM@T-NNPs)sustained the long-term release of T-NNPs with excellent cell-like functions,effectively bound to pro-inflammatory cytokines,and improved the release kinetics of TGF-β1,maintaining a 36 day-acting release.GM@T-NNPs significantly inhibited lipopolysaccharide-induced inflammation in nucleus pulposus cells in vitro,downregulated the expression of inflammatory factors and matrix metalloproteinase,and upregulated the expression of collagen-II and aggrecan.GM@T-NNPs effectively restored intervertebral disc height and significantly improved the structure and biomechanical function of the nucleus pulposus in a rat IVDD model.The integration of biomimetic technology and nano-drug delivery systems expands the application of biomimetic cell membrane-coated materials and provides a new treatment strategy for IVDD.
基金supported by the Defense Threat Reduction Agency Joint Science and Technology Office for Chemical and Biological Defense under award number HDTRA1-21-1-0010the National Institutes of Health under Award Numbers R21AI159492 and R21AI175904.
文摘Given their dangerous effects on the nervous system,neurotoxins represent a significant threat to public health.Various therapeutic approaches,including chelating agents,receptor decoys,and toxin-neutralizing antibodies,have been explored.While prophylactic vaccines are desirable,it is oftentimes difficult to effectively balance their safety and efficacy given the highly dangerous nature of neurotoxins.To address this,we report here on a nanovaccine against neurotoxins that leverages the detoxifying properties of cell membrane-coated nanoparticles.A genetically modified cell line with constitutive overexpression of theα7 nicotinic acetylcholine receptor is developed as a membrane source to generate biomimetic nanoparticles that can effectively and irreversibly bind toα-bungarotoxin,a model neurotoxin.This abrogates the biological activity of the toxin,enabling the resulting nanotoxoid to be safely delivered into the body and processed by the immune system.When co-administered with an immunological adjuvant,a strong humoral response againstα-bungarotoxin is generated that protects vaccinated mice against a lethal dose of the toxin.Overall,this work highlights the potential of using genetic modification strategies to develop nanotoxoid formulations against various biological threats.
基金supported by the National Natural Science Foundation of China(NSFC 32071323 and 32271410)Program for Innovative Research Team in Science and Technology in Fujian Province University,Scientific Research Funds of Huaqiao University(22BS125).
文摘Atherosclerosis(AS)has emerged as one of the prevalent arterial vascular diseases characterized by plaque and inflammation,primarily causing disability and mortality globally.Drug therapy remains the main treatment for AS.However,a series of obstacles hinder effective drug delivery.Nature,from natural micro-/nano-structural biological particles like natural cells and extracellular vesicles to the distinctions between the normal and pathological microenvironment,offers compelling solutions for efficient drug delivery.Nature-inspired nanocarriers of synthetic stimulus-responsive materials and natural components,such as lipids,proteins and membrane structures,have emerged as promising candidates for fulfilling drug delivery needs.These nanocarriers offer several advantages,including prolonged blood circulation,targeted plaque delivery,targeted specific cells delivery and controlled drug release at the action site.In this review,we discuss the nature-inspired nanocarriers which leverage the natural properties of cells or the microenvironment to improve atherosclerotic drug therapy.Finally,we provide an overview of the challenges and opportunities of applying these innovative nature-inspired nanocarriers.
基金supported by the National Natural Science Foundation of China (Grant Nos.81773648 and 81973267,China)。
文摘Cancer immunotherapy can effectively inhibit cancer progression by activating the autoimmune system, with low toxicity and high effectiveness. Some of cancer immunotherapy had positive effects on clinical cancer treatment. However, cancer immunotherapy is still restricted by cancer heterogeneity, immune cell disability, tumor immunosuppressive microenvironment and systemic immune toxicity. Cell membrane-coated nanoparticles(CMCNs) inherit abundant source cell-relevant functions, including “self” markers, cross-talking with the immune system, biological targeting, and homing to specific regions. These enable them to possess preferred characteristics, including better biological compatibility, weak immunogenicity, immune escaping, a prolonged circulation, and tumor targeting.Therefore, they are applied to precisely deliver drugs and promote the effect of cancer immunotherapy.In the review, we summarize the latest researches of biomimetic CMCNs for cancer immunotherapy,outline the existing specific cancer immune therapies, explore the unique functions and molecular mechanisms of various cell membrane-coated nanoparticles, and analyze the challenges which CMCNs face in clinical translation.
