Nanoparticles of polystyrene/α Fe 2O 3 composites were prepared by method of insertion in sodium dodecylbenzene sulfonate(SDBS) micellar system. The orange α Fe 2O 3 particles of about 6 nm were first prepared from ...Nanoparticles of polystyrene/α Fe 2O 3 composites were prepared by method of insertion in sodium dodecylbenzene sulfonate(SDBS) micellar system. The orange α Fe 2O 3 particles of about 6 nm were first prepared from 0 25 mol/L FeCl 2 and (NH 3) 2CO 3 in 0.1% surfactant solution at pH=4, 105 ℃ for 10 h. The title nanoparticles were prepared then in conditions of SDBS∶ styrene∶H 2O(mass fraction)=0 1∶1∶9, 85 ℃, 8 h, using ammonium persulfate(APS) as an initiator. The composite nanoparticles sized in 20～50 nm and showed magnetic property.展开更多
Tumor vaccine is a promising strategy for cancer immunotherapy by introducing tumor antigens into the body to activate specific anti-tumor immune responses.Along with the technological breakthroughs in genetic enginee...Tumor vaccine is a promising strategy for cancer immunotherapy by introducing tumor antigens into the body to activate specific anti-tumor immune responses.Along with the technological breakthroughs in genetic engineering and delivery systems,messenger ribonucleic acid(mRNA)technology has achieved unprecedented development and application over the last few years,especially the emergency use authorizations of two mRNA vaccines during the COVID-19 pandemic,which has saved countless lives and makes the world witness the powerful efficacy of mRNA technology in vaccines.However,unlike infectious disease vaccines,which mainly induce humoral immunity,tumor vaccines also need to activate potent cellular immunity to control tumor growth,which creates a higher demand for mRNA delivery to the lymphatic organs and antigen-presenting cells(APCs).Here we review the existing bottlenecks of mRNA tumor vaccines and advanced nano-based strategies to overcome those challenges,as well as future considerations of mRNA tumor vaccines and their delivery systems.展开更多
To the Editor:Malignant brain tumors represent a substantial morbidity and mortality burden globally,with 308,102 new cases and 251,329 cancer-related deaths in 20201.Brain tumors encompass primary tumors originating ...To the Editor:Malignant brain tumors represent a substantial morbidity and mortality burden globally,with 308,102 new cases and 251,329 cancer-related deaths in 20201.Brain tumors encompass primary tumors originating in the brain and brain metastases(BM)that have been spread from cancer lesions of other organs.Besides,BM are the most prevalent intracranial malignant tumor affecting approximately 20%-40%of cancer patients2.展开更多
Objective:To prepare and characterize polycaprolactone(PCL)nanoparticles loaded with sonicator fragmented(SLA)and freeze-thaw Leishmania antigens(FTLA)and to investigate the in vitro immunogenicity of antigen-encapsul...Objective:To prepare and characterize polycaprolactone(PCL)nanoparticles loaded with sonicator fragmented(SLA)and freeze-thaw Leishmania antigens(FTLA)and to investigate the in vitro immunogenicity of antigen-encapsulated nanoparticles with calcium phosphate adjuvant.Methods:The water/oil/water binary emulsion solvent evaporation method was used to synthesize antigen-loaded PCL nanoparticles.Particles were characterized by scanning electron microscopy and zeta potential measurements.Their cytotoxicity in J774 macrophages in vitro was determined by MTT analysis.In addition,the amount of nitric oxide and the level of cytokines produced by macrophages were determined by Griess reaction and ELISA method,respectively.The protective effect of the developed formulations was evaluated by determining the infection index percentage in macrophages infected with Leishmania infantum.Results:Compared to the control group,SLA PCL and FTLA PCL nanoparticles with calcium phosphate adjuvant induced a 6-and 7-fold increase in nitric oxide,respectively.Additionally,the vaccine formulations promoted the production of IFN-γand IL-12.SLA PCL and FTLA PCL nanoparticles combined with calcium phosphate adjuvant caused an approximately 13-and 11-fold reduction in infection index,respectively,compared to the control group.Conclusions:The encapsulation of antigens obtained by both sonication and freeze-thawing into PCL nanoparticles and the formulations with calcium phosphate adjuvant show strong in vitro immune stimulating properties.Therefore,PCL-based antigen delivery systems and calcium phosphate adjuvant are recommended as a potential vaccine candidate against leishmaniasis.展开更多
Lipid nanoparticles(LNPs)have delivered RNA to hepatocytes in patients after intravenous administration.These clinical data support efforts to design LNPs that transfect cells in the central nervous system(CNS).Howeve...Lipid nanoparticles(LNPs)have delivered RNA to hepatocytes in patients after intravenous administration.These clinical data support efforts to design LNPs that transfect cells in the central nervous system(CNS).However,delivery to the CNS has been difficult,in large part because quantifying on-target delivery alongside common off-target cell types in adult mice remains challenging.Here we report methods to isolate different cell types from the CNS,and subsequently present mRNA delivery readouts using a liver-detargeted LNP.These data suggest that LNPs without targeting ligands can transfect cerebral endothelial cells in mice after intravenous administration.Given the difficulty of crossing the blood-brain barrier,they also underscore the value of quantifying delivery in the CNS with cell-type resolution instead of whole-tissue resolution.展开更多
A light-switchable transgene system called LightOn gene expression system could regulate gene expression with a high on/off ratio under blue light,and have great potential for spatiotemporally controllable gene expres...A light-switchable transgene system called LightOn gene expression system could regulate gene expression with a high on/off ratio under blue light,and have great potential for spatiotemporally controllable gene expression.We developed a nanoparticle drug delivery system(NDDS)to achieve tumor microenvironment-responsive and targeted delivery of diphtheria toxin A(DTA)fragment-encoded plasmids to tumor sites.The expression of DTA was induced by exposure to blue light.Nanoparticles composed of polyethylenimine and vitamin E succinate linked by a disulfide bond,and PEGylated hyaluronic acid modified with RGD peptide,accumulated in tumor tissues and were actively internalized into 4 T1 cells via dual targeting to CD44 andαvβ3 receptors.The LightOn gene expression system was able to control target protein expression through regulation of the intensity or duration of blue light exposure.In vitro studies showed that lisht-induced DTA expression reduced 4 T1 cell viability and induced apoptosis.Furthermore,the LightOn gene expression system enabled spatiotemporal control of the expression of DTA in a mouse 4 T1 tumor xenogratt model,which resulted in excellent antitumor effects,reduced tumor angiogenesis,and no systemic toxicity.The combination of the LightOn gene expression system and NDDS may be an effective strategy for treatment of breast cancer.展开更多
RNA-based nanomedicines encompass a range of therapeutic approaches that utilize RNA molecules or molecules that target RNAs for the treatment or prevention of diseases.These include antisense oligonucleotides(ASOs),s...RNA-based nanomedicines encompass a range of therapeutic approaches that utilize RNA molecules or molecules that target RNAs for the treatment or prevention of diseases.These include antisense oligonucleotides(ASOs),small interfering RNAs(siRNAs),endogenous microRNAs(miRNAs),messenger RNAs(mRNAs),clustered regularly interspersed short palindromic repeats-associated protein 9(CRISPR/Cas9),single guide RNAs(sgRNAs),as well as RNA aptamers.These therapeutic agents exert their effects through various mechanisms such as gene inhibition,addition,replacement,and editing.The advancement of RNA biology and the field of RNA therapy has paved the way for the development and utilization of RNA-based nanomedicine in human healthcare.One remarkable example of RNA-based nanomedicine is the mRNA-based vaccines including mRNA-1273(Moderna)and BNT162b2(Pfizer/BioNTech)that have been successfully employed in response to the coronavirus disease 2019(COVID-19)pandemic.This review aims to highlight the advantages of RNA-based nanomedicines,provides an overview of significant developments in delivery systems,elucidates the molecular mechanisms of action underlying RNA-based nanomedicines,and discusses their clinical applications.Additionally,the review will address the existing challenges and innovations in delivery platforms while exploring the future possibilities for these promising RNA-based nanomedicines.展开更多
Chitosan is a natural polysaccharide prepared by the N-deacetylation of chitin. In this paper we have reviewed the methods of preparation of chitosan-based nanoparticles and their pharmaceutical applications. There ar...Chitosan is a natural polysaccharide prepared by the N-deacetylation of chitin. In this paper we have reviewed the methods of preparation of chitosan-based nanoparticles and their pharmaceutical applications. There are five methods of their prepa-rations:emulsion cross-linking,emulsion-droplet coalescence,ionic gelation,reverse micellar method and chemically modified chi-tosan method. Chitosan nanoparticles are used as carriers for low molecular weight drug,vaccines and DNA. Releasing characteris-tics,biodistribution and applications are also summarized.展开更多
For subunit vaccines,adjuvants play a key role in shaping the magnitude,persistence and form of targeted antigen-specific immune response.Flagellin is a potent immune activator by bridging innate inflammatory response...For subunit vaccines,adjuvants play a key role in shaping the magnitude,persistence and form of targeted antigen-specific immune response.Flagellin is a potent immune activator by bridging innate inflammatory responses and adaptive immunity and an adjuvant candidate for clinical application.Calcium phosphate nanoparticles are efficient carriers for different biomolecules like DNA,RNA,peptides and proteins.Flagellin-functionalized calcium phosphate nanoparticles were prepared and their immunostimulatory effect on the innate immune system,i.e.the cytokine production,was studied.They induced the production of the proinflammatory cytokines IL-8 （Caco-2 cells） and IL-1β（bone marrow-derived macrophages; BMDM） in vitro and IL-6 in vivo after intraperitoneal injection in mice.The immunostimulation was more pronounced than with free flagellin.展开更多
文摘Nanoparticles of polystyrene/α Fe 2O 3 composites were prepared by method of insertion in sodium dodecylbenzene sulfonate(SDBS) micellar system. The orange α Fe 2O 3 particles of about 6 nm were first prepared from 0 25 mol/L FeCl 2 and (NH 3) 2CO 3 in 0.1% surfactant solution at pH=4, 105 ℃ for 10 h. The title nanoparticles were prepared then in conditions of SDBS∶ styrene∶H 2O(mass fraction)=0 1∶1∶9, 85 ℃, 8 h, using ammonium persulfate(APS) as an initiator. The composite nanoparticles sized in 20～50 nm and showed magnetic property.
基金This work was supported by National Natural Science Funds of China(Nos.92059110 and 81872808)Development Fund for Shanghai Talents(No.2020090,China)+3 种基金Natural Science Foundation of Shanghai Science and Technology Innovation Plan(No.22ZR1414100,China)FDU 2025-Excellence Program Fund,Project Supported by Shanghai Municipal Science and Technology Major Project(No.2018SHZDZX01,China)ZJLab,Shanghai Post-doctoral Excellence Program(No.2033016,China)China Postdoctoral Science Foundation Funded Project(No.2023M730711).
文摘Tumor vaccine is a promising strategy for cancer immunotherapy by introducing tumor antigens into the body to activate specific anti-tumor immune responses.Along with the technological breakthroughs in genetic engineering and delivery systems,messenger ribonucleic acid(mRNA)technology has achieved unprecedented development and application over the last few years,especially the emergency use authorizations of two mRNA vaccines during the COVID-19 pandemic,which has saved countless lives and makes the world witness the powerful efficacy of mRNA technology in vaccines.However,unlike infectious disease vaccines,which mainly induce humoral immunity,tumor vaccines also need to activate potent cellular immunity to control tumor growth,which creates a higher demand for mRNA delivery to the lymphatic organs and antigen-presenting cells(APCs).Here we review the existing bottlenecks of mRNA tumor vaccines and advanced nano-based strategies to overcome those challenges,as well as future considerations of mRNA tumor vaccines and their delivery systems.
基金supported by the grant National Natural Science Foundation of China(82272951,82272953)Beijing Municipal Health Commission(Beijing Demonstration Research Ward BCRW20200303)Chinese Academy of Medical Sciences(2022-I2M-C&T-B-070).
文摘To the Editor:Malignant brain tumors represent a substantial morbidity and mortality burden globally,with 308,102 new cases and 251,329 cancer-related deaths in 20201.Brain tumors encompass primary tumors originating in the brain and brain metastases(BM)that have been spread from cancer lesions of other organs.Besides,BM are the most prevalent intracranial malignant tumor affecting approximately 20%-40%of cancer patients2.
文摘Objective:To prepare and characterize polycaprolactone(PCL)nanoparticles loaded with sonicator fragmented(SLA)and freeze-thaw Leishmania antigens(FTLA)and to investigate the in vitro immunogenicity of antigen-encapsulated nanoparticles with calcium phosphate adjuvant.Methods:The water/oil/water binary emulsion solvent evaporation method was used to synthesize antigen-loaded PCL nanoparticles.Particles were characterized by scanning electron microscopy and zeta potential measurements.Their cytotoxicity in J774 macrophages in vitro was determined by MTT analysis.In addition,the amount of nitric oxide and the level of cytokines produced by macrophages were determined by Griess reaction and ELISA method,respectively.The protective effect of the developed formulations was evaluated by determining the infection index percentage in macrophages infected with Leishmania infantum.Results:Compared to the control group,SLA PCL and FTLA PCL nanoparticles with calcium phosphate adjuvant induced a 6-and 7-fold increase in nitric oxide,respectively.Additionally,the vaccine formulations promoted the production of IFN-γand IL-12.SLA PCL and FTLA PCL nanoparticles combined with calcium phosphate adjuvant caused an approximately 13-and 11-fold reduction in infection index,respectively,compared to the control group.Conclusions:The encapsulation of antigens obtained by both sonication and freeze-thawing into PCL nanoparticles and the formulations with calcium phosphate adjuvant show strong in vitro immune stimulating properties.Therefore,PCL-based antigen delivery systems and calcium phosphate adjuvant are recommended as a potential vaccine candidate against leishmaniasis.
基金funded by the CMT Research Foundation(awarded to James E.Dahlman)supported by the Emory University Robert P.Apkarian Integrated Electron Microscopy Core Facility(RRID:SCR_023537)supported by the National Science Foundation Major Research Instrumentation(No.0923395).
文摘Lipid nanoparticles(LNPs)have delivered RNA to hepatocytes in patients after intravenous administration.These clinical data support efforts to design LNPs that transfect cells in the central nervous system(CNS).However,delivery to the CNS has been difficult,in large part because quantifying on-target delivery alongside common off-target cell types in adult mice remains challenging.Here we report methods to isolate different cell types from the CNS,and subsequently present mRNA delivery readouts using a liver-detargeted LNP.These data suggest that LNPs without targeting ligands can transfect cerebral endothelial cells in mice after intravenous administration.Given the difficulty of crossing the blood-brain barrier,they also underscore the value of quantifying delivery in the CNS with cell-type resolution instead of whole-tissue resolution.
基金supportedby Shanghai Municipal Natural Science Foundation(No.17ZR1406600,China)Science and Technology Commission of Shanghai Municipality(No.10DZ2220500,China)+1 种基金The Shanghai Committee of Science and Technology(Grant No.11DZ2260600,China)National Natural Science Foundation of China(Grant No.81973700)
文摘A light-switchable transgene system called LightOn gene expression system could regulate gene expression with a high on/off ratio under blue light,and have great potential for spatiotemporally controllable gene expression.We developed a nanoparticle drug delivery system(NDDS)to achieve tumor microenvironment-responsive and targeted delivery of diphtheria toxin A(DTA)fragment-encoded plasmids to tumor sites.The expression of DTA was induced by exposure to blue light.Nanoparticles composed of polyethylenimine and vitamin E succinate linked by a disulfide bond,and PEGylated hyaluronic acid modified with RGD peptide,accumulated in tumor tissues and were actively internalized into 4 T1 cells via dual targeting to CD44 andαvβ3 receptors.The LightOn gene expression system was able to control target protein expression through regulation of the intensity or duration of blue light exposure.In vitro studies showed that lisht-induced DTA expression reduced 4 T1 cell viability and induced apoptosis.Furthermore,the LightOn gene expression system enabled spatiotemporal control of the expression of DTA in a mouse 4 T1 tumor xenogratt model,which resulted in excellent antitumor effects,reduced tumor angiogenesis,and no systemic toxicity.The combination of the LightOn gene expression system and NDDS may be an effective strategy for treatment of breast cancer.
基金supported by the National Natural Science Foundation of China(No.32371458)the Key Research and Development Programs of the Ministry of Science and Technology(No.2022YFA1205700)+1 种基金the Basic Research Cooperation Special Foundation of Beijing-Tianjin-Hebei(Nos.H_(2)022205047,22JCZXJC00060,and E3B33911DF)funding from the National Center for Nanoscience and Technology and Chinese Academy of Sciences.
文摘RNA-based nanomedicines encompass a range of therapeutic approaches that utilize RNA molecules or molecules that target RNAs for the treatment or prevention of diseases.These include antisense oligonucleotides(ASOs),small interfering RNAs(siRNAs),endogenous microRNAs(miRNAs),messenger RNAs(mRNAs),clustered regularly interspersed short palindromic repeats-associated protein 9(CRISPR/Cas9),single guide RNAs(sgRNAs),as well as RNA aptamers.These therapeutic agents exert their effects through various mechanisms such as gene inhibition,addition,replacement,and editing.The advancement of RNA biology and the field of RNA therapy has paved the way for the development and utilization of RNA-based nanomedicine in human healthcare.One remarkable example of RNA-based nanomedicine is the mRNA-based vaccines including mRNA-1273(Moderna)and BNT162b2(Pfizer/BioNTech)that have been successfully employed in response to the coronavirus disease 2019(COVID-19)pandemic.This review aims to highlight the advantages of RNA-based nanomedicines,provides an overview of significant developments in delivery systems,elucidates the molecular mechanisms of action underlying RNA-based nanomedicines,and discusses their clinical applications.Additionally,the review will address the existing challenges and innovations in delivery platforms while exploring the future possibilities for these promising RNA-based nanomedicines.
文摘Chitosan is a natural polysaccharide prepared by the N-deacetylation of chitin. In this paper we have reviewed the methods of preparation of chitosan-based nanoparticles and their pharmaceutical applications. There are five methods of their prepa-rations:emulsion cross-linking,emulsion-droplet coalescence,ionic gelation,reverse micellar method and chemically modified chi-tosan method. Chitosan nanoparticles are used as carriers for low molecular weight drug,vaccines and DNA. Releasing characteris-tics,biodistribution and applications are also summarized.
基金supported by the Deutsche Forschungsgemeinschaft(SFB/Transregio 60)the National Natural Science Foundation of China(no.81302609 and 81202312)
文摘For subunit vaccines,adjuvants play a key role in shaping the magnitude,persistence and form of targeted antigen-specific immune response.Flagellin is a potent immune activator by bridging innate inflammatory responses and adaptive immunity and an adjuvant candidate for clinical application.Calcium phosphate nanoparticles are efficient carriers for different biomolecules like DNA,RNA,peptides and proteins.Flagellin-functionalized calcium phosphate nanoparticles were prepared and their immunostimulatory effect on the innate immune system,i.e.the cytokine production,was studied.They induced the production of the proinflammatory cytokines IL-8 （Caco-2 cells） and IL-1β（bone marrow-derived macrophages; BMDM） in vitro and IL-6 in vivo after intraperitoneal injection in mice.The immunostimulation was more pronounced than with free flagellin.
