Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective deli...Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells.To be excited,the development of ionizable drug delivery systems(IDDSs)has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019(COVID-19)in 2021.Compared with conventional cationic gene vectors,IDDSs can decrease the toxicity of carriers to cell membranes,and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures.Despite the progress,there remain necessary requirements for designing more efficient IDDSs for precise gene therapy.Herein,we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms.The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of plasmid DNA(pDNA)and four kinds of RNA.In particular,organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity.We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future,and indicate ideas for developing next generation gene vectors.展开更多
Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)re...Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)remains a challenge mainly due to the obstruction from brain barriers.Immune cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug delivery.Herein,we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood–brain barrier.We subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS,as well as recent progress in rationally engineering immune cell-based DDS for CNS diseases.Finally,we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.展开更多
Titanium dioxide(TiO2)nanostructures exhibit a broad range of theranostic properties that make them attractive for biomedical applications.TiO2 nanostructures promise to improve current theranostic strategies by lever...Titanium dioxide(TiO2)nanostructures exhibit a broad range of theranostic properties that make them attractive for biomedical applications.TiO2 nanostructures promise to improve current theranostic strategies by leveraging the enhanced quantum confinement,thermal conversion,specific surface area,and surface activity.This review highlights certain important aspects of fabrication strategies,which are employed to generate multifunctional TiO2 nanostructures,while outlining post-fabrication techniques with an emphasis on their suitability for nanomedicine.The biodistribution,toxicity,biocompatibility,cellular adhesion,and endocytosis of these nanostructures,when exposed to biological microenvironments,are examined in regard to their geometry,size,and surface chemistry.The final section focuses on recent biomedical applications of TiO2 nanostructures,specifically evaluating therapeutic delivery,photodynamic and sonodynamic therapy,bioimaging,biosensing,tissue regeneration,as well as chronic wound healing.展开更多
In this formulation study,biocompatible non steroidal anti-inflammatory(NSAIDs)-loaded nanoparticles were designed as models to be further integrated in a prosthesis surface functionalization.A modified spontaneous em...In this formulation study,biocompatible non steroidal anti-inflammatory(NSAIDs)-loaded nanoparticles were designed as models to be further integrated in a prosthesis surface functionalization.A modified spontaneous emulsion-solvent diffusion methodology was used to produce drug-loaded PLGA nanoparticles without any purification or solvent evaporation requirements.Formulation parameters,such as lactide/glycolide ratio,polymer concentration,solvent/non solvent ratio and non solvent phase,as well as the non ionic tensioactive P188 co-precipitation composition were systematically explored.The optimized formulation(mean size:145 nm,surface charge:-13 m V) was employed to encapsulate various amounts of NSAIDs in a simple and scalable manner.The drug release was characterized in vitro by a complete release for 48 h.These results encourage upcoming preliminary steps for in vivo experiments of prosthesis surface functionalization.展开更多
文摘Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells.To be excited,the development of ionizable drug delivery systems(IDDSs)has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019(COVID-19)in 2021.Compared with conventional cationic gene vectors,IDDSs can decrease the toxicity of carriers to cell membranes,and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures.Despite the progress,there remain necessary requirements for designing more efficient IDDSs for precise gene therapy.Herein,we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms.The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of plasmid DNA(pDNA)and four kinds of RNA.In particular,organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity.We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future,and indicate ideas for developing next generation gene vectors.
基金supported by the National Natural Science Foundation of China(82204634,82174047,81622051)the Zhejiang Provincial Natural Science Foundation of China(LQ22H280010)the Foundation of Zhejiang Chinese Medical University(2021ZR03).
文摘Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)remains a challenge mainly due to the obstruction from brain barriers.Immune cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug delivery.Herein,we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood–brain barrier.We subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS,as well as recent progress in rationally engineering immune cell-based DDS for CNS diseases.Finally,we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.
基金supported by the Alexander von Humboldt Foundation(MHK)European Union Horizon 2020 program Phys2Bio Med,EU H2020-MSCA-ITN-2018(WHG)
文摘Titanium dioxide(TiO2)nanostructures exhibit a broad range of theranostic properties that make them attractive for biomedical applications.TiO2 nanostructures promise to improve current theranostic strategies by leveraging the enhanced quantum confinement,thermal conversion,specific surface area,and surface activity.This review highlights certain important aspects of fabrication strategies,which are employed to generate multifunctional TiO2 nanostructures,while outlining post-fabrication techniques with an emphasis on their suitability for nanomedicine.The biodistribution,toxicity,biocompatibility,cellular adhesion,and endocytosis of these nanostructures,when exposed to biological microenvironments,are examined in regard to their geometry,size,and surface chemistry.The final section focuses on recent biomedical applications of TiO2 nanostructures,specifically evaluating therapeutic delivery,photodynamic and sonodynamic therapy,bioimaging,biosensing,tissue regeneration,as well as chronic wound healing.
基金financially supported by the European Erasmus program
文摘In this formulation study,biocompatible non steroidal anti-inflammatory(NSAIDs)-loaded nanoparticles were designed as models to be further integrated in a prosthesis surface functionalization.A modified spontaneous emulsion-solvent diffusion methodology was used to produce drug-loaded PLGA nanoparticles without any purification or solvent evaporation requirements.Formulation parameters,such as lactide/glycolide ratio,polymer concentration,solvent/non solvent ratio and non solvent phase,as well as the non ionic tensioactive P188 co-precipitation composition were systematically explored.The optimized formulation(mean size:145 nm,surface charge:-13 m V) was employed to encapsulate various amounts of NSAIDs in a simple and scalable manner.The drug release was characterized in vitro by a complete release for 48 h.These results encourage upcoming preliminary steps for in vivo experiments of prosthesis surface functionalization.
