Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery,as demonstrated by the approval of patisiran for amyloidosis therapy in 2018.To illuminate the unique superiority of lipid nanovehicles...Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery,as demonstrated by the approval of patisiran for amyloidosis therapy in 2018.To illuminate the unique superiority of lipid nanovehicles in RNA delivery,in this review,we first introduce various RNA therapeutics,describe systemic delivery barriers,and explain the lipid components and methods used for lipid nanovehicle preparation.Then,we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA delivery.Finally,the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also discussed.Our objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery,inspiring the development of more high-performance RNA lipid nanovesicles in the future.展开更多
Lipid nanoparticles(LNPs)have emerged as a transformative platform for the delivery of nucleic acid therapeutics.1 A canonical LNP formulation typically comprises four key lipid components:an ionizable lipid,a helper ...Lipid nanoparticles(LNPs)have emerged as a transformative platform for the delivery of nucleic acid therapeutics.1 A canonical LNP formulation typically comprises four key lipid components:an ionizable lipid,a helper phospholipid,cholesterol,and a poly(ethylene glycol)(PEG)-lipid conjugate,often using PEG with a molecular weight of∼2000 Da.1 Within this system,PEG-lipids form a hydrated surface layer that prevents nanoparticle aggregation,facilitating improved manufacturability and colloidal stability.展开更多
Lipid nanoparticles(LNPs)have emerged as versatile and widely utilized delivery systems in both academic research and industrial applications,offering immense potential beyond liver-targeted and infectious disease tre...Lipid nanoparticles(LNPs)have emerged as versatile and widely utilized delivery systems in both academic research and industrial applications,offering immense potential beyond liver-targeted and infectious disease treatments.Despite their success,a significant limitation of LNPs is their inherent liver tropism following systemic administration.This liver-centric accumulation represents a key bottleneck,restricting the broader therapeutic applications of LNP-based delivery systems.In this review,we explore strategies to overcome this challenge by modulating LNP composition-including ionizable lipids,helper lipids,cholesterol,and other critical components-to achieve extrahepatic targeting.We further discuss recent advancements in surface modification techniques designed to redirect LNPs to organs beyond the liver.Additionally,we highlight recent progress in local delivery approaches,which offer a direct and effective alternative for achieving extrahepatic delivery.By providing a comprehensive overview of current strategies and limitations,we aim to guide future research efforts toward fully realizing the therapeutic potential of LNP-based delivery systems.展开更多
Oxidative deterioration of vegetable oils is of great importance in the food industry.In China,vegetable oils produced via thermal pretreatment are popular owing to their strong oil flavor and enhanced yield.Here,we r...Oxidative deterioration of vegetable oils is of great importance in the food industry.In China,vegetable oils produced via thermal pretreatment are popular owing to their strong oil flavor and enhanced yield.Here,we review:(i)the currently employed thermal treatment methods of oilseeds before oil extraction;(ii)effects of thermal treatments on the physicochemical properties,contents of minor lipid components,and oxidative stability of vegetable oils;and(iii)Maillard model systems that are related to oil and oilseed chemistry.Among the thermal pretreatment technologies,microwave and infrared radiations are promising,but these are not performed on the same large production scales as roasting.For most oilseeds,thermal treatments increase the yield of extracted oil and content of minor lipid compounds in the oil,such as polyphenols,tocopherols,and phytosterols.In addition,some Maillard reaction products(MRPs)generated by heating oilseeds have been extracted.The presence of both minor lipids and MRPs in the oil confers improved oxidative stability.However,the mechanism or relationship between thermal treatment and oxidative stability is yet to be clearly elucidated because vegetable oil oxidation is dependent on variables such as unsaturation,concentration and types of minor lipid components,MRPs,and the potential synergistic effects of these components.Recently,several Maillard reaction models related to thermally treated oilseeds have been established,suggesting that MRPs play a critical role during oxidation.However,comprehensive identification of antioxidants and the mechanism by which they inhibit oxidation are lacking.Future research can be performed to establish models that would help elucidate the antioxidative mechanisms of MRPs for more oilseeds.Using these models,it will be possible to predict the oil quality after processing,based on the presence of MRPs and oil chemistry.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82172098,81872428,81703010,and 82202344)the Shanghai Municipal Natural Science Foundation(23ZR1463300).
文摘Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery,as demonstrated by the approval of patisiran for amyloidosis therapy in 2018.To illuminate the unique superiority of lipid nanovehicles in RNA delivery,in this review,we first introduce various RNA therapeutics,describe systemic delivery barriers,and explain the lipid components and methods used for lipid nanovehicle preparation.Then,we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA delivery.Finally,the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also discussed.Our objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery,inspiring the development of more high-performance RNA lipid nanovesicles in the future.
基金supported by National Natural Science Foundation of China(NSFC)projects(52233009,52021002,and 52350348)YRD Collaborative Fundamental Research Project(2024CSJZN0800)+1 种基金Anhui Provincial Outstanding Youth Science Fund(2408085J035)Suzhou Cuttingedge Technologies Research Project(SYG202339).
文摘Lipid nanoparticles(LNPs)have emerged as a transformative platform for the delivery of nucleic acid therapeutics.1 A canonical LNP formulation typically comprises four key lipid components:an ionizable lipid,a helper phospholipid,cholesterol,and a poly(ethylene glycol)(PEG)-lipid conjugate,often using PEG with a molecular weight of∼2000 Da.1 Within this system,PEG-lipids form a hydrated surface layer that prevents nanoparticle aggregation,facilitating improved manufacturability and colloidal stability.
基金supported by the start-up package from the University of Massachusetts Lowell.
文摘Lipid nanoparticles(LNPs)have emerged as versatile and widely utilized delivery systems in both academic research and industrial applications,offering immense potential beyond liver-targeted and infectious disease treatments.Despite their success,a significant limitation of LNPs is their inherent liver tropism following systemic administration.This liver-centric accumulation represents a key bottleneck,restricting the broader therapeutic applications of LNP-based delivery systems.In this review,we explore strategies to overcome this challenge by modulating LNP composition-including ionizable lipids,helper lipids,cholesterol,and other critical components-to achieve extrahepatic targeting.We further discuss recent advancements in surface modification techniques designed to redirect LNPs to organs beyond the liver.Additionally,we highlight recent progress in local delivery approaches,which offer a direct and effective alternative for achieving extrahepatic delivery.By providing a comprehensive overview of current strategies and limitations,we aim to guide future research efforts toward fully realizing the therapeutic potential of LNP-based delivery systems.
基金supported by the National Natural Science Founda-tion of China(Grants No.31920103012 and 31901603)China Postdoc-toral Science Foundation(Grant No.2019M663386)the Science and Technology Project of Guangzhou City(Grant No.201903010049).
文摘Oxidative deterioration of vegetable oils is of great importance in the food industry.In China,vegetable oils produced via thermal pretreatment are popular owing to their strong oil flavor and enhanced yield.Here,we review:(i)the currently employed thermal treatment methods of oilseeds before oil extraction;(ii)effects of thermal treatments on the physicochemical properties,contents of minor lipid components,and oxidative stability of vegetable oils;and(iii)Maillard model systems that are related to oil and oilseed chemistry.Among the thermal pretreatment technologies,microwave and infrared radiations are promising,but these are not performed on the same large production scales as roasting.For most oilseeds,thermal treatments increase the yield of extracted oil and content of minor lipid compounds in the oil,such as polyphenols,tocopherols,and phytosterols.In addition,some Maillard reaction products(MRPs)generated by heating oilseeds have been extracted.The presence of both minor lipids and MRPs in the oil confers improved oxidative stability.However,the mechanism or relationship between thermal treatment and oxidative stability is yet to be clearly elucidated because vegetable oil oxidation is dependent on variables such as unsaturation,concentration and types of minor lipid components,MRPs,and the potential synergistic effects of these components.Recently,several Maillard reaction models related to thermally treated oilseeds have been established,suggesting that MRPs play a critical role during oxidation.However,comprehensive identification of antioxidants and the mechanism by which they inhibit oxidation are lacking.Future research can be performed to establish models that would help elucidate the antioxidative mechanisms of MRPs for more oilseeds.Using these models,it will be possible to predict the oil quality after processing,based on the presence of MRPs and oil chemistry.
