Amphiphilic Dendrimer Vectors for RNA Delivery:State-of-the-Art and Future  

作　　者：Jiaxuan Chen Dandan Zhu Xiaoxuan Liu Ling Peng 

机构地区：[1]Aix Marseille Université,CNRS,Center Interdisciplinaire de Nanoscience de Marseille,CINaM UMR 7325,“Equipe Labellisée Ligue Contre le Cancer”,13288 Marseille,France [2]State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases,Center of Drug Discovery,Center of Advanced Pharmaceuticals and Biomaterials,China Pharmaceutical University,210009 Nanjing,P.R.China

出　　处：《Accounts of Materials Research》2022年第5期484-497,共14页材料研究述评（英文）

基　　金：We are grateful for financial support from the Ligue Nationale Contre le Cancer(L.P.),Campus France PHC program CAI YUANPEI(L.P.,X.L);the French National Research Agency for funding of the Era-Net EURONANOMED European Research projects"Target4Cancer",“NANOGLIO",“INANO-GUN"(LP.);the European Union's Horizon 2020 research and innovation program H2020 NMBP“SAFE-N-MED-TECH”(No.814607,LP.,XL.);the China Schol arship Council(.C.),Campus France bourse Eiffel(.C.),CNRS;Aix-Marseille Universite.

摘　　要：Dendrimers,a special family of polymers,are particularly promising materials for various biomedical applications by virtue of their well-defined dendritic structure and cooperative multivalency.Specifically,in this Account,we present state-of-the-art amphiphilic dendrimers for nucleic acid delivery.Ribonucleic acid(RNA)molecules are fast becoming an important drug modality,particularly since the recent success of mRNA vaccines against COVID-19.Notably,RNA therapeutics offer the unique opportunity to treat diseases at the gene level and address“undruggable”targets.However,RNA therapeutics are not stable and have poor bioavailability,imposing the need for their protection and safe delivery by vectors to the sites-of-action to allow the desired therapeutic effects.Currently,the two most advanced nonviral vectors are based on lipids and polymers,with lipid vectors primarily exploiting the membrane-fusion mechanism and polymer vectors mainly endocytosis-mediated delivery.Notably,only lipid vectors have been advanced through to their clinical use in the delivery of,for example,the first siRNA drug and the first mRNA vaccine.The success of lipid vectors for RNA delivery has motivated research for further innovative materials as delivery vectors.Specifically,we have pioneered lipid/dendrimer conjugates,referred to as amphiphilic dendrimers,for siRNA delivery with the view to harnessing the delivery advantages of both lipid and polymer vectors while enjoying the unique structural features of dendrimers.These amphiphilic dendrimer vectors are lipid/dendrimer hybrids and are thus able to mimic lipid vectors and exploit membranefusion-mediated delivery,while simultaneously retaining the multivalent properties of polymer vectors that allow endocytosis-based delivery.In addition,they have precisely controllable and stable nanosized chemical structures and offer nanotechnology-based delivery.Effective amphiphilic dendrimer vectors share two important elements:chemical hydrophilic entities to bind RNA and RNA complex-stabili

关 键 词：BREAKTHROUGH retaining DESIRED 

分 类 号：O63[理学—高分子化学]