Precise assembly of inside-out cell membrane camouflaged nanoparticles via bioorthogonal reactions for improving drug leads capturing  

作　　者：Xiaolin Zhang Xueyan Zhen Yixuan Yang Quan Feng Wanqing Yuan Xiaoyu Xie 

机构地区：[1]School of Pharmacy,Health Science Center,Xi'an Jiaotong University,Xi'an 710061,China [2]Shaanxi Engineering Research Center of Cardiovascular Drugs Screening&Analysis,Xi'an 710061,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第2期852-862,共11页药学学报（英文版）

基　　金：the National Natural Science Foundation of China(No.82073807)。

摘　　要：Cell membrane camouflaged nanoparticles have been widely used in the field of drug leads discovery attribute to their unique biointerface targeting function.However,random orientation of cell membrane coating does not guarantee effective and appropriate binding of drugs to specific sites,especially when applied to intracellular regions of transmembrane proteins.Bioorthogonal reactions have been rapidly developed as a specific and reliable method for cell membrane functionalization without disturbing living biosystem.Herein,inside-out cell membrane camouflaged magnetic nanoparticles(IOCMMNPs)were accurately constructed via bioorthogonal reactions to screen small molecule inhibitors targeting intracellular tyrosine kinase domain of vascular endothelial growth factor recptor-2.Azide functionalized cell membrane acted as a platform for specific covalently coupling with alkynyl functionalized magnetic Fe_(3)O_(4)nanoparticles to prepare IOCMMNPs.The inside-out orientation of cell membrane was successfully verified by immunogold staining and sialic acid quantification assay.Ultimately,two compounds,senkyunolide A and ligustilidel,were successfully captured,and their potential antiproliferative activities were further testified by pharmacological experiments.It is anticipated that the proposed inside-out cell membrane coating strategy endows tremendous versatility for engineering cell membrane camouflaged nanoparticles and promotes the development of drug leads discovery platforms.

关 键 词：Cell membrane camouflaged nanoparticles Inside-out cell membrane coating Bioorthogonal reactions Drug leads discovery Traditional Chinese medicine Magnetic nanoparticles Precise assembly Alkynyl functionalization 

分 类 号：R965.1[医药卫生—药理学]