Precise assembly of inside-out cell membrane camouflaged nanoparticles via bioorthogonal reactions for improving drug leads capturing.
10.1016/j.apsb.2022.05.034
- Author:
Xiaolin ZHANG
1
;
Xueyan ZHEN
1
;
Yixuan YANG
1
;
Quan FENG
1
;
Wanqing YUAN
1
;
Xiaoyu XIE
1
Author Information
1. School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
- Publication Type:Journal Article
- Keywords:
Alkynyl functionalization;
Bioorthogonal reactions;
Cell membrane camouflaged nanoparticles;
Drug leads discovery;
Inside-out cell membrane coating;
Magnetic nanoparticles;
Precise assembly;
Traditional Chinese medicine
- From:
Acta Pharmaceutica Sinica B
2023;13(2):852-862
- CountryChina
- Language:English
-
Abstract:
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 Fe3O4 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.
