A small-molecule carrier for the intracellular delivery of a membrane-impermeable protein with retained bioactivity.

Autor: Xiqi Ma, Zhixiong Zhang, Barba-Bon, Andrea, Dongxue Han, Zichun Qi, Baosheng Ge, Hua He, Fang Huang, Nau, Werner M., Xiaojuan Wang
Předmět:
Zdroj: Proceedings of the National Academy of Sciences of the United States of America; 10/29/2024, Vol. 121 Issue 44, p1-10, 20p
Abstrakt: Intracellular protein delivery has the potential to revolutionize cell-biological research and medicinal therapy, with broad applications in bioimaging, disease treatment, and genome editing. Herein, we demonstrate successful delivery of a functional protein, cytochrome c (CYC), by using a boron cluster anion as molecular carrier of the superchaotropic anion type (B12Br11OPr2-). CYC was delivered into lipid bilayer vesicles as well as living cells, with a cellular uptake ratio approaching 90%. Mechanistic studies showed that CYC was internalized into cells through a permeation pathway directly into the cytoplasm, bypassing endosomal entrapment. Upon carrier-assisted internalization, CYC retained its bioactivity, as reflected by an induced cell apoptosis rate of 25% at low dose (1 µM). This study furbishes a direct protein delivery method by a molecular carrier with high efficiency, confirming the potential of inorganic cluster ions as protein transport vehicles with an extensive range of future cell-biological or biomedical applications. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index