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

• 成果类型: Article
• 署名作者: Ma, Xiqi; Zhang, Zhixiong; Barba-Bon, Andrea; Han, Dongxue; Qi, Zichun; Ge, Baosheng; He, Hua; Huang, Fang; Nau, Werner M.; Wang, Xiaojuan
• 署名单位: China University of Petroleum; Constructor University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13654
• DOI: 10.1073/pnas.2407515121
• 发表日期: 2024-10-29
• 关键词: cell-penetrating peptides; mesoporous silica nanoparticles; cytochrome-c; dodecaborate clusters; refractive-index; boron clusters; fluorescence; transport; binding; tumors

摘要

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 mu M). 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.