Cell-Penetrating Peptides Transport Noncovalently Linked Thermally Activated Delayed Fluorescence Nanoparticles for Time-Resolved Luminescence Imaging

• Published in: Journal of the American Chemical Society Vol. 140; no. 50; pp. 17484 - 17491
• Main Authors: Zhu, Zece, Tian, Di, Gao, Pengli, Wang, Ke, Li, Yuce, Shu, Xuewen, Zhu, Jintao, Zhao, Qiang
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 19.12.2018
• Subjects: aqueous solutions; cell membranes; cytotoxicity; fluorescence; fluorescent dyes; hydrophobicity; image analysis; nanoparticles; peptides; permeability
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/jacs.8b08438

Luminescent probes and nanoparticles (NPs) with long excited state lifetimes are essential for time-resolved biological imaging. Generally, cell membranes are physiological barriers that could prevent the uptake of many unnatural compounds. It is still a big challenge to prepare biocompatible imaging agents with high cytomembrane permeability, especially for nonmetallic NPs with long-lived luminescence. Herein, an amphiphilic cell-penetrating peptide, F6G6(rR)3R2, was designed to transport hydrophobic fluorophores across cellular barriers. Three classical thermally activated delayed fluorescence (TADF) molecules, 4CzIPN, NAI-DPAC, and BTZ-DMAC, could self-assemble into well-dispersed NPs with F6G6(rR)3R2 in aqueous solution. These NPs showed low cytotoxicity and could penetrate membranes easily. Moreover, long-lived TADF enabled them to be used in time-resolved luminescence imaging in oxygenic environments. These findings greatly expanded the applications of cell-penetrating peptides for delivery of molecules and NPs by only noncovalent interactions, which were more flexible and easier than covalent modifications.