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

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, F(6)G(6)(rR)(3)R-2, 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 F(6)G(6)(rR)(3)R-2 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.