Microenvironment-Driven Cascaded Responsive Hybrid Carbon Dots as a Multifunctional Theranostic Nanoplatform for Imaging-Traceable Gene Precise Delivery

Abstract

Imaging-guided stimuli-responsive delivery systems based on nanomaterials for cancer theranostics have been recognized as promising alternatives to traditional therapies in clinic. How to integrate multiple response-mediated nanoproperty (i.e., charge, size, or stability) transitions into a cascaded manner to overcome multistage biological barriers which usually demand different and even opposing nanoproperties in each stage is still a challenge. Herein, a multistage and cascaded responsive theranostic nanoplatform for imaging-traceable TRAIL gene precise delivery was prepared by a cleavable PEGylated shell and a fluorescent carbon dot (CD)-based core. The CDs as the core were prefunctionalized with polyethylenimine end-capped disulfide-bond-bearing hyperbranched poly(amido amine) (HPAP), endowing the CDs with enhanced fluorescent quantum yield (27%), intracellular degradability, and efficient gene delivery capability. The shell was fabricated by dimethylmaleic acid modification of mPEG-PEI600 copolymer a...