Novel Near-Infrared Fluorescent Nanoprobe Synthesized by the RAFT-Mediated PISA Strategy for Hypoxia-Triggered Tumor Imaging and Azoreductase-Responsive Drug Release

Drug carriers and visual tracking play an important role in accurate and efficient drug delivery systems for targeted drug therapy. Polymerization-induced self-assembly (PISA), a powerful strategy for the fabrication of stimuli-responsive polymeric nanoparticles has been a focus over the past decade due to its promising applications in biomedical fields such as targeted drug delivery and fluorescent nanoprobes used for tumor imaging. Herein, hypoxia-responsive near-infrared (NIR) fluorescent nanoprobes of amphiphilic block copolymers (PPEGMA(14)-ADP-Azo-PBzMA(x)) are reported, the first example synthesized by RAFT-mediated PISA strategy in situ to realize synchronous drug release and cell imaging. First, a series of nanoparticles with different morphologies and sizes, including spheres and vesicles, are synthesized by the PISA strategy using PPEGMA(14)-ADP-Azo-CDPA as macro-RAFT agents link with near-infrared Aza-BODIPY fluorogen and azobenzene groups. Hypoxia-triggered dissociation of the nanoprobes and NIR fluorescence emission is then observed because of the cleavage of azo bonds. Meanwhile, the in situ DOX-loaded nanoprobes by the PISA demonstrate synchronous drug release and NIR fluorescence enhancement against mouse colon cancer cells (CT26) under hypoxia (1% O-2) compared with under normoxia (16% O-2).

Automated summary

This study reports the synthesis of hypoxia-responsive near-infrared fluorescent nanoprobes through a RAFT-mediated PISA strategy, which enables synchronous drug release and cell imaging. The nanoparticles with different morphologies and sizes are synthesized by the PISA strategy, and the dissociation of the nanoprobes and NIR fluorescence emission are observed under hypoxia due to the cleavage of azo bonds. The in situ DOX-loaded nanoprobes by the PISA demonstrate synchronous drug release and NIR fluorescence enhancement against mouse colon cancer cells under hypoxia.