Supramolecular Self-Assemblies with Spatiotemporal Controllable NO Release and Bioimaging Behavior toward RNS-Augmented Chemodynamic Therapy

Reactive nitrogen species (RNS)-based therapy is promising for cancer treatment, but codelivery of nitric oxide (NO) and superoxide anions (•O2–) is hindered by their short lifetimes and uncontrolled release. In this paper, we present a light-activated supramolecular theranostic system integrating NO release with chemodynamic therapy (CDT). β-Cyclodextrin-grafted hyaluronic acid (HA-CD) and a photoresponsive NO donor (Fc-NAp-NO) self-assemble into nanocarriers, further loaded with ascorbyl palmitate (PA) to supply H2O2. Upon irradiation, precise NO release and fluorescence imaging occur, while CDT yields •OH and •O2–. The •O2– rapidly reacts with NO to generate cytotoxic peroxynitrite (ONOO–), amplifying RNS/ROS damage. This platform prevents achieved spatiotemporal control NO release, imaging-guided and cascade-enhanced tumor therapy.