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.