A Near-Infrared-II Fluorescent Nanoprobe Offering Real-Time Tracking of Fenton-Like Reaction for Cancer Chemodynamic Theranostics

Chemodynamic therapy (CDT) utilizing Fenton or Fenton-like reactions to generate cytotoxic hydroxyl radicals by metal ions has become a compelling strategy for cancer treatment. Visualizing intratumoral Fenton or Fenton-like reactions especially at a cellular level in real-time can directly monitor the process of CDT, which is not yet feasible. Here, we present a molecule BADA chelating Cu²⁺ to form Cu-BADA nanoparticles, exhibiting fluorescence quenching properties through intermolecular electron transfer. The nanoparticles are lit up owing to glutathione and acid dual activatable Fenton-like reaction and generation of near-infrared-II fluorescent o-quinones. Moreover, fluorescence vanishing correlated with the decreased intratumoral Cu concentration, thus enabling to track the "on-off" process of Fenton-like reaction specifically in the tumor. Compared to 660 nm-excitation, the o-quinones excited at 830 nm offer deeper tissue near-infrared-II fluorescence imaging with higher resolution. Our results demonstrate a fluorescence nanotheranostic agent for CDT capable of monitoring the spatiotemporal dynamics of Fenton-like reaction.