A Near-Infrared-II\nFluorescent Nanoprobe Offering\nReal-Time Tracking of Fenton-Like Reaction for Cancer Chemodynamic\nTheranostics

Chemodynamic\ntherapy (CDT) utilizing Fenton or Fenton-like reactions\nto generate cytotoxic hydroxyl radicals by metal ions has become a\ncompelling strategy for cancer treatment. Visualizing intratumoral\nFenton or Fenton-like reactions especially at a cellular level in\nreal-time can directly monitor the process of CDT, which is not yet\nfeasible. Here, we present a molecule BADA chelating Cu<sup>2+</sup> to form Cu-BADA nanoparticles, exhibiting fluorescence quenching\nproperties through intermolecular electron transfer. The nanoparticles\nare lit up owing to glutathione and acid dual activatable Fenton-like\nreaction and generation of near-infrared-II fluorescent <i>o</i>-quinones. Moreover, fluorescence vanishing correlated with the decreased\nintratumoral Cu concentration, thus enabling to track the “on–off”\nprocess of Fenton-like reaction specifically in the tumor. Compared\nto 660 nm-excitation, the <i>o</i>-quinones excited at 830\nnm offer deeper tissue near-infrared-II fluorescence imaging with\nhigher resolution. Our results demonstrate a fluorescence nanotheranostic\nagent for CDT capable of monitoring the spatiotemporal dynamics of\nFenton-like reaction.