Light-Triggered Transformable Ferrous Ion Delivery System for Photothermal Primed Chemodynamic Therapy.

Chemodynamic therapy (CDT) involves the catalytic generation of highly toxic hydroxyl radicals ( OH) from hydrogen peroxide (H O ) through metal-ion-mediated Fenton or Fenton-like reactions. Fe is a classical catalyst ion, however, it suffers easy oxidation and systemic side-effects. Therefore, the development of a controllable Fe delivery system is a challenge to maintain its valence state, reduce toxicity, and improve therapeutic efficacy. Reported here is a near-infrared (NIR) light-triggered Fe delivery agent (LET-6) for fluorescence (FL) and photoacoustic (PA) dual-modality imaging guided, photothermal primed CDT. Thermal expansion caused by 808 nm laser irradiation triggers the transformation of LET-6 to expose Fe from its hydrophobic layer, which primes the catalytic breakdown of endogenous H O within the tumor microenvironment, thus generating OH for enhanced CDT. LET-6 shows remarkable therapeutic effects, both in vitro and in vivo, achieving 100 % tumor elimination after just one treatment. This high-performance Fe delivery system provides a sound basis for future synergistic metal-ion-mediated cancer therapy.