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

Abstract Chemodynamic therapy (CDT) involves the catalytic generation of highly toxic hydroxyl radicals ( . OH) from hydrogen peroxide (H 2 O 2 ) through metal‐ion‐mediated Fenton or Fenton‐like reactions. Fe 2+ is a classical catalyst ion, however, it suffers easy oxidation and systemic side‐effects. Therefore, the development of a controllable Fe 2+ 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 2+ 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 2+ from its hydrophobic layer, which primes the catalytic breakdown of endogenous H 2 O 2 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 2+ delivery system provides a sound basis for future synergistic metal‐ion‐mediated cancer therapy.