Natural Tannin and Upconversion Photons Co-Potentiate Fe Fenton Anticancer Therapy

Abstract

Chemodynamic therapy (CDT) is a tumor-specific catalytic therapeutic modality that harnesses metal ion-mediated Fenton/Fenton-like reactions within H₂O₂-overexpressed tumor tissues for anticancer purposes. However, their efficacy is limited by the low recycling rate of high- and low-valence metal ions. Herein, a Fe²⁺ self-supplied nano-platform (CSFT) is developed for near-infrared (NIR)-accelerated photo-Fenton CDT synergized with photothermal therapy, magnetic resonance imaging (MRI), and second near-infrared (NIR-II) imaging. Specifically, a CSFT nano-platform is synthesized by coating metal-coordinated polyphenol networks composed of Fe³⁺ and tannic acid (Fe-TA) onto the surfaces of Er³⁺, Ce³⁺, and Tm³⁺ co-doped core-shell nanoparticles. At an optimal Tm³⁺ doping content (1%), the upconversion (UC) ultraviolet signal of the core-shell nanoparticles is enhanced by 8.2-fold compared to that of the core, providing potential excitation energy for UC-driven photo-Fenton reactions and improving the Fe³⁺-to-Fe²⁺ conversion efficiency. Additionally, Fe-TA can absorb NIR photons and convert them into thermal energy, enhancing the photo-Fenton reaction and enabling photothermally enhanced CDT. The strong coordination effect of TA enables the 3d⁵ electronic reorganization of Fe³⁺ after their release from Fe-TA networks in acidic tumors, thus realizing tumor-specific self-enhanced MRI. This work demonstrates an NIR-promoted photo-Fenton platform through the engineering of metal-polyphenol networks on UC nanoparticles.