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 H 2 O 2 ‐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 Fe 2+ 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 Fe 3+ and tannic acid (Fe‐TA) onto the surfaces of Er 3+ , Ce 3+ , and Tm 3+ co‐doped core‐shell nanoparticles. At an optimal Tm 3+ 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 Fe 3+ ‐to‐Fe 2+ 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 3d 5 electronic reorganization of Fe 3+ 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.