Ultra‐Sensitive Iron‐Doped Palladium Nanocrystals with Enhanced Hydroxyl Radical Generation for Chemo‐/Chemodynamic Nanotherapy

Abstract

Abstract Chemodynamic therapy (CDT) is a novel therapeutic modality that employs Fenton or Fenton‐like reaction to destroy cancer cells via the disproportionation of intratumoral hydrogen peroxide (H 2 O 2 ) to the highly toxic hydroxyl radical (·OH) without external energy input. A highly efficient chemodynamic catalyst in tumor microenvironment (TME) is key to effective anti‐tumor efficacy. Therefore, ultra‐sensitive FePd‐TPP/adriamycin (ADM) nanocrystals (NCs) are constructed via a simple thermal decomposition method with high catalytic efficiency for combined chemo‐/chemodynamic cancer nanotherapy. These FePd‐TPP/ADM NCs exhib high Fenton‐reaction efficiency with a Michaelis–Menten constant ( K m ) and maximum velocity ( V max ) of 3.65 m m and 1.69 × 10 −9 m s −1 , respectively. The ab‐initio molecular dynamics simulation based on density functional theory demonstrate that the repulsion effect between Pd and H atom contribute to the enhancement of the Fe 2+ mediated Fenton oxidation. Moreover, the doping of Fe enables FePd‐TPP/ADM NCs to be an efficient contrast agent for T 2 ‐weighted magnetic resonance imaging. Finally, upon intravenous injection, the FePd‐TPP/ADM NCs reveal synergistic tumor growth inhibition compared with chemotherapy and CDT alone. Considering the good biocompatibility and biosafety, this study may pave the way to design a theranostic nano‐platform based on palladium nanoparticles for various catalytic applications.