MoS2-Doped Iron Oxide Nanozyme with Co-Catalytic Enhancement for Tumor Ferroptosis Guided by Magnetic Resonance Imaging

Abstract

Fe₃O₄ nanoparticles exhibit therapeutic and diagnostic capabilities by inducing ferroptosis through reactive oxygen species generated by the Fenton reaction and enhancing magnetic resonance imaging (MRI) contrast. However, the efficacy of ferroptosis induced by Fe₃O₄ is limited by several factors, including low Fe²⁺ concentration, restricted Fenton-active sites, excessive glutathione (GSH), and insufficient acidity of tumor cells. In this study, MoS₂-doped Fe₃O₄, with peroxidase and glutathione oxidase-like activities, was functionalized with tamoxifen (TAM) and coated with bovine serum albumin (BSA) to construct Fe₃O₄/MoS₂@TAM/BSA (FMTB) nanoparticles. The incorporation of MoS₂ facilitated the generation of abundant oxygen vacancies, which increased the number of active sites, acted as a co-catalyst to accelerate the reduction of Fe³⁺ to Fe²⁺, and promoted GSH consumption, resulting in a 51.3% increase in Fenton activity and a 4.3-fold enhancement in GSH consumption compared to Fe₃O₄ alone. The released TAM inhibited mitochondrial complex I and improved tumor cellular acidity, thereby creating a conducive environment for the Fenton reaction. By enhancing peroxidase-like activity through co-catalysis and reducing cellular pH, FMTB achieved a 70.6% tumor growth inhibition, in contrast to the 20.8% inhibition observed with Fe₃O₄ alone. Furthermore, the FMTB-mediated tumor T₂-weighted MRI signal was attenuated by 17% compared to that of Fe₃O₄. Thus, this multienzyme-based platform presents a novel strategy for highly efficient ferroptosis therapy against tumors by enhancing Fenton reaction efficiency and depleting GSH.

Keywords: Fe3O4; Fenton reaction; Ferroptosis; Magnetic resonance imaging; Nanozyme.