Concave-Octahedral Fe2+-Rich Fe-MOF/FU Nano-Blocks with Enhanced pH-Responsive Nanozyme Activity Toward Stimuli-Responsive Gels for Chemo-Chemodynamic Synergistic Therapy

Abstract

Hydroxyl radicals (·OH) offer exceptional potential for cancer treatment through reactive oxygen species (ROS) amplification and apoptotic induction. However, conventional Fe-based metal–organic framework (Fe-MOF) nanomaterials are limited by inadequate Fe2+ concentrations, resulting in suboptimal Fenton catalytic performance. This study presents concave octahedral Fe-MOF nanomaterials with integrated bimetallic Fe/Zn centers through controlled solvothermal synthesis. The nanoplatform exhibits high specific surface area (559 m2/g) and 5-fluorouracil (5-FU) loading efficiency (58.7%). These structural properties establish it as a potential nanobuilding block for constructing stimuli-responsive gels. With optimized Fe2+ content (57.3%), the Fe-MOF material shows enhanced nanozyme-like activity (Vmax = 4.58 × 10−7 M/s, Kcat = 1.83 × 10−3 s−1) for H2O2-mediated ·OH generation. The Fe-MOF@FU demonstrates pH-responsive drug release (76.5% at pH 5.0) and glutathione (GSH) depletion, synergistically enhancing oxidative stress. Biocompatibility studies confirm safety, while in vitro investigations show remarkable anticancer activity against 4T1 cells with 17.8% viability, supporting its dual role as an independent therapeutic agent and a functional component for future gel-based delivery systems.