A tumor microenvironment-responsive multifunctional MoS2-Ru nanocatalyst with photothermally enhanced chemodynamic activity

Targeting the unique characteristics of the tumor microenvironment (TME) has emerged as a highly promising strategy for cancer therapy. Chemodynamic therapy (CDT), which leverages the TME's intrinsic properties to convert H2O2 into cytotoxic hydroxyl radicals ((OH)-O-center dot), has attracted significant attention. However, the effectiveness of CDT is often limited by the catalytic efficiency of the materials used. Although Molybdenum disulfide (MoS2) exhibits remarkable chemodynamic and photothermal properties, its limited efficiency in catalyzing the conversion of endogenous H2O2 into (OH)-O-center dot radicals remains a significant challenge. To overcome this, we developed a nanocomposite of MoS2 and ruthenium (MoS2-Ru), by incorporating Ru into MoS2 nanosheets. The MoS2-Ru nanocomposite demonstrated significantly enhanced catalytic activity at a low concentration (500 ng mL-1), whereas the same effect was achieved only with 20 mu g mL-1 of MoS2. The low Michaelis-Menten constant (Km) of 4.69 mM further confirmed the superior catalytic activity of the nanocomposite, indicative of the enhanced enzyme-like activity. Additionally, the integration of Ru in MoS2 reduced the bandgap to 1.18 eV, facilitating near-infrared (NIR) absorption with a high conversion efficiency of 41%. Electron paramagnetic resonance (EPR) analysis confirmed robust (OH)-O-center dot radical generation driven by the combined chemodynamic and photothermal effects. In vitro studies using triple-negative breast cancer (TNBC) cells validated the synergistic activity of CDT and PTT, demonstrating significant (OH)-O-center dot radical production under TME conditions, leading to effective cancer cell death. This study underscores the potential of MoS2-Ru nanocomposites as a versatile and powerful platform for multimodal cancer therapy, seamlessly integrating CDT and PTT to achieve synergistic, precise, and highly effective treatment outcomes.