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

Abstract

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), 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 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 μg mL⁻¹ of MoS₂. The low Michaelis–Menten constant (K_m) 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 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 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.