This study aims to develop a polydopamine-based nanoplatform loaded with Mn²⁺ (Mn-PDA, MD) and explore its mechanism and efficacy in hepatocellular carcinoma treatment through the combination of photothermal therapy and chemodynamic therapy.

MD was synthesized by self-oxidative polymerization and characterized by transmission electron microscopy, dynamic light scattering, and X-ray photoelectron spectroscopy for its structure and properties. Its photothermal performance, Mn²⁺ release characteristics in response to stimuli, and Fenton-like reaction catalytic activity were further evaluated. In vitro experiments were conducted to assess the survival rate of tumor cells using CCK-8 and live/dead staining, and to detect the effects of photothermal effect and Mn²⁺ release on cytotoxicity.

The synthesized MD had a particle size of approximately 200 nm. After 7 minutes of near-infrared (NIR) laser irradiation (1 W/cm²), the temperature rapidly rose to 47.2℃. NIR irradiation triggered the release of Mn²⁺ from MD, which further catalyzed the generation of hydroxyl radicals. In vitro experiments showed that at a concentration of 100 μg/ml and under NIR irradiation (1 W/cm², 10 min), MD reduced the viability of tumor cells to 40%. Live/dead staining further confirmed that a large number of tumor cells died. Compared with polydopamine, MD exhibited more significant killing ability, and the difference was statistically significant.

The developed MD achieved efficient killing of tumor cells through the combination of photothermal effect and Mn²⁺-mediated reactive oxygen species generation, demonstrating the advantages of synergistic therapy and providing a new strategy and direction for liver cancer treatment.