MnFe ₂ O ₄ Nanospheres with NIR-II-Responsive Photothermal, Photodynamic, and Enzyme-Mimicking Chemodynamic Activities for Cancer Therapy

Near-infrared-II (NIR-II, 1000-1350 nm) phototherapy offers deep tissue penetration and precise tumor ablation, yet its efficacy is hindered by the heterogeneous tumor microenvironment (TME) (hypoxia, acidity, and elevated H₂O₂). Herein, MnFe₂O₄ nanospheres with TME-responsive and NIR-II-activatable properties were synthesized via a one-pot solvothermal method by varying the reaction time. Under 1064 nm irradiation, the optimized reaction time of 24 h nanoferrites (MFO-24) exhibited a photothermal conversion efficiency of 53.43% for PTT and generated singlet oxygen (¹O₂) with a quantum yield of 86.3% for PDT. In the TME, the MFO-24 catalyzed Fenton reactions (Fe²⁺/Fe³⁺, Mn²⁺/Mn⁴⁺) to produce hydroxyl radicals for chemodynamic therapy (CDT), while their catalase-like activity generated O₂ to relieve tumor hypoxia, thereby enhancing PDT efficacy. Notably, NIR-II-induced hyperthermia accelerated reactive oxygen species (ROS) generation, synergistically enhancing PDT and CDT. <i>In vitro</i> assays confirmed that the MFO-24 nanospheres exhibited good biocompatibility with normal cells while inducing significant cytotoxicity in tumor cells. This triple-modal nanosystem demonstrates a feasible strategy for engineering NIR-II/TME-responsive spinel ferrites for synergistic cancer therapy.