Ni-engineered FeS₂ nanostructures (Ni_xFe_1-xS₂) for enhanced photothermal and photodynamic cancer therapy: Mechanistic insights and bioactivity evaluation

The development of precise, multimodal anticancer nanotherapeutics remains an urgent clinical need due to limitations in tumor selectivity and therapeutic efficacy. Herein, we engineered a series of Ni-doped FeS₂ nanostructures (Ni_xFe_1-xS₂) to achieve a reactive oxygen species (ROS)-mediated photothermal-photodynamic therapy (PTT-PDT) platform targeting MCF-7 breast cancer cells. Among them, NFS-0.4 exhibited optimized bandgap (1.56 eV), highest photoluminescence (PL) quenching, elevated ROS generation (215 a.u), and superior photothermal efficiency (ΔT_max 20.4 °C on 660 nm irradiation). The therapeutic regimen triggered apoptosis through Bax/Bcl-2 modulation, p53 upregulation, and caspase activation, leading to >98% in-vitro cell death. In-vivo tumor inhibition was confirmed by significant tumor volume reduction (∼5.4 fold) without affecting body weight or organ function. Mechanistically, the treatment activated intrinsic mitochondrial pathways and oxidative stress cascades, validating its multipronged impact. This study demonstrates clinically translatable nanomaterials for efficient, minimally invasive cancer treatment.