Engineered membrane-coated nanoparticles enhance ferroptosis and microtubule inhibition in prostate cancer.

Prostate cancer (PCa), characterized by its high incidence and progression to treatment-resistant stages, remains a major clinical challenge. Herein, we developed a membrane-coated Cabazitaxel (Cab)@TA-Fe³⁺ nanoplatform for enhanced PCa therapy. The nanoparticles demonstrated notable anticancer effects, with cytotoxicity increasing over time and with dose, along with significant inhibition of cell migration and induction of G2/M phase arrest in LNCaP cells. In addition, treatment markedly increased intracellular reactive oxygen species (ROS) levels, depleted glutathione (GSH), downregulated Glutathione Peroxidase 4 (GPX4) expression, and upregulated NADPH Oxidase 1 (NOX1) and Prostaglandin-Endoperoxide Synthase 2 (PTGS2), indicating enhanced ferroptosis. Ferrostatin-1 partially restored cell viability and reduced ROS accumulation, further supporting the involvement of ferroptosis. Mechanistically, the nanoplatform enables pH/GSH-responsive release of Cab and iron ions in the tumor microenvironment, promoting microtubule disruption and redox imbalance. These combined effects enhance tumor cell death. Overall, this study demonstrates that Cab@TA-Fe³⁺ nanoparticles significantly improve anticancer efficacy by integrating microtubule inhibition and ferroptosis induction, providing a promising strategy for prostate cancer treatment.