Erythrosine–Iron Oxide Nanoemulsions Combining Photodynamic Therapy with Ferroptosis-Mediated Cytotoxicity in Prostate Cancer

Abstract

Prostate cancer remains one of the leading causes of cancer-related death among men worldwide. Photodynamic therapy (PDT) has emerged as a promising strategy to enhance conventional treatments, yet its efficacy is often limited by poor solubility, instability, and a lack of targeting of photosensitizers. Here, we report the development of hybrid erythrosine–iron oxide nanoemulsions (MNE/Ery) produced by vacuum-assisted nanoemulsification. The optimized formulation (0.05 mg·mL–1 erythrosine; 0.5 mg·mL–1 maghemite) exhibited a hydrodynamic diameter of ∼100 nm, negative surface charge, and strong retention of the photosensitizer’s spectral profile. The iron oxide nanoparticles (20–30 nm) exhibited efficient magnetic heating potential, reaching 42 °C within 5.5 min under an alternating field (418 kHz, 12 kA·m–1), indicating suitability for future exploration in magnetic hyperthermia applications. While MNE/Ery maintained high biocompatibility toward healthy cells (HDFn and PNT2), it induced a potent light-triggered cytotoxic response in PC-3 prostate cancer cells. Upon irradiation, the platform delivered a robust, dose-dependent therapeutic effect even at conservative fluences, driven by the combination of maghemite-induced oxidative stress (ferroptosis) and erythrosine-mediated ROS generation. These findings position the MNE/Ery system as a promising nanotechnological platform for PDT with an intrinsic iron-mediated chemotherapeutic effect, with additional potential for future magnetic hyperthermia-based applications.