Magnetically-guided phototherapy using cysteine-modified FePt nanoparticles synthesized under mild aqueous conditions

Although photodynamic therapy (PDT) and photothermal therapy (PTT) offer minimally invasive treatment modalities, their clinical applications remain limited by poor tumor accumulation of photoactive agents and restricted light penetration. Iron-platinum nanoparticles (FePtNPs) have attracted considerable attention as phototherapeutic materials because of their magnetic responsiveness and their ability to generate both reactive oxygen species (ROS) and heat upon light irradiation. However, FePtNPs are synthesized under high-temperature organic conditions, raising concerns regarding their scalability and biocompatibility. Here, we develop cysteine-modified FePt nanoparticles (Cys-FePtNPs) using mild aqueous condition at 60 °C. Cysteine coordination enables stable nanoparticle formation in water, yielding well-dispersed, magnetically responsive particles. Cys-FePtNPs showed laser power-dependent therapeutic effects. Under low-power irradiation, the nanoparticles induce significant cytotoxicity without substantial temperature elevation, indicating a predominantly reactive oxygen species-mediated, nonthermal mechanism. At higher irradiation power, photothermal effects become prominent, demonstrating switchable PDT-like and PTT activities within a single platform. In a melanoma-bearing mouse model, external magnetic guidance enhances tumor accumulation and improves light-induced tumor growth inhibition. These findings demonstrate that FePtNPs synthesized under mild aqueous conditions enable magnetically guided, mechanism-switchable phototherapy, offering a promising strategy to address the current delivery and therapeutic limitations in cancer treatment.