Synergistic dual photothermal-photodynamic nanoplatforms via BSA-stabilized gold nanospheres for selective melanoma phototherapy

Gold nanospheres (AuNSs) are promising agents for light-triggered cancer therapy, yet their biomedical performance strongly depends on surface chemistry and colloidal stability. Here, we report a multifunctional nanoplatform based on Bovine Serum Albumin (BSA)-coated AuNSs designed to synergistically combine photothermal and photodynamic effects under low-power LED irradiation. Systematic optimization of the BSA coating revealed that a dense protein corona at 225 µM yields highly stable, monodisperse nanosystems with preserved plasmonic features and excellent thermal reproducibility over multiple irradiation cycles. These optimized AuNSs-BSA were further functionalized with Rose Bengal (RB) to obtain hybrid RB-AuNSs-BSA nanoplatforms integrating plasmonic heating with efficient reactive oxygen species (ROS) generation. Under 530 nm irradiation, the hybrid nanoplatforms induced a enhanced oxidative response in melanoma A375 cells, accompanied by significant viability loss and ultrastructural features indicative of mitochondrial and endoplasmic reticulum stress. In contrast, normal HaCaT keratinocytes displayed minimal ROS increases and maintained high viability, demonstrating a clear therapeutic selectivity. Control experiments confirmed that neither BSA coating nor RB loading compromised optical stability or colloidal integrity. Overall, this work establishes RB-AuNSs-BSA as a biocompatible, and LED-activatable nanoplatform capable of dual photothermal-photodynamic action, highlighting its potential for safe and selective melanoma treatment and for broader multimodal theranostic applications.