A third-generation rhodium-based nanophotosensitizer for precision photodynamic cancer therapy.

Rhodium-based nanocomposites represent an unexplored class of functional materials with potential in biomedicine. Here, we present RhNPs-MSNs-Tf, a third-generation nanophotosensitizer composed of rhodium nanoparticles (RhNPs) confined within mesoporous silica nanoparticles (MSNs) and surface-modified with transferrin (Tf) to enable receptor-mediated tumor targeting. This represents the first silica-based nanocomposite integrating RhNPs for biomedical applications ever reported in literature. The hybrid structure is obtained through a robust multistep synthetic route and extensively characterized, confirming uniform RhNPs incorporation, preserved mesoporosity, colloidal stability and excellent biocompatibility. Under near-infrared (NIR) irradiation, RhNPs-MSNs-Tf efficiently generates singlet oxygen (1O2). Cellular studies demonstrate selective uptake and light-triggered cytotoxicity in cancer cells, while metabolomic analysis reveals rewiring of oxidative stress and energy metabolism pathways as underlying mechanisms. In vivo evaluation using the chicken chorioallantoic membrane (CAM) model shows significant tumor growth inhibition without apparent systemic toxicity. By combining structural precision, efficient photodynamic response and active targeting capability, RhNPs-MSNs-Tf establishes a versatile, light-activated nanoplatform. These findings highlight the promise of rhodium-based nanocomposites as next-generation functional materials for tumor-selective photodynamic therapy (PDT).