Abstract

Osteosarcoma, the most common primary malignant bone tumor in adolescents, faces treatment challenges due to metastasis and chemoresistance. This study developed a novel Au@Rh core–shell nanoparticle system functionalized with indocyanine green (ICG) to overcome hypoxia-limited photodynamic therapy (PDT). Au@Rh nanoparticles were synthesized via wet chemistry and characterized by UV-Vis spectroscopy, TEM, and cyclic voltammetry (CV). The system exhibited a core–shell morphology, well-defined crystalline planes, photothermal conversion and electrocatalytic activity. The Au@Rh nanoparticles (109 nm total size, 90 nm Au core, and 15 nm Rh shell) demonstrated dual functionality: the gold core provided photothermal conversion (a 7 °C temperature increase under NIR irradiation), while the rhodium shell exhibited pH-independent electrocatalytic activity for H2O2 decomposition, generating oxygen to alleviate tumor hypoxia. Crucially, the system showed excellent biocompatibility, with no significant cytotoxicity in both osteosarcoma (HOS) or normal osteoblast (hFOB) cells after 48 h of exposure. When activated by NIR irradiation (808 nm, 16.6 J/cm2), the complete Au@Rh-ICG system achieved selective 67% cytotoxicity in HOS cells versus only 30% in hFOB cells, demonstrating targeted therapeutic efficacy. These results position Au@Rh-ICG as a promising theranostic platform for osteosarcoma treatment, combining enhanced PDT with photothermal therapy while addressing tumor hypoxia.

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