Ligand‐Engineered Chiral Gold Nanocluster‐Based Optical Nanoprobes for Photo‐Immune Treatment of Nasopharyngeal Carcinoma

ABSTRACT The emergence of near‐infrared (NIR) optical probes has opened new opportunities for tumor diagnosis and therapy, particularly in nasopharyngeal carcinoma (NPC). In this study, gold nanoclusters (AuNCs) are prepared using various thiol ligands, with structural and surface modifications introducing chiral characteristics to enhance their immune regulatory capacity. Specifically, L‐cysteine‐modified Au 25 nanoclusters with excellent biocompatibility and strong chiral signals exhibit the ability to activate immune responses, complementing their inherent optical properties for imaging‐guided photothermal and photodynamic therapy. To overcome the limitations of rapid metabolism due to the ultrasmall size of AuNCs, they are loaded into mesoporous silica nanoparticles and conjugated with NPC‐targeting peptides, creating a composite nanoprobe with prolonged circulation and improved tumor targeting. In vitro studies indicate efficient uptake of the nanoprobe by NPC cells and significant photothermal and photodynamic effects under laser irradiation, leading to effective tumor cell killing. In vivo experiments in NPC‐bearing mouse models reveal enhanced tumor accumulation, strong imaging signals, and remarkable therapeutic efficacy, with tumors being effectively suppressed and no major side effects observed. These results highlight the great potential of AuNCs‐based optical nanoprobes for precise tumor diagnosis, imaging, and synergistic therapy, offering significant implications for their broader application in cancer treatment.