Dumbbell-Structured Plasmonic-Enhanced Optical Nanoprobes Boosting Photo-Magnetic-Acoustic Multimodal Imaging-Guided Photodynamic-Photothermal Synergistic Treatment and Immunogenic Death in Nasopharyngeal Carcinoma.

Herein, we report a high-performance optical nanoprobe featuring dumbbell-shaped mesoporous silica-coated gold nanorods, loaded with rare earth-doped gadolinium oxide nanocrystals and photosensitizer indocyanine green, and functionalized with targeting peptides. The nanoprobe exhibits enhanced near-infrared photoluminescence performance while enabling efficient photothermal conversion, photodynamic effect, photoacoustic imaging, and magnetic resonance imaging enhancement. Theoretical simulations demonstrate that the local surface plasmon resonance effect of gold nanorods exerts a significant enhancement on the optical performance of nanoprobes. Moreover, metal atoms play a pivotal role in modulating excited states and enhancing the intersystem crossing of indocyanine green. In vitro experiments confirm that the nanoprobe exhibits favorable biocompatibility and tumor-targeting capacity; under 808 nm laser irradiation, it enables synergistic therapy by generating reactive oxygen species and inducing hyperthermia, with the mechanism underlying synergistic treatment elucidated from both physical and biological perspectives. The nanoprobe facilitates near-infrared photo-magnetic-acoustic-thermal multimodal imaging, achieves efficient photothermal-photodynamic synergistic therapy on tumor-xenografted mice upon the laser irradiation, exerts effective inhibition on tumor growth, and mitigates tumor recurrence by inducing immunogenic cell death. This study offers insights into the design of novel high-performance optical nanoprobes and highlights the application potential of this nanoprobe in the precise diagnosis and synergistic treatment of nasopharyngeal carcinoma.