Abstract
To address the severe side effects of radiotherapy, high recurrence and metastasis rates, and the limited efficacy of single-mode phototherapy in treating nasopharyngeal carcinoma (NPC), this study reports the development of dumbbell-shaped composite optical nanoprobes enabling multimodal optical imaging-guided NIR-II photothermal-catalytic-immuno synergistic therapy. The nanoprobes consist of platinum nanocluster (PtNCs)-tipped gold nanorods (AuNRs) with surface-loaded indocyanine green (ICG) and NPC-targeting peptides (APINs), that exhibit excellent NIR-II absorption properties, photothermal conversion efficiency, and photoacoustic imaging capability. Moreover, the plasmonic resonance effect of AuNRs enhances the catalytic activity of PtNCs at both ends of the AuNR, promoting the generation of reactive oxygen species and thereby synergistically inducing tumor cell destruction. The APINs can be efficiently internalized by NPC cells, present superior biocompatibility, and effectively induce cell killing under 1064 nm laser irradiation. Further in vivo experiments validate the NPC-targeting multimodal imaging capability and tumor inhibition is achieved post treatments, accompanied by the induction of immunogenic cell death. At 18 days post-administration, NPC-xenografted tumor recurrence and metastasis are significantly suppressed. This approach offers a new optical therapeutic model for precise NPC theranostics, with potential clinical application values.