Bioorthogonal Surface-Edited Exosomes for Targeted Multimodal Imaging and Synergic Chemophototherapy of Oral Cancer

The highly invasive and infiltrative nature of oral cancer blurs the boundary between tumor and normal tissue. The study aimed to develop a targeted nanodrug delivery system utilizing natural biomaterial functionalities to improve the accuracy of oral cancer diagnosis and treatment. In this study, we synthesized RGD-modified exosomes (RGD-EXO) as a targeted nanodrug delivery system to load a coordination compound of indocyanine green and cisplatin (ICG-DDP), collectively known as ID@RGD-EXO, aiming to achieve multimodal imaging and synergistic chemophototherapy for oral cancer. The fluorescence intensity of ID@RGD-EXO is significantly increased compared to ICG. ID@RGD-EXO demonstrated promising potential for noninvasive fluorescence, photoacoustic, and infrared thermal imaging, enabling the comprehensive visualization of oral cancer’s structural and molecular characteristics for precise diagnosis. Laser irradiation-mediated temperature assists in breaking the ICG-DDP coordination bond and destabilizing the exosome membrane, enabling faster site-specific release of DDP to mitigate systemic toxicity of chemotherapy. ICG-mediated phototherapy and low-dose DDP-mediated chemotherapy demonstrated a strong synergistic antitumor effect, significantly improving the therapeutic outcomes for oral cancer. Furthermore, we utilized ID@RGD-EXO to effectively trace metastatic sentinel lymph nodes (SLN), showcasing its strong aggregation, excellent optical properties, enhanced photothermal effect, outstanding biocompatibility, and minimal toxicity. An advanced, low-toxicity nanomedical drug delivery system has been engineered to transport FDA-approved photoreactive and chemical drugs for precise diagnosis, synergistic chemophototherapy, as well as for tracing and ablating metastatic lymph nodes in oral cancer. This groundbreaking research holds great promise for clinical implementation.