Ly6k-Targeted Nanoparticles For Therapy In Head And Neck Cancer

This study aimed to identify a tumor-specific biomarker for head and neck squamous cell carcinoma (HNSCC) and develop multifunctional nanoparticles to enable precise photothermal ablation of primary tumors and fluorescence-guided resection of metastatic lymph nodes. Transcriptomic data from GEO (GSE181919) and TCGA databases were analyzed to screen candidate biomarkers. LY6K, a membrane-specific protein overexpressed in HSC-3 cells, was selected for targeted nanoparticle design. Aggregation induced emission (AIE) nanoparticles (LY6K@MTT-oCB NPs) were synthesized and characterized. In vitro studies evaluated cellular targeting, photothermal conversion efficiency, and cytotoxicity. BALB/c nude mice bearing orthotopic tongue tumors received intravenous nanoparticle injections, followed by 10-minute near-infrared-II (NIR-II) irradiation for photothermal therapy. Metastatic lymph nodes were identified via real-time NIR-II fluorescence imaging. Single-cell analysis revealed high expression of LY6K, DSC2, and TK1 in tumor cells, with LY6K specifically overexpressed on the cell membrane of HSC-3 cells. LY6K-targeted nanoparticles (LY6K@MTT-oCB NPs) demonstrated superior membrane targeting and photothermal ablation effects in vitro. In BALB/c nude mouse models, intravenous injection of LY6K@MTT-oCB NPs followed by 10-minute photothermal treatment of primary tumors resulted in significant tumor ablation. Additionally, near-infrared-II fluorescence-guided surgery precisely indicated metastatic lymph nodes with 100% accuracy. LY6K is a promising biomarker for HNSCC tumor cells. LY6K-targeted AIE nanoparticles exhibit excellent potential for photothermal therapy and fluorescence-guided surgery in HNSCC management.