Immunotherapy In Hnscc Through Hme Delivery Of Sipd-1

Immunotherapy has demonstrated promising potential for the treatment of head and neck squamous cell carcinoma (HNSCC); however, its clinical efficacy remains limited due to immune checkpoint-mediated immunosuppression. A novel siPD-1 delivery system, HME-siPD-1, was developed by fusing siPD-1-loaded lipid nanoparticles (LNPs) with a hybrid nanovaccine (Hy-M-Exo) and characterized for size, morphology, protein content, fusion efficiency, siPD-1 loading, and release. Cytotoxicity and hemocompatibility were assessed using CCK-8 and hemolysis assays.The binding of fluorescently labeled HME-siPD-1 to T cells and its PD-1 silencing effect were analyzed via confocal microscopy and flow cytometry. IL-2 and IFN-γ levels in serum were measured by ELISA. Draining lymph nodes and spleens were collected for flow cytometric analysis of PD-1 expression and CTL differentiation.A subcutaneous HNSCC model was established in 6–8-week-old female C3H mice (n = 5/group) to evaluate therapeutic efficacy. Tumor volume and body weight were monitored, with defined endpoint criteria. ELISPOT detected IL-2-secreting splenocytes, and tumor-infiltrating lymphocytes and PD-1 expression were analyzed by flow cytometry. Major organs were stained with H&E to assess toxicity. HME-siPD-1 combines efficient lymph node targeting, potent immunostimulatory capacity, and effective PD-1 silencing. HME-siPD-1 exhibited significant therapeutic efficacy in a mouse model of HNSCC. These findings highlight the clinical potential of HME-siPD-1 as a promising strategy for antitumor immunotherapy.