RHCG-Upregulating Polymeric Nanoparticles for Sensitized Chemotherapy and Immunotherapy in Head and Neck Squamous Cell Carcinoma

Immunotherapy and multifactor-induced chemoresistance for HNSCC are accompanied by a high incidence of adverse side effects. In clinics, it is urgently required to alleviate adverse effects and improve chemosensitivity. The drug delivery system (named TP NPs) based on poly (I:C) was synthesized using poly(ethylene glycol) (PEG) diamine as the shell. The NPs triggered in situ antitumor immune response and effectively enhanced the sensitivity of cancer cells to cisplatin. Meanwhile, TP NPs proved a slow release rate of PIC, and PIC binds to the TLR3 receptor in the cytoplasm, upregulating the tumor suppressor gene RHCG. Furthermore, TP NPs accumulated at the tumor site and triggered antitumor immune activation, including promoting DC maturation and shifting macrophages into M1 macrophages in a xenograft mouse tumor model. TP NPs effectively destroyed the tumors via combinatorial therapy in vitro and in vivo, providing a strategy for head and neck squamous cell carcinoma.