Ru(II)-modified TiO2 nanoparticles for hypoxia-adaptive photo-immunotherapy of oral squamous cell carcinoma

The alternations in the hypoxic and immune microenvironment are closely related to the therapeutic effect and prognosis of oral squamous cell carcinoma (OSCC). Herein, a new nanocomposite, TiO2@Ru@siRNA is con-structed from a ruthenium-based photosensitizer (Ru) modified-TiO2 nanoparticles (NPs) loaded with siRNA of hypoxia-inducible factor-1 alpha (HIF-1 alpha). Under visible light irradiation, TiO2@Ru@siRNA can elicit both Type I and Type II photodynamic effects, which causes lysosomal damage, HIF-1 alpha gene silencing, and OSCC cell elimination efficiently. As a consequence of hypoxia relief and pyroptosis induction, TiO2@Ru@siRNA reshapes the immune microenvironment by downregulation of key immunosuppressive factors, upregulation of immune cytokines, and activation of CD4(+) and CD8(+ )T lymphocytes. Furthermore, patient-derived xenograft (PDX) and rat oral experimental carcinogenesis models prove that TiO2@Ru@siRNA-mediated photodynamic therapy significantly inhibits the tumor growth and progression, and markedly enhances cancer immunity. In all, this study presents an effective hypoxia-adaptive photo-immunotherapeutic nanosystem with great potential for OSCC prevention and treatment.

Automated summary

The new nanocomposite TiO2@Ru@siRNA has potential therapeutic effects on oral squamous cell carcinoma by reshaping the immune microenvironment through downregulating immunosuppressive factors, upregulating immune factors, and activating immune cells.