期刊
BIOMATERIALS
卷 289, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2022.121757
关键词
Titanium dioxide; Ruthenium; Photo-immunotherapy; Oral squamous cell carcinoma; Hypoxia adaptation
资金
- Science and Technology Planning Project of Guangzhou, China [202206080009]
- Sci-ence and Technology Planning Project of Guangdong Province, China [2018B030317001]
- National Natural Science Foun-dation of China [22022707, 22177142, 21837006]
- Fundamental Research Funds for the Central Universities
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.
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.
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