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

  • Biomaterials. 2022 Oct:289:121757. doi: 10.1016/j.biomaterials.2022.121757.
Jia-Ying Zhou  1 ,  Wen-Jin Wang  2 ,  Chen-Yu Zhang  1 ,  Yu-Yi Ling  2 ,  Xiao-Jing Hong  1 ,  Qiao Su  3 ,  Wu-Guo Li  3 ,  Zong-Wan Mao  4 ,  Bin Cheng  5 ,  Cai-Ping Tan  6 ,  Tong Wu  7
Affiliations
  • 1. Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, 510055, PR China; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510080, PR China.
  • 2. MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen University, Guangzhou, 510006, PR China.
  • 3. Animal Experiment Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China.
  • 4. MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen University, Guangzhou, 510006, PR China. Electronic address: [email protected].
  • 5. Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, 510055, PR China; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510080, PR China. Electronic address: [email protected].
  • 6. MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen University, Guangzhou, 510006, PR China. Electronic address: [email protected].
  • 7. Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, 510055, PR China; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510080, PR China. Electronic address: [email protected].
PMID: 36058028 DOI: 10.1016/j.biomaterials.2022.121757
Abstract

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 constructed from a ruthenium-based Photosensitizer (Ru) modified-TiO2 nanoparticles (NPs) loaded with siRNA of hypoxia-inducible factor-1α (HIF-1α). Under visible light irradiation, TiO2@Ru@siRNA can elicit both Type I and Type II photodynamic effects, which causes lysosomal damage, HIF-1α 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.

Keywords
Hypoxia adaptation; Oral squamous cell carcinoma; Photo-immunotherapy; Ruthenium; Titanium dioxide.
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