A nanoformulation for immunosuppression reversal and broad-spectrum self-amplifying antitumor ferroptosis-immunotherapy

  • Biomaterials. 2023 Jan:292:121936. doi: 10.1016/j.biomaterials.2022.121936.
Qunfang Yang  1 ,  Tao Liu  1 ,  Haiping Zheng  2 ,  Zechen Zhou  1 ,  Yan Huang  1 ,  Honglin Jia  3 ,  Shixiang Fu  4 ,  Xuan Zhang  1 ,  Haigang Zhang  1 ,  Ya Liu  1 ,  Xiaohong Chen  5 ,  Wenjun Shan  6
Affiliations
  • 1. Department of Pharmacology, College of Pharmacy and Laboratory Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, PR China.
  • 2. School of Medicine, Xiamen University, Xiamen, 361102, PR China.
  • 3. Department of Dermatology, Army Special Medical Center, Army Medical University (Third Military Medical University), Chongqing, 400038, PR China.
  • 4. Teaching and Research Office of Field Internal Medicine, Department of Battlefield First Aid and Medicine, The NCO School of Army Medical University, Shijiazhuang, 050085, PR China.
  • 5. Department of Pharmacology, College of Pharmacy and Laboratory Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, PR China. Electronic address: [email protected].
  • 6. Department of Pharmacology, College of Pharmacy and Laboratory Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, PR China. Electronic address: [email protected].
PMID: 36502663 DOI: 10.1016/j.biomaterials.2022.121936
Abstract

The efficacy of immunotherapy combined with Other therapeutic modalities in the management of Cancer has been extensively studied. However, no effective strategy to improve the antitumor effects of immunotherapy at the tumor site has been developed. In this study, we describe a nanoformulation (CP) that integrates ferroptosis-inducing cannabinoid nanoparticles with immunostimulatory Poly(I:C) to enhance antitumor immune responses by activating ferroptosis-immunotherapy pathways. The results indicated that CP nanoformulation effectively induced Ferroptosis, cellular immunogenic death, and anti-tumor immune responses which initiate T cell responses leading to the inhibition of established tumors. In addition, CP nanoformulations reversed the tumor immunosuppressive microenvironment and promoted tumor Ferroptosis. These results indicated that the self-amplifying nanoformulation may be an effective strategy for broad-spectrum Cancer Immunotherapy.

Keywords
Cannabinoid; Ferroptosis; Immunogenic cell death; Immunotherapy; PD-L1; Poly(I:C).
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