2. Academic Validation
  3. MnO2-melittin nanoparticles serve as an effective anti-tumor immunotherapy by enhancing systemic immune response

MnO2-melittin nanoparticles serve as an effective anti-tumor immunotherapy by enhancing systemic immune response

  • Biomaterials. 2022 Sep;288:121706. doi: 10.1016/j.biomaterials.2022.121706.
Shupei Tang 1,  Lan Zhou 2,  Haiyang He 2,  Liwei Cui 3,  Zhicheng Ren 4,  Yuhang Tai 5,  Zhunyi Xie 2,  Yi Cao 2,  Dongwei Meng 2,  Qiuli Liu 1,  Yuzhang Wu 6,  Jun Jiang 7,  Xinyuan Zhou 8
Affiliations

Affiliations

  • 1 Department of Urology, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.
  • 2 Institute of Immunology, Third Military Medical University, Chongqing, 400038, China.
  • 3 Institute of Immunology, Third Military Medical University, Chongqing, 400038, China; Department of Tropical Medicine and Infectious Diseases, Hainan Hospital of PLA General Hospital, Hainan, 572000, China.
  • 4 Department of Medical Engineering, The 955th Hospital of PLA, Xizang, 854000, China.
  • 5 Department of Proctology, First People's Hospital of Liangshan Yi Autonomous Prefecture, Sichuan, 615099, China.
  • 6 Institute of Immunology, Third Military Medical University, Chongqing, 400038, China. Electronic address: wuyuzhang@yahoo.com.
  • 7 Department of Urology, Daping Hospital, Third Military Medical University, Chongqing, 400042, China. Electronic address: jiangjun_64@163.com.
  • 8 Institute of Immunology, Third Military Medical University, Chongqing, 400038, China. Electronic address: xinyuanzhou@tmmu.edu.cn.
PMID: 35953328 DOI: 10.1016/j.biomaterials.2022.121706
Abstract

Cancer vaccines are viewed as a promising immunotherapy to eradicate malignant tumors and aim to elicit the patients' own tumor-specific immune response against tumor cells. However, few Cancer vaccines have been applied due to the low immunogenicity of antigen and invalidation of adjuvant. Herein, we designed a tumor microenvironment (TME) responsive MnO2-melittin nanoparticles (M-M NPs). The M-M NPs consumed glutathione and produced •OH via Fenton-like reaction in the mimic TME, specifically caused tumor cell death in vitro, activated cGAS-STING pathway in vitro and promoted the maturation of antigen-presenting cells in vitro and in vivo to elicit systemic anti-tumor immune response including the augmentation of tumor-specific T cells and more productions of pro-inflammatory cytokines and chemokines, which all were stronger than MnO2 NPs and melittin. The anti-tumor effects of M-M NPs were evaluated in three subcutaneous tumor models and the B16-F10 lung metastasis model and the tumor growth and lung metastasis were more obviously inhibited in the M-M NPs treated mice, compared with MnO2 NPs and melittin treatments. More importantly, only M-M NPs promoted the MHC-I cross-dressing by dendritic cells to prime tumor-specific CD8+ T cells and remarkably suppressed the growth of left tumors if express cognate antigen while treating on the right in the bilateral tumor model. Our findings proposed a strategy to enhance the Cancer vaccine efficiency which showed great therapeutic effect on tumor immunotherapy.

Keywords

Anti-Tumor immunotherapy; Systemic immune response; Tumor microenvironment; Tumor nanovacine; Whole cell antigen.

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