GSH depletion liposome adjuvant for augmenting the photothermal immunotherapy of breast cancer

Sci Adv. 2020 Sep 2;6(36):eabc4373. doi: 10.1126/sciadv.abc4373. Print 2020 Sep.

Abstract

The high redox level of tumor microenvironment inhibits the oxidation treatment and the immune response. Here, we innovatively develop maleimide liposome (ML) adjuvants to promote immunogenic cell death (ICD) induction and dendritic cells (DCs) maturation by glutathione (GSH) depletion for augmenting the photothermal immunotherapy of breast cancer. The ML effectively depletes the intracellular GSH and up-regulates reactive oxygen species (ROS) in both tumor cells and DCs. In tumor cells, the ROS boosted the ABTS·+ production to activate photothermal-induced ICD. In DCs, it relieved the immunosuppression, promoting DC maturation (57%) and antigen presenting. As a result of the ML assistant, the therapeutic systems improved the infiltration of CD8+ T cells to 53% in tumor tissues, eliciting strong abscopal effect and antimetastasis effect. The MLs were believed to be a superior candidate of adjuvants for enhancing immune response and cancer therapeutic efficacy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms* / therapy
  • CD8-Positive T-Lymphocytes
  • Cell Line, Tumor
  • Female
  • Glutathione
  • Humans
  • Immunotherapy
  • Liposomes*
  • Reactive Oxygen Species
  • Tumor Microenvironment

Substances

  • Liposomes
  • Reactive Oxygen Species
  • Glutathione