Early phago-/endosomal escape of platinum drugs via ROS-responsive micelles for dual cancer chemo/immunotherapy.

Abstract

Recent studies have indicated that cancer treatment based on immunotherapy alone is not viable. Combined treatment with other strategies is required to achieve the expected therapeutic effect. Reactive oxygen species (ROS) play an important role in regulating cancer cells and the tumor microenvironment, even in immune cells. However, rigorous regulation of the ROS level within the entire tumor tissue is difficult, limiting the application of ROS in cancer therapy. Therefore, we design an early phago-/endosome-escaping micelle that can release platinum-based drugs into the cytoplasm of macrophages and cancer cells, thereby enhancing the ROS levels of the entire tumor tissue; inducing apoptosis of cancer cells, down-regulation of CD47 expression of cancer cells, polarization of M1 macrophages, and phagocytosis of cancer cells by M1 macrophages; and achieving the dual effect of chemotherapy and macrophage-mediated immunotherapy.