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

Pei-Wei Shueng; Lu-Yi Yu; Hsin-Cheng Chiu; Hui-Ching Chang; Yen-Ling Chiu; Tzu-Yu Kuo; Yu-Wei Yen; Chun-Liang Lo

doi:10.1016/j.biomaterials.2021.121012

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

Biomaterials. 2021 Sep:276:121012. doi: 10.1016/j.biomaterials.2021.121012. Epub 2021 Jul 7.

Authors

Pei-Wei Shueng¹, Lu-Yi Yu², Hsin-Cheng Chiu³, Hui-Ching Chang², Yen-Ling Chiu⁴, Tzu-Yu Kuo², Yu-Wei Yen², Chun-Liang Lo⁵

Affiliations

¹ Division of Radiation Oncology, Far Eastern Memorial Hospital, New Taipei City, 220, Taiwan, ROC; Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan, ROC; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, 112, Taiwan, ROC; Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, 112, Taiwan, ROC.
² Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan, ROC; Department of Biomedical Engineering, National Yang-Ming University, Taipei, 112, Taiwan, ROC.
³ Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, Hsinchu, 300, Taiwan, ROC.
⁴ Graduate Program in Biomedical Informatics and Graduate Institute of Medicine, Yuan Ze University, Taoyuan City, 320, Taiwan, ROC; Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, 100, Taiwan, ROC; Department of Medical Research, Far Eastern Memorial Hospital, New Taipei City, 220, Taiwan, ROC.
⁵ Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan, ROC; Department of Biomedical Engineering, National Yang-Ming University, Taipei, 112, Taiwan, ROC; Center for Advanced Pharmaceutics and Drug Delivery Research, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan, ROC. Electronic address: cllo@ym.edu.tw.

PMID: 34252800
DOI: 10.1016/j.biomaterials.2021.121012

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.

Keywords: Chemotherapy; Immunotherapy; Phago-/endosomal escape; Polymeric micelles; Tumor-associated macrophages.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Immunotherapy
Micelles*
Neoplasms* / drug therapy
Platinum
Reactive Oxygen Species

Substances

Micelles
Reactive Oxygen Species
Platinum