Development of a nano-immunomodulator encapsulating R837 and caffeine for combined radio-/immunotherapy against orthotopic breast cancer

• Published in: Progress in natural science Vol. 30; no. 5; pp. 697 - 706
• Main Authors: Liu, Te-I, Tsai, Yuan-Chung, Wang, Te-Ming, Chang, Siou-Han, Yang, Ying-Chieh, Chen, Hsin-Hung, Chiu, Hsin-Cheng
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2020; Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu City, Taiwan%Department of Radiology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu City, Taiwan
• Subjects: Breast cancer; Combination therapy; Drug delivery; Immunomodulation; Radiotherapy; Drug delivery; Breast cancer; Radiotherapy; Combination therapy; Immunomodulation
• ISSN: 1002-0071
• DOI: 10.1016/j.pnsc.2020.09.014

Immunotherapy is an ascendant approach in cancer treatment. It shows more pronounced effects on killing cancer cells in a specific manner in particular against metastasis more than traditional techniques, such as chemotherapy or surgery. However, tumor immunosuppression limits the response of the immune system to cancer development. In this study, we developed a lipid-based nanocarrier doubly loaded with imiquimod (R837), a toll-like receptor 7 agonist, and caffeine, an adenosine receptor antagonist. This R837/caffeine loaded nanocarrier served as a nano-immunomodulator (RC-nIM) for combination treatment with radiotherapy (RT) against orthotopic breast cancer. RT-induced immunogenic cell death facilitated the production of tumor antigen and elicited the immune response in corporation with R837-medaited activation of antigen-presenting cells (APCs) while RC-nIMs being adopted. Additionally, caffeine, an adenosine analog, can successfully compete with adenosine in the tumor. The tumor-bearing mice that received RT together with RC-nIMs experienced the best antitumor effects and exhibited higher levels of T cells and APCs within the tumor; the growth of secondary tumors was also limited. This work serves as a proof-of-concept study for the development of a new immunotherapy strategy against cancer. [Display omitted] •An R837/caffeine loaded nano-immunomodulator (RC-nIMs) system was developed.•RC-nIMs combined with Radiotherapy (RT) elevated T cell/APC levels in tumors.•RC-nIM/RT treatment showed the best therapeutic outcome for primary and distal tumors.•This work demonstrated a new immunotherapy strategy for cancer treatment.