Chemoimmunological Cascade Cancer Therapy Using Fluorine Assembly Nanomedicine
Qingyan Zhang, Pengkai Wu, Jicheng Wu, Hao Shou, Xinliang Ming, Shuqi Wang, Ben Wang
Abstract
Classical chemotherapeutic drugs may cause immunogenic cell death (ICD), followed by activating CD8 + T cells to promote cell-mediated antitumor immune responses. However, CD8 + T cells become exhausted due to tumor antigens’ continuous stimulation, creating a major obstacle to effectively suppressing tumor growth and metastasis. Here, we develop an approach of chemo-gene combinational nanomedicine to bridge and reprogram chemotherapy and immunotherapy. The dually loaded nanomedicine induces ICD in tumor cells through doxorubicin and reverses the antitumor effects of exhausted CD8 + T cells through the small interfering RNA. The synergistic chemo-gene and fluorine assembly nanomedicine enriched in reactive oxygen species and acid-sensitive bonds results in enhanced cancer immunotherapy to inhibit tumor growth and the lung metastasis of breast cancer in a mouse model of breast cancer and melanoma. This study provides an efficient strategy and insights into chemoimmunological cascade therapy for combating malignant metastatic tumors.