Macrophage Membrane-Camouflaged shRNA and Doxorubicin: A pH-Dependent Release System for Melanoma Chemo-Immunotherapy
Chengli Yang,
Yang Ming,
Kai Zhou,
Ying Hao,
Danrong Hu,
Bingyang Chu,
Xinlong He,
Yun Yang,
Zhiyong Qian
Affiliations
Chengli Yang
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China; Department of Pharmacy, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550000, China
Yang Ming
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China
Kai Zhou
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China
Ying Hao
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China
Danrong Hu
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China
Bingyang Chu
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China
Xinlong He
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China
Yun Yang
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China
Zhiyong Qian
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China
Improving the efficacy of melanoma treatment remains an important global challenge. Here, we combined chemotherapy with protein tyrosine phosphatase nonreceptor type 2(Ptpn2) based immunotherapy in an effort to address this challenge. Short-hairpin RNA (shRNA) targeting Ptpn2 was coencapsulated with doxorubicin (DOX) in the cell membrane of M1 macrophages (M1HD@RPR). The prepared nanoparticles (NPs) were effectively phagocytosed by B16F10 cells and M1 macrophages, but not by M0 macrophages. Hence, NP evasion from the reticuloendothelial system (RES) was improved and NP enrichment in tumor sites increased. M1HD@RPR can directly kill tumor cells and stimulate immunogenic cell death (ICD) by DOX and downregulate Ptpn2. It can promote M1 macrophage polarization and dendritic cell maturation and increase the proportion of CD8+ T cells. M1HD@RPR killed and inhibited the growth of primary melanoma and lung metastatic tumor cells without harming the surrounding tissue. These findings establish M1HD@RPR as a safe multifunctional nanoparticle capable of effectively combining chemotherapy and gene immunotherapies against melanoma.
