巨噬细胞极化
促炎细胞因子
癌症研究
肿瘤微环境
CpG站点
癌症免疫疗法
免疫疗法
免疫系统
重编程
肿瘤相关巨噬细胞
化学
生物
巨噬细胞
细胞生物学
免疫学
炎症
DNA甲基化
细胞
体外
生物化学
基因表达
基因
作者
Husun Qian,Ting Zhou,Yixin Fu,Minkang Guo,Yang Wu,Dian Zhang,Wenli Fang,Mengli Yao,He Shi,Chengsen Chai,Wei Cheng,Shijia Ding,Tingmei Chen
标识
DOI:10.1016/j.omtn.2021.12.036
摘要
There is increasing interest in depleting or repolarizing tumor-associated macrophages (TAMs) to generate a proinflammatory effect. However, TAMs usually display an immunosuppressive M2-like phenotype in the tumor microenvironment. Apparently, developing a macrophage-targeting delivery system with immunomodulatory agents is urgent. In this study, an efficient siRNA and CpG ODNs delivery system (CpG-siRNA-tFNA) was prepared with nucleic acid stepwise self-assembled. The tFNA composed of CpG ODNs and siRNA showed a higher stability and an enhanced cellular uptake efficiency. Moreover, the CpG-siRNA-tFNA effectively reprogrammed TAMs toward M1 phenotype polarization with increased proinflammatory cytokine secretion and NF-κB signal pathway activation, which triggers dramatic antitumor immune responses. Additionally, the CpG-siRNA-tFNA exhibited superior antitumor efficacy in a breast cancer xenograft mouse model without obvious systemic side effects. Taken together, CpG-siRNA-tFNA displayed greatly antitumor effect by facilitating TAM polarization toward M1 phenotypes in favor of immunotherapy. Hence, we have developed an efficient therapeutic strategy with immunomodulatory agents for clinical applications.
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