Self-assembled tetrahedral framework nucleic acid mediates tumor-associated macrophage reprogramming and restores antitumor immunity

被引:14
|
作者
Qian, Husun [1 ]
Zhou, Ting [1 ]
Fu, Yixin [1 ]
Guo, Minkang [2 ]
Yang, Wu [2 ]
Zhang, Dian [1 ]
Fang, Wenli [1 ]
Yao, Mengli [1 ]
Shi, He [1 ]
Chai, Chengsen [1 ]
Cheng, Wei [3 ]
Ding, Shijia [1 ]
Chen, Tingmei [1 ]
机构
[1] Chongqing Med Univ, Coll Lab Med, Minist Educ, Key Lab Clin Lab Diagnost, Chongqing 400016, Peoples R China
[2] Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped, Chongqing 400016, Peoples R China
[3] Chongqing Med Univ, Affiliated Hosp 1, Ctr Clin Mol Med Detect, Chongqing 400016, Peoples R China
来源
MOLECULAR THERAPY-NUCLEIC ACIDS | 2022年 / 27卷
基金
中国国家自然科学基金;
关键词
SIRNA; CANCER; PI3K-GAMMA; DNA; NANOPARTICLES; POLARIZATION; CHALLENGES; DIVERSITY; DELIVERY; CELLS;
D O I
10.1016/j.omtn.2021.12.036
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
There is increasing interest in depleting or repolarizing tumorassociated 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 M1 phenotype polarization with increased proinflammatory cytokine secretion and NF-KB signal pathway activation, which 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.
引用
收藏
页码:763 / 773
页数:11
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