共 13 条
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.
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页码:763 / 773
页数:11
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