免疫系统
先天免疫系统
获得性免疫系统
免疫疗法
癌症研究
免疫检查点
脱氧核酶
癌症免疫疗法
化学
生物
细胞生物学
免疫学
生物化学
DNA
作者
Chen Chao,Shiyu Du,Qianglan Lu,Kunguo Liu,Yongchun Pan,Yiqun Jiang,Jingjing Yang,Xin Han,Yujun Song
标识
DOI:10.1016/j.cej.2023.145192
摘要
Targeted manipulation of cytoplasmic double-strand (dsDNA) generation in tumors to activate cGAS-STING signaling remains challenging in antitumor immunity. Herein, we proposed an endogenous tumor-associated microRNAs-triggered theranostic nanosystem for codelivery of Hybridization Chain Reaction (HCR) and DNAzyme systems to achieve robust long-term antitumor immunity based on MnO2-adjuvant nanoparticles. The MnO2 was decomposed into Mn2+ ions in the endosome and thus released HCR and DNAzyme systems. Endogenous miR-21-triggered HCR for dsDNA generation, thereby resulting in cGAS-STING signaling activation. Meanwhile, the DNAzyme system was unlocked and catalyzed respectively via endogenous miR-146a and cofactor Mn2+ ions for gene silencing of programmed cell death ligand 1 (PD-L1) to achieve immune-checkpoint blockade (ICB). The combination of innate immunity based on HCR system and adaptive immune-responses mediated by DNAzyme system acquired robust antitumor immunity and long-term immune effect on distal tumors and pulmonary metastasis in vivo. In summary, this endogenously-responsive nanosystem with self-supplied cytoplasmic dsDNA presents strong antitumor immune activation and provides a long-term immunotherapeutic potential for cancer therapy.
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