巨噬细胞
钙网蛋白
免疫疗法
CD47型
癌症免疫疗法
癌症研究
免疫系统
吞噬作用
化学
生物
细胞生物学
材料科学
免疫学
体外
生物化学
内质网
作者
Qiaoyi Huang,Miao Su,Liang Zhao,Zhenghai Zhang,Yuxi Zhang,Xianzhu Yang,Jun Wang
出处
期刊:Nano Today
[Elsevier]
日期:2023-06-01
卷期号:50: 101857-101857
被引量:4
标识
DOI:10.1016/j.nantod.2023.101857
摘要
Effectively activating macrophages to 'eat' tumor cells have great potential in cancer immunotherapy. However, tumor cells can express CD47 to evade macrophages, and secrete immunosuppressive factors to polarize macrophages into a pro-tumorigenic M2 phenotype. Herein, PEI-coated Au nanorods with an inherent capability to induce calreticulin (CRT) exposure were prepared and then used to electrostatically adsorb the CRISPR/Cas9 plasmid pH330/sgCD47, generating AuPpH330/sgCD47 nanocomplexes. The efficient induction of CRT exposure by AuPpH330/sgCD47 nanocomplexes provides additional "eat-me" signals to macrophages, especially under a 1064 nm laser. Meanwhile, AuPpH330/sgCD47 nanocomplexes under a 1064 nm laser activated the HSP70 promoter of pH330/sgCD47 to drive CD47 genomic disruption to suppress "don't eat-me" signals. Therefore, AuPpH330/sgCD47 treatment synergistically promoted the macrophage phagocytosis of tumor cells and increased M2-to-M1 macrophage repolarization, which stimulates a potent immune response to inhibit tumor growth and lung metastasis. These HSP70 promoter-driven genetically edited nanoparticles represent a promising strategy for macrophage-mediated cancer immunotherapy.
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