Department of Chemistry, University of Massachusetts , 710 North Pleasant Street, Amherst, Massachusetts 01003, United States.
Bioconjug Chem. 2018 Feb 21;29(2):445-450. doi: 10.1021/acs.bioconjchem.7b00768. Epub 2018 Jan 22.
We present here an integrated nanotechnology/biology strategy for cancer immunotherapy that uses arginine nanoparticles (ArgNPs) to deliver CRISPR-Cas9 gene editing machinery into cells to generate SIRP-α knockout macrophages. The NP system efficiently codelivers single guide RNA (sgRNA) and Cas9 protein required for editing to knock out the "don't eat me signal" in macrophages that prevents phagocytosis of cancer cells. Turning off this signal increased the innate phagocytic capabilities of the macrophages by 4-fold. This improved attack and elimination of cancer cells makes this strategy promising for the creation of "weaponized" macrophages for cancer immunotherapy.
我们在此提出了一种癌症免疫治疗的综合纳米技术/生物学策略,该策略使用精氨酸纳米颗粒(ArgNPs)将 CRISPR-Cas9 基因编辑机制递送到细胞中,以生成 SIRP-α敲除巨噬细胞。该 NP 系统有效地共递送了用于编辑的单指导 RNA(sgRNA)和 Cas9 蛋白,以敲除巨噬细胞中阻止癌细胞吞噬的“不要吃我信号”。关闭该信号使巨噬细胞的先天吞噬能力提高了 4 倍。这种提高对癌细胞的攻击和消除能力使这种策略有望用于为癌症免疫治疗创建“武器化”巨噬细胞。