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Folate receptor-targeted RNAi nanoparticles for silencing STAT3 in tumor-associated macrophages and tumor cells.
Nanomedicine: Nanotechnology, Biology and Medicine ( IF 4.2 ) Pub Date : 2020-02-18 , DOI: 10.1016/j.nano.2020.102173 Jing Chen 1 , Yushun Dou 1 , Yue Tang 1 , Xinru Zhang 1
Nanomedicine: Nanotechnology, Biology and Medicine ( IF 4.2 ) Pub Date : 2020-02-18 , DOI: 10.1016/j.nano.2020.102173 Jing Chen 1 , Yushun Dou 1 , Yue Tang 1 , Xinru Zhang 1
Affiliation
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We developed a STAT3 silencing siRNA to both tumor cells and M2 macrophages. The dual-targeting system prepared by electronic self-assembly was composed of folic acid-conjugated carboxymethyl chitosan for targeting and cationic chitosan derivatives for siRNA package. The effects of siRNA delivery was investigated in M2 macrophages and Lewis lung cancer cells (LLC). Due to the enhanced delivery efficiency, the dual-targeting delivery system exhibited a higher efficacy compared with non-targeting nanoparticles, resulting in a dramatically reduction of STAT3 expression in both cells, and a successful shift from M2 phenotypes (pro-tumor) to M1 phenotypes (anti-tumor) for macrophages. Additionally, the influence of the nanoparticles on LLC cells co-cultured with M2 macrophages was also investigated. The increased apoptosis and inhibition of proliferation of LLC cells were observed. In vivo therapeutic effect was also evaluated in s.c. tumor models, tumor growth was effectively inhibited and the level of M2 macrophages in tumor tissues was dramatically reduced.
中文翻译：
以叶酸受体为靶标的RNAi纳米颗粒可沉默与肿瘤相关的巨噬细胞和肿瘤细胞中的STAT3。
我们开发了一种针对肿瘤细胞和M2巨噬细胞的STAT3沉默siRNA。电子自组装制备的双靶向系统由叶酸偶联的羧甲基壳聚糖用于靶向和阳离子壳聚糖衍生物用于siRNA包装组成。在M2巨噬细胞和Lewis肺癌细胞（LLC）中研究了siRNA传递的影响。由于提高了递送效率，与非靶向纳米颗粒相比，双重靶向递送系统显示出更高的功效，从而导致两种细胞中STAT3表达的显着降低，并成功地从M2型（肿瘤前型）转变为M1型巨噬细胞的表型（抗肿瘤）。此外，还研究了纳米颗粒对与M2巨噬细胞共培养的LLC细胞的影响。观察到LLC细胞的凋亡增加和增殖抑制。还在sc肿瘤模型中评估了体内治疗效果，有效地抑制了肿瘤生长并且显着降低了肿瘤组织中M2巨噬细胞的水平。
更新日期：2020-02-20
中文翻译：
以叶酸受体为靶标的RNAi纳米颗粒可沉默与肿瘤相关的巨噬细胞和肿瘤细胞中的STAT3。
我们开发了一种针对肿瘤细胞和M2巨噬细胞的STAT3沉默siRNA。电子自组装制备的双靶向系统由叶酸偶联的羧甲基壳聚糖用于靶向和阳离子壳聚糖衍生物用于siRNA包装组成。在M2巨噬细胞和Lewis肺癌细胞（LLC）中研究了siRNA传递的影响。由于提高了递送效率，与非靶向纳米颗粒相比，双重靶向递送系统显示出更高的功效，从而导致两种细胞中STAT3表达的显着降低，并成功地从M2型（肿瘤前型）转变为M1型巨噬细胞的表型（抗肿瘤）。此外，还研究了纳米颗粒对与M2巨噬细胞共培养的LLC细胞的影响。观察到LLC细胞的凋亡增加和增殖抑制。还在sc肿瘤模型中评估了体内治疗效果，有效地抑制了肿瘤生长并且显着降低了肿瘤组织中M2巨噬细胞的水平。
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