Inhibition of metastasis and growth of breast cancer by pH-sensitive poly (β-amino ester) nanoparticles co-delivering two siRNA and paclitaxel
Inhibition of metastasis and growth of breast cancer by pH-sensitive poly (β-amino ester) nanoparticles co-delivering two siRNA and paclitaxel
复制标题
DOI：
10.1016/j.biomaterials.2015.01.049
复制
发表时间：
2015-04-01
期刊：
影响因子：
14
通讯作者：
Li, Yaping
中科院分区：
文献类型：
--
作者：
Tang, Shan;Yin, Qi;Li, Yaping
乳腺癌是危害女性健康的最大杀手，而转移则是导致治疗失败的罪魁祸首，增加了复发率。本论文以两种新型两亲性聚合物polyethyleneimine-block-poly[(1，4-butanediol)-diacrylate-P-5-hydroxyamylamine](PEI-PDHA)和聚乙烯glycol-block-poly1(1，4-butanediol)-diacrylate-0-5-hydroxyamylamine](PEGPDHA)为原料，通过自组装的方法，设计并构建了一种新型的复合纳米粒子，负载两种siRNA(Snail siRNA和Twist siRNA)和紫杉醇。实验结果表明，在4T1荷瘤小鼠模型中，PEI-PDHA/PEG-PDHAIPTX/siSna/siTwi复合纳米粒(PPSTs)静脉给药后可提高PTX和siRNA在肿瘤中的蓄积和滞留，同时对肿瘤的生长和转移具有较强的抑制作用。结果发现，siSna和siTwi联合传递比单独传递siRNA具有更显著的抗转移作用，因为同时抑制了癌细胞的运动和细胞外基质的降解。因此，PPSTs有望成为转移性乳腺癌有效治疗的联合载体。(C)2015爱思唯尔有限公司。保留所有权利。
Breast cancer is the most vicious killer for women's health, while metastasis is the main culprit, which leads to failure of treatment by increasing relapse rate. In this work, a new complexes nanoparticles loading two siRNA (Snail siRNA (siSna) and Twist siRNA (siTwi)) and paclitaxel (PTX) were designed and constructed using two new amphiphilic polymer, polyethyleneimine-block-poly[(1,4-butanediol)-diacrylate-P-5-hydroxyamylamine] (PEI-PDHA) and polyethylene glycol-block-poly1(1,4-butanediol)-diacrylate-0-5-hydroxyamylamine] (PEG-PDHA) by self-assembly. The experimental results showed that in the 4T1 tumor-bearing mice models, PEI-PDHA/PEG-PDHAIPTX/siSna/siTwi) complex nanoparticles (PPSTs) raised the accumulation and retention of both PTX and siRNA in tumor after administrated intravenously, resulted in the strong inhibition of the tumor growth and metastasis simultaneously. It was found that co-delivery of siSna and siTwi had more significant anti-metastasis effect than delivering a single siRNA, as a result of simultaneously inhibiting the motility of cancer cells and degradation of ECM. Therefore, PPSTs could be a promising co-delivery vector for effective therapy of metastatic breast cancer. (C) 2015 Elsevier Ltd. All rights reserved.