Co-delivery of doxorubicin and RNA using pH-sensitive poly (β-amino ester) nanoparticles for reversal of multidrug resistance of breast cancer
Co-delivery of doxorubicin and RNA using pH-sensitive poly (β-amino ester) nanoparticles for reversal of multidrug resistance of breast cancer
复制标题
使用 pH 敏感的聚（β-氨基酯）纳米颗粒共同递送阿霉素和 RNA，用于逆转乳腺癌的多药耐药性
DOI：
10.1016/j.biomaterials.2014.04.025
复制
发表时间：
2014-07-01
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
合适的化疗药物和核酸药物联合给药系统将通过逆转多药耐药性（MDR）为乳腺癌的治疗提供更有效的方法。本工作合成了一种新型两亲性聚（β-氨基酯）聚[（1,4-丁二醇）-二丙烯酸酯-β-5-聚乙烯亚胺]-嵌段-聚[（1,4-丁二醇）-二丙烯酸酯-β-5-羟基戊胺]（PDP-PDHA），以及阿霉素（DOX）和生存素靶向shRNA（shSur）共负载纳米颗粒(PDN) 已准备好。 pH敏感的聚[(1,4-丁二醇)二丙烯酸酯-β-5-羟基戊胺](PDHA)赋予PDNs pH触发的药物释放特性和增强的内/溶酶体逃逸能力，从而提高DOX的细胞毒性和转染效率。 PDN 还增加了 DOX 的积累，下调了 57.7% 的生存素表达，诱导 80.8% 的细胞凋亡，并改变了 MCF-7/ADR 细胞的细胞周期。在MCF-7/ADR荷瘤小鼠模型中，静脉注射后，PDNs使肿瘤组织中DOX和shSur的积累分别增加10.4倍和20.2倍，从而明显抑制肿瘤生长，抑瘤率高达95.9%。 DOX和RNA干扰的结合在克服MDR方面表现出协同作用。因此，PDNs可能成为有效治疗耐药乳腺癌的有前途的共递送载体。 (C) 2014 Elsevier Ltd. 保留所有权利。
An appropriate co-delivery system for chemotherapeutic agents and nucleic acid drugs will provide a more efficacious approach for the treatment of breast cancer by reversing multidrug resistance (MDR). In this work, a new amphiphilic poly (beta-amino ester), poly[(1,4-butanediol)-diacrylate-beta-5-polyethylenimine]-block-poly[(1,4-butanediol)-diacrylate-beta-5-hydroxy amylamine] (PDP-PDHA) was synthesized, and the doxorubicin (DOX) and survivin-targeting shRNA (shSur) co-loading nanoparticle (PDNs) were prepared. The pH-sensitive poly[(1,4-butanediol) diacrylate-beta-5-hydroxy amylamine] (PDHA) endowed PDNs both pH-triggered drug release characteristics and enhanced endo/lysosomal escape ability, thus improving the cytotoxicity of DOX and the transfection efficiency. PDNs also increased the DOX accumulation, down-regulated 57.7% survivin expression, induced 80.8% cell apoptosis and changed the cell cycle in MCF-7/ADR cells. In the MCF-7/ADR tumor-bearing mice models, after administrated intravenously, PDNs raised the accumulation of DOX and shSur in the tumor tissue by 10.4 and 20.2 folds, respectively, resulting in obvious inhibition of the tumor growth with tumor inhibiting rate of 95.9%. The combination of DOX and RNA interference showed synergistic effect on overcoming MDR. Therefore, PDNs could be a promising co-delivery vector for effective therapy of drug resistant breast cancer. (C) 2014 Elsevier Ltd. All rights reserved.