AS1411 Aptamer-Decorated Biodegradable Polyethylene Glycol-Poly(lactic-co-glycolic acid) Nanopolymersomes for the Targeted Delivery of Gemcitabine to Non-Small Cell Lung Cancer In Vitro
AS1411 Aptamer-Decorated Biodegradable Polyethylene Glycol-Poly(lactic-co-glycolic acid) Nanopolymersomes for the Targeted Delivery of Gemcitabine to Non-Small Cell Lung Cancer In Vitro
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DOI：
10.1016/j.xphs.2016.02.021
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发表时间：
2016-05-01
影响因子：
3.8
通讯作者：
Hadizadeh, Farzin
中科院分区：
文献类型：
--
作者：
Alibolandi, Mona;Ramezani, Mohammad;Hadizadeh, Farzin
分子靶向给药系统代表了治疗不同癌症的新的治疗策略。在本研究中，我们开发了负载吉西他滨（GEM）的AS 1411适配体表面修饰的聚乙二醇-聚（乳酸-羟基乙酸）纳米聚合物体（Apt-GEM-NP），以靶向核仁素过表达的非小细胞肺癌（NSCLC; A549）。制备的Apt-GEM-NP显示出128 +/- 5.23 nm的平均粒径和球形形态，包封率和载量分别为95.32 +/- 2.37%和8.61 +/-0.27%。Apt-GEM-NP具有控释模式。药物在生理条件下的持续释放将大大提高系统的化疗效率。在A549癌细胞中增强的细胞摄取和适体缀合的纳米颗粒（NPs）的细胞毒性明显验证了核仁介导的基于受体的主动靶向。通过流式细胞术和荧光显微镜进一步证实了核仁蛋白介导的靶向聚合物NP的内化。3-（4，5-二甲基噻唑-2-基）-2，5-二苯基四唑溴化物测定清楚地显示，由于GEM选择性递送至核仁素过表达癌细胞，AS 1411缀合的NP的细胞增殖抑制作用增强。我们的研究结果表明，在NP表面上的AS 1411适体缀合可能是作为核仁素过表达细胞系的A549的潜在治疗策略。这表明AS 1411-GEM-NP可潜在地用于治疗NSCLC。(C)2016年美国药学协会（R）。爱思唯尔公司出版All rights reserved.
Molecularly targeted drug delivery systems represent a novel therapeutic strategy in the treatment of different cancers. In the present study, we have developed gemcitabine (GEM)-loaded AS1411 aptamer surface-decorated polyethylene glycol-poly(lactic-co-glycolic acid) nanopolymersome (Apt-GEM-NP) to target nucleolin-overexpressing non-small cell lung cancer (NSCLC; A549). The prepared Apt-GEM-NP showed average particle size of 128 +/- 5.23 nm and spherical morphology with encapsulation efficiency and loading content of 95.32 +/- 2.37% and 8.61 +/- 0.27%, respectively. Apt-GEM-NP exhibited a controlled release pattern. A sustained release of drug in physiological conditions will greatly improve the chemotherapeutic efficiency of a system. Enhanced cellular uptake and the cytotoxicity of aptamer-conjugated nanoparticles (NPs) in A549 cancer cells obviously verified nucleolin-mediated receptor-based active targeting. Nucleolin-mediated internalization of the targeted polymeric NP was further confirmed by flow cytometry and fluorescence microscopy. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay clearly showed the enhanced cell proliferation inhibitory effect of AS1411-conjugated NP on account of the selective delivery of GEM to the nucleolin-overexpressing cancer cells. Our results showed that AS1411 aptamer conjugation on the surface of NP could be a potential treatment strategy for A549 as a nucleolin-overexpressing cell line. This suggests that AS1411-GEM-NPs could be potentially used for the treatment of NSCLC. (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.