In vitro and in vivo evaluation of therapy targeting epithelial-cell adhesion-molecule aptamers for non-small cell lung cancer
In vitro and in vivo evaluation of therapy targeting epithelial-cell adhesion-molecule aptamers for non-small cell lung cancer
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DOI：
10.1016/j.jconrel.2015.04.026
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发表时间：
2015-07-10
影响因子：
10.8
通讯作者：
Hadizadeh, Farzin
中科院分区：
文献类型：
--
作者：
Alibolandi, Mona;Ramezani, Mohammad;Hadizadeh, Farzin
治疗性纳米颗粒的靶向、疾病特异性递送显示出用于传递高细胞毒性抗癌剂的美好前景。利用非小细胞肺癌的反应（SK-MES-1和A549细胞系）作为其他癌症类型的代表”，本研究检查了EpCAM-氟嘧啶RNA适体修饰的，DOX负载的，PLGA-b-PEG纳米聚合物体，与上皮细胞粘附分子的细胞外结构域特异性结合。结果表明EpCAM适体缀合的DOX-NP（Apt-DOX-NP）与非靶向DOX-NP相比，显著增强SK-MES-1和A549细胞系中的细胞纳米颗粒摄取，并增加DOX有效载荷的细胞毒性此外，Apt-DOX-NP在携带SK-MES-1非小细胞肺癌异种移植物的裸鼠中表现出更大的肿瘤抑制并降低毒性，通过体重减轻、心脏组织病理学和动物体内存活率测定。单次静脉注射Apt-DOX-NP和DOX-NPs后，SK-MES-1-异种移植裸鼠的肿瘤体积分别比注射生理盐水的对照组减少了60.9%和31.4%，该研究证明了Apt-DOX-NP在非小细胞肺癌治疗应用中的潜在效用。在未来，EpCAM靶向疗法可能在治疗非小细胞肺癌（最常见的肺癌类型）方面发挥关键作用。(C)2015爱思唯尔B. V.保留所有权利。
Targeted, disease-specific delivery of therapeutic nanoparticles shows wonderful promise for transmitting highly cytotoxic anti-cancer agents. Using the reaction of non-small cell lung cancer (SK-MES-1 and A549 cell lines) as representative of other cancer types', the present study examines the effects of EpCAM-fluoropyrimidine RNA aptamer-decorated, DOX-loaded, PLGA-b-PEG nanopolymersomes that bond specifically to the extracellular domain of epithelial-cell adhesion molecules.Results demonstrate that EpCAM aptamer-conjugated DOX-NPs (Apt-DOX-NP) significantly enhance cellular nanoparticle uptake in SK-MES-1 and A549 cell lines and increase the cytotoxicity of the DOX payload as compared with non-targeted DOX-NP (P < 0.05).Additionally, Apt-DOX-NP exhibits greater tumor inhibition in nudemice bearing SK-MES-1 non-small cell lung-cancer xenografts and reduces toxicity, as determined by loss of body weight, cardiac histopathology and animal survival rate in vivo. After a single intravenous injection of Apt-DOX-NP and DOX-NPs, tumor volume decreased 60.9% and 31.4%, respectively, in SK-MES-1-xenograft nude mice compared with members of a saline-injected control group.This study proves the potential utility of Apt-DOX-NP for therapeutic application in non-small cell lung cancer. In the future, EpCAM-targeted therapies might play a key role in treating non-small cell lung cancer, the most common type of lung cancer. (C) 2015 Elsevier B.V. All rights reserved.