Targeted delivery of doxorubicin to A549 lung cancer cells by CXCR4 antagonist conjugated PLGA nanoparticles
Targeted delivery of doxorubicin to A549 lung cancer cells by CXCR4 antagonist conjugated PLGA nanoparticles
复制标题
DOI：
10.1016/j.ejpb.2014.06.020
复制
发表时间：
2014-10-01
影响因子：
4.9
通讯作者：
Sarisuta, Narong
中科院分区：
文献类型：
--
作者：
Chittasupho, Chuda;Lirdprapamongkol, Kriengsak;Sarisuta, Narong
多柔比星用于治疗多种癌症，但剂量限制性毒性或内在和获得性抗性限制了其在许多类型癌症中的应用。CXCR 4是一种趋化因子受体，与包括肺癌在内的癌症的转移有关。LFC 131是一种CXCR 4-配体结合肽抑制剂，是一种线性型低分子量CXCR 4拮抗剂。在这项研究中，我们研究了使用LFC 131缀合的纳米颗粒靶向递送阿霉素至表达CXCR 4的肺癌细胞的可能性。将LFC 131肽缀合至羧甲基纤维素钠涂覆的聚（DL-乳酸-共乙醇酸）（PLGA）纳米颗粒。在称为A549细胞的腺癌人肺泡基底上皮细胞中，负载阿霉素的LFC 131缀合纳米颗粒（LFC 131-DOX NP）的结合和细胞摄取比非靶向纳米颗粒更高且更快。通过使用游离LFC 131肽或抗CXCR 4单克隆抗体证实CXCR 4介导的LFC 131-DOX NP内化的特异性。细胞研究表明，由PLGA纳米颗粒提供的阿霉素的持续释放可以使LFC 131-DOX NP成为靶向和控释药物递送系统。(C)2014爱思唯尔有限公司版权所有。
Doxorubicin is used to treat a variety of cancers, but dose limiting toxicity or intrinsic and acquired resistance limits its application in many types of cancer. CXCR4 is a chemokine receptor which implicates in metastasis of cancers including lung cancer. LFC131, a peptide inhibitor of CXCR4-ligand binding, is a linear type of low molecular weight CXCR4 antagonist. In this study, we investigated the possibility of using LFC131 conjugated nanoparticles for targeted delivering doxorubicin to CXCR4 expressing lung cancer cells. The LFC131 peptide was conjugated to sodium carboxylmethyl cellulose coated poly(DL-lactic-coglycolic acid) (PLGA) nanoparticles. Binding and cellular uptake of doxorubicin-loaded LFC131 conjugated nanoparticles (LFC131-DOX NP) in adenocarcinomic human alveolar basal epithelial cells called A549 cells were higher and faster than that of untargeted nanoparticles. The specificity of CXCR4-mediated internalization of LFC131-DOX NPs was confirmed by using free LFC131 peptide or anti-CXCR4 monoclonal antibody. Cell studies suggested that sustained release of doxorubicin afforded by PLGA nanoparticles may enable LFC131-DOX NP as a targeted and controlled release drug delivery system. (C) 2014 Elsevier B.V. All rights reserved.