Targeting tumor highly-expressed LAT1 transporter with amino acid-modified nanoparticles: Toward a novel active targeting strategy in breast cancer therapy
Targeting tumor highly-expressed LAT1 transporter with amino acid-modified nanoparticles: Toward a novel active targeting strategy in breast cancer therapy
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用氨基酸修饰的纳米颗粒靶向肿瘤高表达的 LAT1 转运蛋白：乳腺癌治疗中的新型主动靶向策略
DOI：
10.1016/j.nano.2016.11.012
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发表时间：
2017-04-01
影响因子：
5.4
通讯作者：
He, Zhonggui
中科院分区：
文献类型：
--
作者：
Li, Lin;Di, Xingsheng;He, Zhonggui
设计具有增加化疗药物细胞积累的主动靶向纳米载体是癌症治疗中一种有前途的策略。在此，我们报告了一种基于在多种癌症中过表达的大氨基酸转运蛋白 1 (LAT1) 的新型主动靶向策略。将谷氨酸与聚氧乙烯硬脂酸酯缀合作为靶向配体，以获得靶向 LAT1 的 PLGA 纳米颗粒。在 HeLa 和 MCF-7 细胞中研究了纳米粒子的靶向效率。与未修饰的纳米颗粒相比，LAT1 靶向纳米颗粒的细胞摄取和细胞毒性显着增加。更有趣的是，内化的LAT1与靶向纳米颗粒一起可以在3小时内循环回细胞膜，保证细胞膜上有足够的转运蛋白以供细胞连续摄取。 LAT1靶向纳米颗粒表现出更好的肿瘤聚集和抗肿瘤效果。这些结果表明，癌细胞上过表达的 LAT1 具有成为合理设计主动靶向纳米系统的高效靶标的巨大潜力。 (C) 2016 Elsevier Inc. 保留所有权利。
Designing active targeting nanocarriers with increased cellular accumulation of chemotherapeutic agents is a promising strategy in cancer therapy. Herein, we report a novel active targeting strategy based on the large amino acid transporter 1 (LAT1) overexpressed in a variety of cancers. Glutamate was conjugated to polyoxyethylene stearate as a targeting ligand to achieve LAT1-targeting PLGA nanoparticles. The targeting efficiency of nanoparticles was investigated in HeLa and MCF-7 cells. Significant increase in cellular uptake and cytotoxicity was observed in LAT1-targeting nanoparticles compared to the unmodified ones. More interestingly, the internalized LAT1 together with targeting nanoparticles could recycle back to the cell membrane within 3 h, guaranteeing sufficient transporters on cell membrane for continuous cellular uptake. The LAT1 targeting nanoparticles exhibited better tumor accumulation and antitumor effects. These results suggested that the overexpressed LAT1 on cancer cells holds a great potential to be a high-efficiency target for the rational design of activetargeting nanosystems. (C) 2016 Elsevier Inc. All rights reserved.