Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, College of Polymer Science and Engineering, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China; Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB3 0AS, UK.
Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, College of Polymer Science and Engineering, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
J Control Release. 2019 Oct;311-312:104-116. doi: 10.1016/j.jconrel.2019.08.037. Epub 2019 Sep 1.
Currently, most anti-cancer therapies are still haunted by serious and deleterious adverse effects. Here, we report a highly biocompatible tumor cell-targeting delivery systems utilizing exosome-like vesicles (ELVs) that delivers a low-toxicity anti-cancer agent imperialine against non-small cell lung cancer (NSCLC). First, we introduced a novel micelle-aided method to efficiently load imperialine into intact ELVs. Then, integrin α3β1-binding octapeptide cNGQGEQc was modified onto ELV platform for tumor targeting as integrin α3β1 is overexpressed on NSCLC cells. This system not only significantly improved imperialine tumor accumulation and retention, but also had extremely low systemic toxicity both in vitro and in vivo. Our discoveries offer new ways to utilize ELV more efficiently for both drug loading and targeting. The solid pharmacokinetics improvement and extraordinary safety of this system also highlight possibilities of alternative long course cancer therapies using similar strategies.
目前，大多数抗癌疗法仍然受到严重且有害的不良反应的困扰。在这里，我们报告了一种利用外泌体样囊泡（ELV）的高度生物相容性肿瘤细胞靶向递药系统，该系统可递送低毒性抗癌药物千金藤素来治疗非小细胞肺癌（NSCLC）。首先，我们引入了一种新型胶束辅助方法，可有效地将千金藤素装载到完整的 ELV 中。然后，将整合素 α3β1 结合八肽 cNGQGEQc 修饰到 ELV 平台上以实现肿瘤靶向，因为整合素 α3β1 在 NSCLC 细胞中过表达。该系统不仅显著提高了千金藤素在肿瘤中的积累和保留，而且在体外和体内均具有极低的全身毒性。我们的发现为利用 ELV 更有效地进行药物负载和靶向提供了新途径。该系统的固体制剂药代动力学的显著改善和卓越的安全性也突出了使用类似策略进行替代长期癌症治疗的可能性。
