a School of Pharmacy , Liaoning University of Traditional Chinese Medicine , Dalian , China.
b Linyi Food and Drug Testing Center , Linyi , China.
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):1947-1960. doi: 10.1080/21691401.2019.1615932.
Presently, there are no few anticancer drugs that have been used clinically due to their poor targeting ability, short half-life period, non-selective distributions, generation of vasculogenic mimicry (VM) channels, high metastasis, and high recurrence rate. This study aimed to explore the effects of R modified epirubicin-dihydroartemisinin liposomes that could target non-small-cell lung cancer (NSCLC) cells, destroy VM channels, inhibit tumor metastasis, and explain the possible underlying mechanism. In vitro assays indicated that R modified epirubicin-dihydroartemisinin liposomes with ideal physicochemical characteristics could exhibit not only powerful cytotoxicity on A549 cells, but also the effective suppression of VM channels and tumor metastasis. Mechanistic studies manifested that R modified epirubicin-dihydroartemisinin liposomes could down-regulate the levels of VE-Cad, TGF-β1, MMP-2, and HIF-1α. In vivo assays indicated that R modified epirubicin-dihydroartemisinin liposomes could both increase the selective accumulation of chemotherapeutic drugs at tumor sites and show a targeting conspicuous of antitumor efficacy. In conclusion, the R modified epirubicin-dihydroartemisinin liposomes prepared in this study provide a treatment strategy with high efficiency for NSCLC.
目前，由于抗癌药物靶向能力差、半衰期短、分布非选择性、血管生成拟态（VM）通道的产生、高转移和高复发率，临床上已经有不少抗癌药物被使用。本研究旨在探索能够靶向非小细胞肺癌（NSCLC）细胞、破坏 VM 通道、抑制肿瘤转移的 R 修饰表阿霉素-青蒿琥酯脂质体的作用，并解释其可能的潜在机制。体外实验表明，具有理想理化特性的 R 修饰表阿霉素-青蒿琥酯脂质体不仅对 A549 细胞具有强大的细胞毒性，而且能有效抑制 VM 通道和肿瘤转移。机制研究表明，R 修饰表阿霉素-青蒿琥酯脂质体可以下调 VE-Cad、TGF-β1、MMP-2 和 HIF-1α 的水平。体内实验表明，R 修饰表阿霉素-青蒿琥酯脂质体既能增加化疗药物在肿瘤部位的选择性积累，又能表现出明显的靶向抗肿瘤疗效。总之，本研究制备的 R 修饰表阿霉素-青蒿琥酯脂质体为 NSCLC 提供了一种高效的治疗策略。
