Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
Toxicol Appl Pharmacol. 2023 May 1;466:116470. doi: 10.1016/j.taap.2023.116470. Epub 2023 Mar 17.
Currently, liposomes have emerged as efficient and safer nano-carriers for targeted therapy in different cancers. This work aimed to employ PEGylated liposomal doxorubicin (Doxil®/PLD), modified with AR13 peptide, to target Muc1 on the surface of colon cancerous cells. We performed molecular docking and simulation studies (using Gromacs package) of AR13 peptide against Muc1 to analyze and visualize the peptide-Muc1 binding combination. For in vitro analysis, the AR13 peptide was post-inserted into Doxil® and verified by TLC, H NMR, and HPLC techniques. The zeta potential, TEM, release, cell uptake, competition assay, and cytotoxicity studies were performed. In vivo antitumor activities and survival analysis on mice bearing C26 colon carcinoma were studied. Results showed that after 100 ns simulation, a stable complex between AR13 and Muc1 formed, and molecular dynamics analysis confirmed this interaction. In vitro analysis demonstrated significant enhancement of cellular binding and cell uptake. The results of in vivo study on BALB/c mice bearing C26 colon carcinoma, revealed an extended survival time to 44 days and higher tumor growth inhibition compared to Doxil®. Thus, the AR13 peptide could be explored as a potent ligand for Muc1, improving therapeutic antitumor efficiency in colon cancer cells.
目前，脂质体已成为针对不同癌症的靶向治疗的高效且更安全的纳米载体。本工作旨在利用聚乙二醇化阿霉素脂质体（Doxil®/PLD），通过 AR13 肽进行修饰，以针对结肠癌细胞表面的 Muc1 进行靶向治疗。我们对 AR13 肽与 Muc1 进行了分子对接和模拟研究（使用 Gromacs 软件包），以分析和可视化肽-Muc1 结合组合。为了进行体外分析，将 AR13 肽插入 Doxil®中，并通过 TLC、H NMR 和 HPLC 技术进行验证。进行了 zeta 电位、TEM、释放、细胞摄取、竞争实验和细胞毒性研究。研究了携带 C26 结肠癌细胞的小鼠的体内抗肿瘤活性和生存分析。结果表明，在 100ns 模拟后，AR13 与 Muc1 之间形成了稳定的复合物，分子动力学分析证实了这种相互作用。体外分析表明细胞结合和细胞摄取显著增强。在携带 C26 结肠癌细胞的 BALB/c 小鼠体内研究的结果表明，与 Doxil®相比，生存时间延长至 44 天，肿瘤生长抑制率更高。因此，AR13 肽可以作为 Muc1 的有效配体进行探索，提高结肠癌细胞的治疗抗肿瘤效率。
