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使用分子对接方法和体外研究制备并表征负载MUC-30的聚合物胶束对MCF-7细胞系的作用

Preparation and Characterization of MUC-30-Loaded Polymeric Micelles against MCF-7 Cell Lines Using Molecular Docking Methods and In Vitro Study.

作者信息

Nasongkla Norased, Tuchinda Patoomratana, Munyoo Bamroong, Eawsakul Komgrit

机构信息

Department of Biomedical Engineering, Faculty of Engineering, Mahidol University, Nakhon Pathom 73170, Thailand.

Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Mahidol University, Nakhon Bangkok 10400, Thailand.

出版信息

Evid Based Complement Alternat Med. 2021 May 28;2021:5597681. doi: 10.1155/2021/5597681. eCollection 2021.

Abstract

MUC-30 is a hydrophobic compound which is active against the MCF-7 cancer cell line. In this study, MUC-30 was loaded in polymeric micelles to improve the water solubility and release rate. For prolonged MUC-30 release, MUC-30 was encapsulated in polymeric micelles using PEG--PLA and PEG--PCL as materials. Micelles prepared with 1 : 9 per ratios by film hydration achieved the highest entrapment efficiency (EE%). The EE% of MUC-30-loaded PEG--PCL micelles was approximately 30% greater than that of PEG--PLA micelles, due to the different H-bond formations between MUC-30 and the polymer membrane (PCL, 4; PLA, 3). The cytotoxic activity of MUC-30 against EGFR theoretically presented 399.31 nM (IC = 282.26 ng/mL) by molecular docking. In vitro cytotoxic activity of MUC-30 was confirmed by MTT assay. MUC-30 (IC = 11 ± 0.39 ng/mL) showed three-fold higher activity over MUC-30-loaded PEG--PLA micelles (IC = 37 ± 1.18 ng/mL) and two-fold higher over PEG--PCL micelles (IC = 75 ± 3.97 ng/mL). This was due to the higher release rate of MUC-30 from PEG--PLA micelles compared to PEG--PCL micelles. Therefore, MUC-30-loaded PEG--PLA micelles could be a promising candidate for breast cancer chemotherapy.

摘要

MUC - 30是一种对MCF - 7癌细胞系具有活性的疏水化合物。在本研究中,MUC - 30被载入聚合物胶束以提高其水溶性和释放速率。为了实现MUC - 30的长效释放,以聚乙二醇 - 聚乳酸(PEG - PLA)和聚乙二醇 - 聚己内酯(PEG - PCL)为材料将MUC - 30封装在聚合物胶束中。通过薄膜水化法以1∶9的比例制备的胶束具有最高的包封率(EE%)。载入MUC - 30的PEG - PCL胶束的EE%比PEG - PLA胶束大约高30%,这是由于MUC - 30与聚合物膜(PCL为4,PLA为3)之间形成的氢键不同。通过分子对接理论上显示MUC - 30对表皮生长因子受体(EGFR)的细胞毒性活性为399.31 nM(IC = 282.26 ng/mL)。通过MTT法证实了MUC - 30的体外细胞毒性活性。MUC - 30(IC = 11±0.39 ng/mL)的活性比载入MUC - 30的PEG - PLA胶束(IC = 37±1.18 ng/mL)高两倍,比PEG - PCL胶束(IC = 75±3.97 ng/mL)高1倍。这是因为与PEG - PCL胶束相比,MUC - 30从PEG - PLA胶束中的释放速率更高。因此,载入MUC - 30的PEG - PLA胶束可能是乳腺癌化疗的一个有前景的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f7/8179782/704f68afd03b/ECAM2021-5597681.001.jpg

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