Department of Biomedical Engineering, National University of Singapore, 15 Kent Ridge Crescent, Singapore119276, Singapore.
NUS Environmental Research Institute (NERI), National University of Singapore, 5A Engineering Drive 1, Singapore117411, Singapore.
Biomacromolecules. 2022 Nov 14;23(11):4586-4596. doi: 10.1021/acs.biomac.2c00838. Epub 2022 Sep 14.
We report the synthesis and characterization of an amphiphilic polymer comprising a hydrophobic palmitoyl (Pal) group and a zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC) block, which is capable of forming micelles as a drug carrier system for delivering hydrophobic anticancer drugs such as doxorubicin (DOX). We hypothesize that the sharp polarity contrast between the Pal domain and the pMPC block would strengthen the micelles and improve the drug loading capacity, while the pMPC shells improve the micelle stability and cellular uptake efficiency. In this study, the Pal-pMPC polymer was characterized and compared with a Pal-poly(ethylene glycol) (Pal-PEG) polymer in terms of their micelle formation, cytotoxicity, and drug loading of DOX. The DOX-loaded Pal-pMPC micelles were further evaluated for the cellular uptake and anticancer activities in cell culture systems including the non-multidrug-resistance HeLa cell line and the multidrug-resistance AT3B-1 cell line. The results showed that the Pal-pMPC polymer had a minimal toxicity. The Pal-pMPC micelles exhibited higher drug loading capacity and enhanced cellular internalization efficiency compared to micelles formed by the Pal-PEG polymer. It was also found that DOX-loaded Pal-pMPC micelles exhibited a more efficient anticancer effect than Pal-PEG micelles in multidrug-resistance cancer cells in an environment with fetal bovine serum.
我们报告了一种两亲聚合物的合成与表征,该聚合物由疏水的棕榈酰(Pal)基团和两性离子聚(2-甲基丙烯酰氧基乙基磷酸胆碱)(pMPC)嵌段组成,可作为载药系统形成胶束,用于输送疏水性抗癌药物,如阿霉素(DOX)。我们假设 Pal 结构域和 pMPC 嵌段之间的强烈极性对比将增强胶束并提高载药能力,而 pMPC 壳则提高胶束的稳定性和细胞摄取效率。在这项研究中,我们对 Pal-pMPC 聚合物进行了表征,并将其与 Pal-聚乙二醇(Pal-PEG)聚合物进行了比较,评估了它们的胶束形成、细胞毒性和 DOX 的载药量。进一步评估了载有 DOX 的 Pal-pMPC 胶束在细胞培养系统中的细胞摄取和抗癌活性,包括非多药耐药的 HeLa 细胞系和多药耐药的 AT3B-1 细胞系。结果表明,Pal-pMPC 聚合物的毒性最小。与由 Pal-PEG 聚合物形成的胶束相比,Pal-pMPC 胶束具有更高的载药能力和增强的细胞内化效率。还发现,在含有胎牛血清的环境中,载有 DOX 的 Pal-pMPC 胶束在多药耐药癌细胞中的抗癌效果比 Pal-PEG 胶束更有效。
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