Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran; Department of Pharmaceutical Engineering, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran.
Department of Pharmaceutical Engineering, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran.
Bioorg Med Chem Lett. 2021 May 15;40:127907. doi: 10.1016/j.bmcl.2021.127907. Epub 2021 Mar 6.
Despite numerous beneficial therapeutic effects namely antioxidant and anti-inflammatory activity, Vitamin E has limited clinical applications due to its low water solubility. Throughout the present work, α-tocopherol's new PEGylated derivatives alongside with polyethylene glycol 300 (α-TPGT), 400 (α-TPGT), and 1000 (α-TPGT) were synthesized. A 1,2,3-triazole ring was utilized as a linker for the attachment of alpha tocopherol to the PEGs through a click reaction. The purified derivatives were characterized by the means of H NMR, C NMR, mass spectroscopy, UV-vis and FT-IR methods. Synthesized derivatives' capacity to produce self-assembly nanoparticles was evaluated employing the critical micelle concentration (CMC) values. The stability of the micelles was studied by size analysis. In vitro cytotoxicity of the products was investigated using MTT assay against MCF-7 breast cancer cells. The IC value for TPGT after 24 h treatment was 15.0 ± 1.8 µM, whereas no significant cytotoxicity effect was observed following the treatment of MCF-7 cells by TPGT. The present study showed that polymeric micelle TPGT possessed better physicochemical and biological properties including relatively lower CMC value, higher stability in FBS environment in addition to higher cytotoxicity against MCF-7 breast cancer cells compared to the lower molecular weight PEGylated derivatives. These results confirmed that increasing PEG chain length left a positive effect on the polymeric micelle properties and also improved the cytotoxicity effect of new PEGylated vitamin E derivatives.
尽管维生素 E 具有抗氧化和抗炎等诸多有益的治疗作用，但由于其水溶性低，其临床应用受到限制。在本工作中，我们合成了α-生育酚的新 PEG 衍生物以及聚乙二醇 300（α-TPGT）、400（α-TPGT）和 1000（α-TPGT）。通过点击反应，利用 1,2,3-三唑环作为连接物将α-生育酚连接到 PEG 上。通过 1 H NMR、13 C NMR、质谱、紫外可见分光光度法和傅里叶变换红外光谱法对纯化的衍生物进行了表征。采用临界胶束浓度（CMC）值评估了合成衍生物自组装纳米粒子的能力。通过粒径分析研究了胶束的稳定性。通过 MTT 法测定了产物对 MCF-7 乳腺癌细胞的体外细胞毒性。在 24 h 处理后，TPGT 的 IC 值为 15.0 ± 1.8 µM，而用 TPGT 处理 MCF-7 细胞后没有观察到明显的细胞毒性作用。本研究表明，与低分子量 PEG 化衍生物相比，聚合物胶束 TPGT 具有更好的物理化学和生物学特性，包括相对较低的 CMC 值、在 FBS 环境中的更高稳定性以及对 MCF-7 乳腺癌细胞更高的细胞毒性。这些结果证实，增加 PEG 链长对聚合物胶束性质有积极影响，并提高了新型 PEG 化维生素 E 衍生物的细胞毒性作用。
