Division of Bioengineering, School of Life Sciences and Bioengineering , Incheon National University , Incheon , Korea 22012.
Biomacromolecules. 2018 Aug 13;19(8):3257-3267. doi: 10.1021/acs.biomac.8b00543. Epub 2018 Jul 19.
Development of folate (FA)-functionalized gold nanoparticles (AuNPs) has greatly increased in recent years due to their potential in cancer treatment. As surface functionalization of polymer-free AuNPs with thiol groups could result in agglomeration and precipitation, AuNPs should be stabilized with an efficient polymer. In this study, citric acid-PEG branched polymer (CPEG) acted as a reducing as well as stabilizing agent in the synthesis of AuNPs. The thiol group of thioglycolic acid (TGA) attached to CPEG-stabilized AuNPs and interacted with the free carboxylic acid group on the surface of TGA-AuNP nanoconjugates. Stable TGA-AuNP nanoconjugates were obtained only with CPEG-stabilized AuNPs and not with citrate-stabilized AuNPs. The carboxylic acid group on the surface of AuNPs was used to attach FA via an EDC/NHS coupling reaction to obtain FA-TGA-AuNP nanoconjugates. In vitro cytotoxicity studies indicated that FA-TGA-AuNPs were not toxic to normal cells up to a concentration of 200 μg/mL. However, FA-TGA-AuNP nanoconjugates effectively inhibited proliferation of MCF-7 cancer cells at a low concentration of 25 μg/mL after 3 days of incubation. The anticancer activity of FA-TGA-AuNPs was enhanced by incorporating the anticancer drug 5-fluorouracil into the nanoconjugates, which exhibited sustained drug release up to 5 days. Hence, the developed biocompatible FA-TGA-AuNPs could be used for specific killing of breast cancer cells.
近年来，叶酸（FA）功能化金纳米粒子（AuNPs）的发展迅速增加，因为它们在癌症治疗方面具有潜力。由于聚合物自由的 AuNPs 用巯基进行表面功能化可能导致聚集和沉淀，因此 AuNPs 应该用有效的聚合物稳定。在这项研究中，柠檬酸-PEG 支化聚合物（CPEG）在 AuNPs 的合成中既作为还原剂又作为稳定剂。巯基乙醇酸（TGA）的巯基与 CPEG 稳定的 AuNPs 相连，并与 TGA-AuNP 纳米复合物表面上的游离羧酸基相互作用。只有用 CPEG 稳定的 AuNPs 才能获得稳定的 TGA-AuNP 纳米复合物，而用柠檬酸盐稳定的 AuNPs 则不行。AuNPs 表面上的羧酸基通过 EDC/NHS 偶联反应与 FA 相连，得到 FA-TGA-AuNP 纳米复合物。体外细胞毒性研究表明，FA-TGA-AuNPs 在浓度高达 200 μg/mL 时对正常细胞没有毒性。然而，FA-TGA-AuNP 纳米复合物在孵育 3 天后，在低浓度 25 μg/mL 时能有效抑制 MCF-7 癌细胞的增殖。将抗癌药物 5-氟尿嘧啶纳入纳米复合物中增强了 FA-TGA-AuNP 的抗癌活性，其药物释放可持续至 5 天。因此，开发的生物相容性 FA-TGA-AuNPs 可用于特异性杀伤乳腺癌细胞。
