Lin Yun Hsuan, Chen Ching-Yi
Department of Chemical Engineering, College of Engineering, National Chung Cheng University, Chia-Yi County 621301, Taiwan.
Polymers (Basel). 2020 Oct 4;12(10):2280. doi: 10.3390/polym12102280.
Curcumin (CUR) is a natural phenolic product used as a high-efficiency and low-toxicity anticancer drug and photosensitizer. However, it has a poor aqueous solubility and a lack of target specificity, which limits its clinical applications. Hence, we developed a folate-conjugated polymeric micelle to enhance the efficient delivery of CUR for effective cancer cell targeting and anticancer efficiency. A series of biocompatible folate-conjugated poly(2-(methacryloyloxy)ethylphosphoryl- choline)--poly(ε-caprolactone) (FPM) was synthesized with different hydrophobic lengths and folate contents. The prepared CUR-loaded micelles (CUR-FPM) possessed several superior properties, including an excellent drug loading capacity (6.3 ± 1.2%), improved CUR aqueous stability, fast-sustained CUR release in an acidic environment, and efficient intracellular production of reactive oxygen species. The in vitro cytotoxicity demonstrated that the CUR-FPM micelles efficiently suppressed the growth of HeLa cells (folate-receptor overexpression) compared to that of HT-29 cells, and a competition study showed less cytotoxic effect when free folic acid blocked the folate receptor, indicating the folate conjugation played the role of targeting the specific cells well. Moreover, the CUR-mediated photodynamic therapy (PDT) by CUR-FPM micelles under irradiation further inhibited the proliferation of cancer cells. All these results indicate that the CUR-FPM micelles could be a promising delivery system for folate-overexpressing cancer cells, complementary chemotherapy, and CUR-mediated photodynamic therapy.
姜黄素（CUR）是一种天然酚类产物，用作高效低毒的抗癌药物和光敏剂。然而，它的水溶性差且缺乏靶向特异性，这限制了其临床应用。因此，我们开发了一种叶酸共轭聚合物胶束，以增强CUR的有效递送，实现对癌细胞的有效靶向和抗癌效率。合成了一系列具有不同疏水长度和叶酸含量的生物相容性叶酸共轭聚（2-（甲基丙烯酰氧基）乙基磷酰胆碱）-聚（ε-己内酯）（FPM）。制备的载CUR胶束（CUR-FPM）具有多种优异性能，包括出色的载药能力（6.3±1.2%）、改善的CUR水稳定性、在酸性环境中快速持续的CUR释放以及细胞内活性氧的高效产生。体外细胞毒性表明，与HT-29细胞相比，CUR-FPM胶束能有效抑制HeLa细胞（叶酸受体过表达）的生长，一项竞争研究表明，当游离叶酸阻断叶酸受体时，细胞毒性作用较小，这表明叶酸共轭起到了很好的靶向特定细胞的作用。此外，CUR-FPM胶束在光照下介导的CUR光动力疗法（PDT）进一步抑制了癌细胞的增殖。所有这些结果表明，CUR-FPM胶束可能是一种有前途的用于叶酸过表达癌细胞的递送系统、辅助化疗和CUR介导的光动力疗法。
