Jiang Linhai, Cai Xiaoliang, Li Sheng, Miao Ying, Yang Xiaoyu, Lin Manbian, Chen Liang, He Xiaozheng, Weng Zuquan
Fuzhou Traditional Chinese Medicine Hospital, Fuzhou, China.
College of Biological Science and Engineering, Fuzhou University, Fuzhou, China.
Front Pharmacol. 2021 Nov 3;12:755054. doi: 10.3389/fphar.2021.755054. eCollection 2021.
It is well documented that curcumin (CUR), as a polyphenol molecule originated from turmeric, has many advantages such as antioxidative, anti-inflammatory, neuroprotective, and antitumor effects. However, because of its poor water solubility and low bioavailability, the biomedical applications of CUR are limited. So, in this study, we modified CUR with conjugation to a food-derived hydrophilic hydroxyethyl starch (HES) an ester linkage to fabricate the amphiphilic conjugate HES-CUR prior to self-assembling into uniform nanoparticles (HES-CUR NPs). And, the results of the H NMR spectra and FT-IR spectrum showed successful synthesis of HES-CUR NPs; moreover, the solubility and the drug loading efficiency of CUR were significantly increased. Next, we further explored the differences on the antitumor effects between HES-CUR NPs and CUR in HepG2 cells, and the results of the CCK8-assay and cell counting experiment showed that HES-CUR NPs exhibited a more significant antiproliferative effect than that of CUR in HepG2 cells. And HepG2 cells were more sensitive to apoptosis induced by HES-CUR NPs as evidenced by flow cytometry, increased cytochrome c level, and decreased full length caspase-3 and Bcl-2 protein expressions. Additionally, we found that the efficacy of HES-CUR NPs against HepG2 cells might be related to the enhanced degree of mitochondrial damage (decrease of the mitochondrial membrane potential and ATP) and autophagy (increased levels of Beclin-1 and LC3-II proteins). So, the findings in this study suggest that HES-CUR NPs have a great application potential in antitumor efficacy and play an important role in multiple signal pathways.
有充分文献记载，姜黄素（CUR）作为一种源自姜黄的多酚分子，具有许多优点，如抗氧化、抗炎、神经保护和抗肿瘤作用。然而，由于其水溶性差和生物利用度低，CUR的生物医学应用受到限制。因此，在本研究中，我们通过与食品来源的亲水性羟乙基淀粉（HES）共轭（酯键连接）对CUR进行修饰，在自组装成均匀纳米颗粒（HES-CUR NPs）之前制备两亲性共轭物HES-CUR。并且，¹H NMR光谱和FT-IR光谱结果表明成功合成了HES-CUR NPs；此外，CUR的溶解度和载药效率显著提高。接下来，我们进一步探究了HES-CUR NPs和CUR在HepG2细胞中抗肿瘤作用的差异，CCK8检测和细胞计数实验结果表明，HES-CUR NPs在HepG2细胞中表现出比CUR更显著的抗增殖作用。流式细胞术、细胞色素c水平升高以及全长caspase-3和Bcl-2蛋白表达降低表明，HepG2细胞对HES-CUR NPs诱导的凋亡更敏感。此外，我们发现HES-CUR NPs对HepG2细胞的疗效可能与线粒体损伤（线粒体膜电位和ATP降低）和自噬（Beclin-1和LC3-II蛋白水平升高）的增强程度有关。因此，本研究结果表明，HES-CUR NPs在抗肿瘤疗效方面具有巨大的应用潜力，并在多个信号通路中发挥重要作用。
