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基于姜黄素包裹融合蛋白的纳米载体展现出对表皮生长因子受体靶向治疗结直肠癌的高效性。

Curcumin-Encapsulated Fusion Protein-Based Nanocarrier Demonstrated Highly Efficient Epidermal Growth Factor Receptor-Targeted Treatment of Colorectal Cancer.

作者信息

Han Zhiqiang, Song Bo, Yang Jiyuan, Wang Bo, Ma Zhongqiang, Yu Long, Li Yuanhao, Xu Haijin, Qiao Mingqiang

机构信息

The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, P.R. China.

Remegen Co., Ltd., Shandong 264000, P.R. China.

出版信息

J Agric Food Chem. 2022 Dec 14;70(49):15464-15473. doi: 10.1021/acs.jafc.2c04668. Epub 2022 Dec 1.

Abstract

Curcumin, a polyphenol derived from turmeric, has multiple biological functions, such as anti-inflammatory, antioxidant, antibacterial and, above all, antitumor activity. Colorectal cancer is a common malignancy of the gastrointestinal tract with an extremely high mortality rate. However, the low bioavailability and poor targeting properties of curcumin generally limit its clinical application. In the present study, we designed a fusion protein GE11-HGFI as a nanodrug delivery system. The protein was connected by flexible linkers, inheriting the self-assembly properties of hydrophobin HGFI and the targeting ability of GE11. The data show that the encapsulation of curcumin by fusion protein GE11-HGFI can form uniform and stable nanoparticles with a size of only 80 nm. In addition, the nanocarrier had high encapsulation efficiency for curcumin and made it to release sustainably. Notably, the drug-loaded nanosystem selectively targeted colorectal cancer cells with high epidermal growth factor receptor expression, resulting in high aggregated concentrations of curcumin at tumor sites, thus showing a significant anticancer effect. These results suggest that the nanocarrier fusion protein has the potential to be a novel strategy for enhancing molecular bioactivity and drug targeting in cancer therapy.

摘要

姜黄素是一种从姜黄中提取的多酚,具有多种生物学功能,如抗炎、抗氧化、抗菌,最重要的是具有抗肿瘤活性。结直肠癌是胃肠道常见的恶性肿瘤,死亡率极高。然而,姜黄素的低生物利用度和较差的靶向性通常限制了其临床应用。在本研究中,我们设计了一种融合蛋白GE11-HGFI作为纳米药物递送系统。该蛋白通过柔性接头连接,继承了疏水蛋白HGFI的自组装特性和GE11的靶向能力。数据表明,融合蛋白GE11-HGFI对姜黄素的包封可形成尺寸仅为80 nm的均匀稳定纳米颗粒。此外,该纳米载体对姜黄素具有高包封效率,并使其可持续释放。值得注意的是,载药纳米系统选择性地靶向表皮生长因子受体高表达的结直肠癌细胞,导致姜黄素在肿瘤部位高度聚集,从而显示出显著的抗癌效果。这些结果表明,纳米载体融合蛋白有可能成为癌症治疗中增强分子生物活性和药物靶向性的新策略。

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