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载姜黄素的智能介孔硅纳米粒子抑制肝癌。

Smart Mesoporous Silica Nanoparticles Loading Curcumin Inhibit Liver Cancer.

机构信息

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.

Department of Pharmacy, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China.

出版信息

J Agric Food Chem. 2024 Nov 20;72(46):25743-25754. doi: 10.1021/acs.jafc.4c08202. Epub 2024 Nov 7.

Abstract

Curcumin (CUR) as one of the natural edible pigments is approved by the World Health Organization due to its nontoxic and anticancer effect. However, the utility of CUR is restricted due to its low oral bioavailability. Nanoparticle drug delivery systems like mesoporous silica nanoparticles (MSNs) have been extensively used due to their high specific surface area, high loading rate, and ease of modification. This study developed lactobionic acid (LA)-modified carboxymethyl chitosan (CMCS)-coated MSNs to deliver CUR specifically targeting hepatocellular carcinoma. Among these nanoparticles, LA targets liver cancer cells. CMCS utilizes pH-responsive release of CUR. The LA-CMCS-MSN@CUR (MSN@CUR) were evaluated using several methods, including Fourier transform infrared spectroscopy, transmission electron microscopy, and zeta potential measurements. Liver cellular uptake of MSN@CUR depends on a specific LA receptor-mediated endocytosis mechanism. Additionally, MSN@CUR performed with a better antitumor effect than Cur in H22 orthotopic transplantation of liver cancer and H22 solid tumor mouse models. Treatment with MSN@CUR significantly reduced the protein of VEGF, p-PI3K, and AKT, increased the protein of caspases 3 and 8, ultimately inhibited tumor migration, and promoted apoptosis. This study provides a new path for delivery of natural active ingredients with excellent bioavailability in the antitumor field.

摘要

姜黄素(CUR)作为一种天然食用色素,因其无毒和抗癌作用而被世界卫生组织批准使用。然而,由于其口服生物利用度低,CUR 的应用受到限制。介孔硅纳米粒子(MSNs)等纳米药物递送系统由于具有高比表面积、高载药率和易于修饰等特点,得到了广泛的应用。本研究开发了乳酸(LA)修饰的羧甲基壳聚糖(CMCS)包覆的 MSNs,以特异性靶向肝癌递送 CUR。在这些纳米粒子中,LA 靶向肝癌细胞。CMCS 利用 CUR 的 pH 响应释放。采用傅里叶变换红外光谱、透射电子显微镜和zeta 电位测量等方法对 LA-CMCS-MSN@CUR(MSN@CUR)进行了评价。MSN@CUR 的肝细胞摄取取决于特定的 LA 受体介导的内吞作用机制。此外,MSN@CUR 在 H22 肝癌原位移植和 H22 实体瘤小鼠模型中的抗肿瘤效果优于 Cur。用 MSN@CUR 治疗可显著降低 VEGF、p-PI3K 和 AKT 蛋白的表达,增加 caspase 3 和 8 的蛋白表达,最终抑制肿瘤迁移,促进细胞凋亡。本研究为具有优异生物利用度的天然活性成分在抗肿瘤领域的递送提供了新的途径。

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