Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Grand Health Research Institute of Hefei Comprehensive National Science Center, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Anhui University of Chinese Medicine, Hefei 230012, China; Engineering Technology Research Center of Modernized Pharmaceutics, Anhui Education Department (AUCM), Hefei 230012, Anhui, China.
Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Grand Health Research Institute of Hefei Comprehensive National Science Center, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Anhui University of Chinese Medicine, Hefei 230012, China; Engineering Technology Research Center of Modernized Pharmaceutics, Anhui Education Department (AUCM), Hefei 230012, Anhui, China.
Eur J Pharm Biopharm. 2024 Oct;203:114454. doi: 10.1016/j.ejpb.2024.114454. Epub 2024 Aug 13.
In our previous studies, 3-O-β-D-galactosylated resveratrol (Gal-Res) was synthesized by structural modification and then 3-O-β-D-galactosylated resveratrol polydopamine nanoparticles (Gal-Res NPs) were successfully prepared to improve the bioavailability and liver distribution of Res. However, the pharmacodynamic efficacy and specific mechanism of Gal-Res NPs on hepatocellular carcinoma remain unclear. Herein, liver cancer model mice were successfully constructed by xenograft tumor modeling. Gal-Res NPs (34.2 mg/kg) significantly inhibited tumor growth of the liver cancer model mice with no significant effect on their body weight and no obvious toxic effect on major organs. Additionally, in vitro cellular uptake assay showed that Gal-Res NPs (37.5 μmol/L) increased the uptake of Gal-Res by Hepatocellular carcinoma (HepG2) cells, and significantly inhibited the cell migration and invasion. The experimental results of Hoechst 33342/propyl iodide (PI) double staining and flow cytometry both revealed that Gal-Res NPs could remarkably promote cell apoptosis. Moreover, the Western blot results revealed that Gal-Res NPs significantly regulated the Bcl-2/Bax and AKT/GSK3β/β-catenin signaling pathways. Taken together, the in vitro/in vivo results demonstrated that Gal-Res NPs significantly improved the antitumor efficiency of Gal-Res, which is a potential antitumor drug delivery system.
在我们之前的研究中，通过结构修饰合成了 3-O-β-D-半乳糖基白藜芦醇（Gal-Res），然后成功制备了 3-O-β-D-半乳糖基白藜芦醇聚多巴胺纳米粒（Gal-Res NPs），以提高 Res 的生物利用度和肝脏分布。然而，Gal-Res NPs 对肝细胞癌的药效学疗效和具体作用机制仍不清楚。在此，通过异种移植肿瘤建模成功构建了肝癌模型小鼠。Gal-Res NPs（34.2mg/kg）显著抑制肝癌模型小鼠的肿瘤生长，对其体重无明显影响，对主要器官也无明显毒性作用。此外，细胞摄取实验表明，Gal-Res NPs（37.5μmol/L）增加了肝癌细胞（HepG2）对 Gal-Res 的摄取，并显著抑制细胞迁移和侵袭。Hoechst 33342/碘化丙啶（PI）双重染色和流式细胞术的实验结果均表明，Gal-Res NPs 可显著促进细胞凋亡。此外，Western blot 结果表明，Gal-Res NPs 显著调节 Bcl-2/Bax 和 AKT/GSK3β/β-catenin 信号通路。综上所述，体内外实验结果表明，Gal-Res NPs 显著提高了 Gal-Res 的抗肿瘤效率，是一种有潜力的抗肿瘤药物递送系统。
