Department of Radiology, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, Shandong, China.
Front Immunol. 2024 Nov 14;15:1500998. doi: 10.3389/fimmu.2024.1500998. eCollection 2024.
Resveratrol (Res), a Chinese herbal extract, has demonstrated a remarkable and distinct antitumor effect, characterized by prolonged efficacy and minimal adverse reactions. However, the bioavailability of Res in animals is hindered by limited absorption rates. Therefore, it is crucial to enhance the tumor-targeting ability of resveratrol to optimize cancer treatment outcomes by improving its bioavailability. Herein, we attempt to employ a functionalized nanoparticle drug carrier system based on polyamine-amine (PAMAM) dendrimers for targeted delivery of resveratrol in hepatocellular carcinoma cancer treatment. Initially, galactose-modified fifth-generation (G5) PAMAM dendrimers (G5-Gal) were synthesized through coupling reactions, followed by the synthesis of glycosylated dendrimers incorporating resveratrol (G5(Res)-Gal) physical encapsulation. The G5-Gal or G5(Res)-Gal complexes were characterized using H NMR spectroscopy, zeta and size analysis, and UV spectrophotometry. Additionally, Hepa1-6 mouse hepatoma cells were utilized as model cells to assess the targeting capability of G5-Gal toward hepatoma cells using flow cytometry. Finally, CCK-8 assay was employed to evaluate the impact of G5(Res)-Gal on normal liver cells as well as its cytotoxicity against different types of hepatoma cells. Furthermore, cell apoptosis experiments were conducted to further evaluate the effects of G5(Res)-Gal on Hepa1-6 cells. The aim of this project is to establish a solid theoretical framework and provide technical expertise to optimize the application of resveratrol and advance its delivery system.
白藜芦醇(Res)是一种中草药提取物,具有显著而独特的抗肿瘤作用,其疗效持久,不良反应极小。然而,Res 在动物体内的生物利用度受到吸收速率有限的限制。因此,通过提高其生物利用度来增强 Res 的肿瘤靶向能力,对于优化癌症治疗效果至关重要。在此,我们尝试采用基于聚胺-胺(PAMAM)树枝状大分子的功能化纳米药物载体系统,实现对肝癌的靶向给药。首先,通过偶联反应合成了半乳糖修饰的第五代(G5)PAMAM 树枝状大分子(G5-Gal),然后合成了含有白藜芦醇的糖基化树枝状大分子(G5(Res)-Gal)物理包封物。使用 H NMR 光谱、Zeta 和大小分析以及紫外分光光度法对 G5-Gal 或 G5(Res)-Gal 复合物进行了表征。此外,还使用 Hepa1-6 小鼠肝癌细胞作为模型细胞,通过流式细胞术评估 G5-Gal 对肝癌细胞的靶向能力。最后,使用 CCK-8 assay 评估 G5(Res)-Gal 对正常肝细胞的影响及其对不同类型肝癌细胞的细胞毒性。此外,还进行了细胞凋亡实验,以进一步评估 G5(Res)-Gal 对 Hepa1-6 细胞的影响。本项目的目的是建立一个坚实的理论框架,并提供技术专长,以优化白藜芦醇的应用并推进其递药系统。