Octanoyl galactose ester-modified microemulsion system self-assembled by coix seed components to enhance tumor targeting and hepatoma therapy.
Octanoyl galactose ester-modified microemulsion system self-assembled by coix seed components to enhance tumor targeting and hepatoma therapy.
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薏苡仁成分自组装辛酰半乳糖酯修饰微乳系统增强肿瘤靶向和肝癌治疗
DOI：
10.2147/ijn.s125293
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发表时间：
2017
影响因子：
8
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Qu D;Liu M;Huang M;Wang L;Chen Y;Liu C;Liu Y
合理的成分组合和肿瘤靶向性的纳米给药平台对于增强抗肿瘤治疗效果和降低毒副作用具有重要意义。本研究以薏苡仁为主要成分，通过Gal（oct）-C-MEs自组装形成辛酰半乳糖酯修饰的微乳体系，通过去唾液酸糖蛋白受体介导的内吞作用改善肿瘤蓄积，并通过多组分协同作用提高抗肿瘤疗效。采用绿色酶促反应合成了辛酰半乳糖酯（Gal（oct）），并对其进行了多维表征，收率为82.3%。球形的Gal（oct）-C-ME具有小而均匀的粒径（58.49±1.03 nm）、窄的多分散指数（0.09±0.01）和中性表面电荷（−5.82±0.57 mV）。在细胞摄取研究中，相对于基于薏苡仁组分的微乳液（C-ME），内化的Gal（oct）-C-ME高2.28倍。Gal（oct）-C-MEs对HepG 2细胞的半数抑制浓度为46.5±2.4 μg/mL，明显高于C-MEs。重要的是，用Cy 5/Gal（oct）-C-ME处理的携带HepG 2异种移植物的裸鼠的肿瘤内荧光相对于用Cy 5/C-ME处理高1.9倍。在体内抗肿瘤功效的研究中，在所有治疗中，胃内给予Gal（oct）-C-ME 14天的荷HepG 2异种移植物的裸鼠表现出对肿瘤生长的最强抑制和对肝脏和肾脏的最低毒性。Gal（oct）-C-ME作为一种高效、安全的抗肿瘤给药系统，在肝癌治疗中显示出良好的应用前景。
A nanosized drug delivery platform with a combination of rational components and tumor targeting is significant for enhancement of anticancer therapy and reduction of side effects. In this study, we developed a octanoyl galactose ester-modified microemulsion system self-assembled by coix seed components (Gal(oct)-C-MEs), which improved the tumor accumulation through asialoglycoprotein receptor-mediated endocytosis and promoted the antitumor efficacy through multicomponent-mediated synergistic effect. Octanoyl galactose ester (Gal(oct)) with a yield of 82.3% was synthesized through a green enzymatic reaction and multidimensional characterization. Gal(oct)-C-MEs with a spherical shape had a small and uniform particle size (58.49±1.03 nm), narrow polydispersity index (0.09±0.01) and neutral surface charge (−5.82±0.57 mV). In the cellular uptake studies, the internalized Gal(oct)-C-ME was 2.28-fold higher relative to that of coix seed component-based microemulsions (C-MEs). The half-maximal inhibitory concentration of Gal(oct)-C-MEs against HepG2 cells was 46.5±2.4 μg/mL, which was notably higher than that of C-MEs. Importantly, the intratumor fluorescence of HepG2 xenograft-bearing nude mice treated with Cy5/Gal(oct)-C-MEs was 1.9-fold higher relative to treatment with Cy5/C-MEs. In the study of antitumor efficacy in vivo, HepG2 xenograft-bearing nude mice intragastrically administered Gal(oct)-C-MEs for 14 days exhibited the strongest inhibition of tumor growth and the lowest toxicity against liver and kidney among all the treatments. In summary, Gal(oct)-C-ME, as a highly effective and safe anticancer drug delivery system, showed promising potential for hepatoma therapy.