Qu Ding, Liu Mingjian, Huang Mengmeng, Wang Lixiang, Chen Yan, Liu Congyan, Liu Yuping
Research Center for Multicomponent Traditional Medicine and Microecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine; Research Center for Multicomponent Traditional Medicine and Microecology, Jiangsu Provincial Academy of Traditional Chinese Medicine, Nanjing, People's Republic of China.
Research Center for Multicomponent Traditional Medicine and Microecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine.
Int J Nanomedicine. 2017 Mar 14;12:2045-2059. doi: 10.2147/IJN.S125293. eCollection 2017.
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.
一个结合了合理成分与肿瘤靶向性的纳米级药物递送平台对于增强抗癌治疗效果和减少副作用具有重要意义。在本研究中，我们开发了一种由薏苡仁成分自组装而成的辛酰半乳糖酯修饰微乳体系（Gal(oct)-C-MEs），其通过去唾液酸糖蛋白受体介导的内吞作用提高了肿瘤蓄积，并通过多成分介导的协同效应促进了抗肿瘤疗效。通过绿色酶促反应和多维表征合成了产率为82.3%的辛酰半乳糖酯（Gal(oct)）。呈球形的Gal(oct)-C-MEs具有小且均匀的粒径（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，内化的Gal(oct)-C-ME相对于基于薏苡仁成分的微乳（C-MEs）高出2.28倍。Gal(oct)-C-MEs对HepG2细胞的半数抑制浓度为46.5±2.4 μg/mL，显著高于C-MEs。重要的是，用Cy5/Gal(oct)-C-MEs处理的荷HepG2异种移植瘤裸鼠的肿瘤内荧光相对于用Cy5/C-MEs处理高出1.9倍。在体内抗肿瘤疗效研究中，胃内给予Gal(oct)-C-MEs 14天的荷HepG2异种移植瘤裸鼠在所有治疗中表现出最强的肿瘤生长抑制作用以及对肝脏和肾脏的最低毒性。总之，Gal(oct)-C-ME作为一种高效且安全的抗癌药物递送系统，在肝癌治疗中显示出有前景的潜力。
