pH-Sensitive mesoporous silica nanoparticles anticancer prodrugs for sustained release of ursolic acid and the enhanced anti-cancer efficacy for hepatocellular carcinoma cancer
pH-Sensitive mesoporous silica nanoparticles anticancer prodrugs for sustained release of ursolic acid and the enhanced anti-cancer efficacy for hepatocellular carcinoma cancer
复制标题
pH敏感介孔二氧化硅纳米颗粒抗癌前药，可持续释放熊果酸并增强对肝癌的抗癌功效
DOI：
10.1016/j.ejps.2016.10.019
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发表时间：
2017-01-01
影响因子：
4.6
通讯作者：
Shao, Jingwei
中科院分区：
文献类型：
--
作者：
Li, Tao;Chen, Xiufen;Shao, Jingwei
熊果酸（UA）作为一种天然产物，具有良好的抗癌活性、低毒性和良好的保肝功能。但其溶解度低、生物利用度差限制了其进一步的临床应用。为了克服这个问题，成功设计并合成了一种pH敏感的前药递送系统（UA@MSN-UA），该系统在药物和二氧化硅基介孔纳米球（MSN）之间结合了酸敏感的连接。研究了 UA@MSN-UA 纳米粒子的形状、粒径、zeta 电位、氮气吸附-脱附和红外 (IR) 光谱等物理化学性质。进一步评估了纳米颗粒的体外细胞毒性，包括增殖抑制、细胞周期分布和对人肝细胞癌 HepG2 细胞的凋亡作用。 TEM图像显示合成的MSN纳米粒子的尺寸接近球形，直径接近100 nm。体外细胞毒性测试表明，UA@MSN-UA纳米颗粒前药具有较高的增殖抑制作用，细胞周期阻滞在G2/M期，并显着引起HepG2细胞的早期和晚期凋亡，这有助于UA的高负载能力、高细胞摄取和持续释放。总体而言，UA修饰的MSN前药递送系统可以作为一种有前途的药物载体，用于提高UA的生物利用度，并进一步增强其抗癌功效。 (C) 2016 Elsevier B.V. 保留所有权利。
Ursolic acid (UA) as a nature product exhibits good anti-cancer activity, low toxicity, and good liver protection features. However, the low-solubility and poor bioavailability restrict its further clinical application. To overcome this problem, a pH-sensitive prodrug delivery system (UA@MSN-UA) that incorporated acid-sensitive linkage between drug and silica-based mesoporous nanosphere (MSN) was successfully designed and synthesized. The physicochemical properties of the UA@MSN-UA nanoparticles were investigated for shape, particle size, zeta potential, nitrogen adsorption-desorption and infrared (IR) spectroscopy. The nanoparticles were further evaluated for in vitro cytotoxicity, including proliferation inhibition, cell cycle distribution and apoptotic effects against human hepatocellular carcinoma HepG2 cells. The TEM image showed that the size of synthesized MSN nanoparticle was a near-spherical shapewith similar to 100 nm diameter. In vitro cytotoxicity testing demonstrated that UA@MSN-UA nanoparticles prodrug exhibited higher proliferation inhibition, cell cycle arrest at the G2/M phase and significantly caused the early and late apoptosis in HepG2 cells, which would be contributed to high loading capacity, high cellular uptake and sustained release of UA. Overall, the UA-modified MSN prodrug delivery system can be a promising drug carrier for improving the bioavailability of UA, and further enhance its anti-cancer efficacy. (C) 2016 Elsevier B.V. All rights reserved.