RGD conjugated liposome-hollow silica hybrid nanovehicles for targeted and controlled delivery of arsenic trioxide against hepatic carcinoma
RGD conjugated liposome-hollow silica hybrid nanovehicles for targeted and controlled delivery of arsenic trioxide against hepatic carcinoma
复制标题
RGD 缀合脂质体-空心二氧化硅杂化纳米载体用于靶向和控制三氧化二砷抗肝癌的递送
DOI：
10.1016/j.ijpharm.2017.01.031
复制
发表时间：
2017-03-15
影响因子：
5.8
通讯作者：
Wang, Xuanshen
中科院分区：
文献类型：
--
作者：
Fei, Weidong;Zhang, Yan;Wang, Xuanshen
摘要本研究旨在构建arg - gy - asp （RGD）偶联脂质体-中空二氧化硅复合纳米载体，用于靶向递送和控释三氧化二砷（ATO），其抗实体肿瘤作用受到药代动力学差和剂量限制毒性的影响。利用疏水相互作用将完整的脂膜附着在氯二甲基十八烷基硅烷修饰的中空介孔二氧化硅纳米颗粒表面。制备的纳米载体（RGD-LP-CHMSN）结构均匀（硅核直径约为140 nm，脂质体壳直径约为6 nm），载药效率为6.76%，稳定性好，控释效果好。RGD-LPCHMSN在体外对HepG2、MCF-7和LO2细胞具有良好的生物相容性和低毒性。通过纳米载体（RGD-LP-CHMSN-ATO）靶向递送ATO，证明了细胞摄取增强和最大抑制浓度（IC50）值降低了一半。在药代动力学研究中，RGD-LP-CHMSN-ATO组与游离ATO组相比，半衰期（t(1/2 beta)）延长了1.7倍，曲线下面积（AUC）增加了2.4倍。除了;在H22肿瘤-异种移植小鼠模型中，纳米载体提高了ATO的靶向效率和抗癌潜力。综上所述，构建具有靶向递送和控释特性的纳米载体策略有望增强ATO的抗肿瘤作用。(C) 2017 Elsevier B.V.版权所有
The aim of our study was to construct an Arg-Gly-Asp (RGD)-conjugated liposome-hollow silica hybrid nanovehicle for targeted delivery and controlled release of arsenic trioxide (ATO), whose anti-solid tumor effect was hampered by poor pharmacokinetics and dose-limited toxicity. Hydrophobic interactions were used to attach intact lipid membrane to the surface of chlorodimethyloctadecylsilane-modified hollow mesoporous silica nanoparticles. The prepared nanovehicles (RGD-LP-CHMSN) were characterized for uniform structure (silica core of similar to 140 nm in diameter and liposomal shell of 6 nm), comparable drug loading efficiency (6.76%), desirable stability and strengthened controlled release. In vitro, RGD-LPCHMSN showed good biocompatibility and low toxicity on HepG2, MCF-7 and LO2 cells. The targeted delivery of ATO by nanocarriers (RGD-LP-CHMSN-ATO) was demonstrated by an enhanced cellular uptake and a reduced half maximal inhibitory concentration (IC50) value. In pharmacokinetic studies, the RGD-LP-CHMSN-ATO group, compared to the free ATO group, prolonged the half time (t(1/2 beta)) by 1.7 times and increased the area under curve (AUC) by 2.4 times. In addition; in a H22 tumor-xenograft mouse model, nanovehicles improved the targeting efficiency and anticancer potential of ATO. In conclusion, the strategy of constructing a nanocarrier with targeted delivery and controlled release characteristics is prospective to enhance the antitumor effect of ATO. (C) 2017 Elsevier B.V. All rights reserved.