Fei Weidong, Zhang Yan, Han Shunping, Tao Jiaoyang, Zheng Hongyue, Wei Yinghui, Zhu Jiazhen, Li Fanzhu, Wang Xuanshen
College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Libraries of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Int J Pharm. 2017 Mar 15;519(1-2):250-262. doi: 10.1016/j.ijpharm.2017.01.031. Epub 2017 Jan 18.
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 ∼140nm in diameter and liposomal shell of ∼6nm), comparable drug loading efficiency (6.76%), desirable stability and strengthened controlled release. In vitro, RGD-LP-CHMSN 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 (IC) value. In pharmacokinetic studies, the RGD-LP-CHMSN-ATO group, compared to the free ATO group, prolonged the half time (t) 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.
我们研究的目的是构建一种用于靶向递送和控制释放三氧化二砷（ATO）的精氨酸-甘氨酸-天冬氨酸（RGD）偶联脂质体-中空二氧化硅杂化纳米载体，三氧化二砷的抗实体瘤作用因药代动力学不佳和剂量限制性毒性而受到阻碍。利用疏水相互作用将完整的脂质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。对制备的纳米载体（RGD-LP-CHMSN）进行表征，其结构均匀（二氧化硅核心直径约为140nm，脂质体外壳约为6nm），载药效率相当（6.76%），稳定性良好且控释性能增强。在体外，RGD-LP-CHMSN对HepG2、MCF-7和LO2细胞表现出良好的生物相容性和低毒性。纳米载体（RGD-LP-CHMSN-ATO）对ATO的靶向递送通过增强细胞摄取和降低半数最大抑制浓度（IC）值得到证明。在药代动力学研究中，与游离ATO组相比，RGD-LP-CHMSN-ATO组的半衰期（t）延长了1.7倍，曲线下面积（AUC）增加了2.4倍。此外，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。总之，构建具有靶向递送和控释特性的纳米载体的策略对于增强ATO的抗肿瘤作用具有前瞻性。
