期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 519, 期 1-2, 页码 250-262出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2017.01.031
关键词
Arsenic trioxide; Hollow mesoporous silica nanoparticles; Liposomal shell; Arg-Gly-Asp; Controlled release; Hepatic carcinoma
资金
- National Science Foundation of China [81274089, 81473361, 81373982, 81673607, 81303235]
- Natural Science Foundation of Zhejiang Province [LZ13H280001]
- Traditional Chinese Medicine Science and Technology Plan of Zhejiang Province [2016ZA130]
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.
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