title: RGD conjugated liposome-hollow silica hybrid nanovehicles for targeted and controlled delivery of arsenic trioxide against hepatic carcinoma.
abstract: 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 (IC50) value. In pharmacokinetic studies, the RGD-LP-CHMSN-ATO group, compared to the free ATO group, prolonged the half time (t1/2β) 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.
authors.affiliation: College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Fei
authors.affiliation: College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
authors.forename: Shunping
authors.initials: S
authors.lastname: Han
authors.affiliation: College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
authors.forename: Jiaoyang
authors.initials: J
authors.lastname: Tao
authors.affiliation: Libraries of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
authors.forename: Hongyue
authors.initials: H
authors.lastname: Zheng
authors.affiliation: College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Wei
authors.affiliation: College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
authors.forename: Jiazhen
authors.initials: J
authors.lastname: Zhu
authors.affiliation: College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China. Electronic address: lifanzhu@zcmu.edu.cn.
authors.forename: Fanzhu
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, 116027, China. Electronic address: 542695603@qq.com.
authors.forename: Xuanshen
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000737:chemistry* / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry*; D008113:Liver Neoplasms / Q000188:drug therapy; D061986:MCF-7 Cells; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D010087:Oxides / Q000737:chemistry* / Q000494:pharmacology; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008081:Liposomes; D009842:Oligopeptides; D010087:Oxides; D012822:Silicon Dioxide; C047981:arginyl-glycyl-aspartic acid; D000077237:Arsenic Trioxide
keywords: Arg-Gly-Asp; Arsenic trioxide; Controlled release; Hepatic carcinoma; Hollow mesoporous silica nanoparticles; Liposomal shell