XAV939: From a Small Inhibitor to a Potent Drug Bioconjugate When Delivered by Gold Nanoparticles

被引：27

作者：

Afifi, Marwa M. ^{[1
]}

Austin, Lauren A. ^{[1
]}

Mackey, Megan A. ^{[1
]}

El-Sayed, Mostafa A. ^{[1
]}

机构：

[1] Georgia Inst Technol, Sch Chem & Biochem, Laser Dynam Lab, Atlanta, GA 30332 USA

来源：

BIOCONJUGATE CHEMISTRY | 2014年 / 25卷 / 02期

基金：

美国国家卫生研究院;

关键词：

CELL-CYCLE CONTROL; SIGNALING PATHWAY; SIZE; WNT; CANCER; CYTOTOXICITY; ACTIVATION; ADSORPTION; EFFICIENCY; THERAPY;

D O I：

10.1021/bc400271x

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Nanoparticles as potential drug delivery vectors are drawing more attention every day. Here, we used gold nanopspheres (AuNSs) to selectively target the Wnt signaling pathway in human oral squamous cell carcinoma (HSC-3) cells. In a previously conducted study, XAV939, a small inhibiter, was found to strongly regulate the Wnt pathway by inhibiting the tankyrase enzyme and subsequent stabilization of cytoplasmic axin levels. In the present study, conjugating XAV939 molecules to AuNSs is found to enhance its potency by at least 100 times over its free form in killing HSC-3 cancer cells. Additionally, XAV 939 uptake studies have demonstrated an enhanced XAV939 bioconjugate delivery to the targeted cells compared to the passive cellular diffusion of the free drug at the same concentration. Furthermore, our study revealed that drug delivery and cytotoxicity are directly related to the size of the functionalized nanoparticles.

引用

页码：207 / 215

页数：9

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