XAV939：当通过金纳米粒子递送时，从小抑制剂到有效药物偶联物。
XAV939: from a small inhibitor to a potent drug bioconjugate when delivered by gold nanoparticles.
机构信息
Laser Dynamic Laboratory, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332-0400, United States.
出版信息
Bioconjug Chem. 2014 Feb 19;25(2):207-215. doi: 10.1021/bc400271x. Epub 2014 Jan 10.
Abstract
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.
摘要
纳米粒子作为潜在的药物输送载体，正日益受到关注。在这里，我们使用金纳米球（AuNSs）来选择性地靶向人口腔鳞状细胞癌细胞（HSC-3）中的 Wnt 信号通路。在之前的一项研究中，发现小分子抑制剂 XAV939 通过抑制 tankyrase 酶和随后稳定细胞质轴蛋白水平来强烈调节 Wnt 通路。在本研究中，将 XAV939 分子与 AuNSs 连接，发现其在杀死 HSC-3 癌细胞方面的效力比游离形式至少增强了 100 倍。此外，XAV939 摄取研究表明，与相同浓度下游离药物的被动细胞扩散相比，靶向细胞对 XAV939 生物缀合物的摄取得到了增强。此外，我们的研究表明，药物输送和细胞毒性与功能化纳米粒子的大小直接相关。
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