Aptamer-Modified Tetrahedral DNA Nanostructure for Tumor-Targeted Drug Delivery
Aptamer-Modified Tetrahedral DNA Nanostructure for Tumor-Targeted Drug Delivery
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用于肿瘤靶向药物输送的适体修饰四面体 DNA 纳米结构
DOI：
10.1021/acsami.7b13328
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发表时间：
2017-10-25
影响因子：
9.5
通讯作者：
Lin, Yunfeng
中科院分区：
文献类型：
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作者：
Li, Qianshun;Zhao, Dan;Lin, Yunfeng
四面体DNA纳米结构具有良好的生物相容性和生物可降解性，被认为是一种很有前途的药物载体。此外，它们可以被官能团修饰。为了提高TDNs的给药能力，我们选择抗癌适体AS 1411对TDNs进行修饰，用于肿瘤靶向给药。AS 1411可与肿瘤细胞膜上过表达的核仁素特异性结合。此外，AS 1411还能抑制NF-κ B B信号通路，降低bcl-2的表达。在本研究中，我们比较了缺氧条件下AS 1411修饰的TDNs（Apt-TDNs）和TDNs在不同细胞中的细胞内定位。此外，我们还比较了Apt-TDNs和TDNs在缺氧条件下对细胞生长和细胞周期的影响。Apt-TDNs大量进入MCF-7细胞核并聚集，而进入L929细胞的Apt-TDNs数量相对较少，MCF-7细胞中TDNs的进入量远低于Apt-TDNs。此外，进入L929细胞和MCF-7细胞的TDNs的量几乎没有差异。Apt-TDNs可抑制MCF-7细胞生长并促进L929细胞生长，而TDNs可促进MCF-7和L929细胞生长。因此，结果表明Apt-TDNs是比TDNs更有效的肿瘤靶向药物递送载体，具有特异性抑制肿瘤细胞生长的能力。
Tetrahedral DNA nanostructures (TDNs) are considered promising drug delivery carriers because they are able to permeate cellular membrane and are biocompatible and biodegradable. Furthermore, they can be modified by functional groups. To improve the drug-delivering ability of TDNs, we chose anticancer aptamer AS1411 to modify TDNs for tumor-targeted drug delivery. AS1411 can specifically bind to nucleolin, which is overexpressed on the cell membrane of tumor cells. Furthermore, AS1411 can inhibit NF-kappa B signaling and reduce the expression of bcl-2. In this study, we compared the intracellular localization of AS1411-modified TDNs (Apt-TDNs) with that of TDNs in different cells under hypoxic condition. Furthermore, we compared the effects of Apt-TDNs and TDNs on cell growth and cell cycle under hypoxic condition. A substantial amount of Apt-TDNs entered and accumulated in the nucleus of MCF-7 cells; however, the amount of Apt-TDNs that entered L929 cells was comparatively less. TDNs entered in much lower quantity in MCF-7 cells than Apt-TDNs. Moreover, there was little difference in the amount of TDNs that entered L929 cells and MCF-7 cells. Apt-TDNs can inhibit MCF-7 cell growth and promote L929 cell growth, while TDNs can promote both MCF-7 and L929 cell growth. Thus, the results indicate that Apt-TDNs are more effective tumor-targeted drug delivery vehicles than TDNs, with the ability to specifically inhibit tumor cell growth.