Targeted doxorubicin delivery to hepatocarcinoma cells by lactobionic acid-modified laponite nanodisks
Targeted doxorubicin delivery to hepatocarcinoma cells by lactobionic acid-modified laponite nanodisks
复制标题
通过乳糖酸修饰的合成锂皂石纳米盘将阿霉素靶向递送至肝癌细胞
DOI：
10.1039/c4nj01916d
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发表时间：
2015-01-01
影响因子：
3.3
通讯作者：
Guo, Rui
中科院分区：
文献类型：
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作者：
Chen, Guangxiang;Li, Du;Guo, Rui
在这项研究中，我们共价结合聚乙二醇连接的乳糖酸（PEG-LA）到锂皂石（LAPONY）纳米盘的表面上，用于靶向递送阿霉素（DOX）到肝癌细胞。首先用3-氨丙基二甲基乙氧基硅烷对纳米片进行表面修饰，在表面引入氨基基团，然后通过EDC化学方法成功地将PEG-LA偶联到纳米片上，形成靶向的LM-PEG-LA纳米片。最后，抗癌药物DOX被封装到合成的纳米载体中，具有91.5%的异常高的负载效率。体外释药研究表明，LM-PEG-LA/DOX在酸性条件下比在生理条件下具有更快的释药速度，且释药时间较长。MTT法结果表明，在相同DOX浓度下，LM-PEG-LA/DOX对肝癌细胞（HepG 2）的抑制作用明显高于非靶向药物。通过流式细胞仪和激光共聚焦显微镜进一步证实了LM-PEG-LA/DOX的靶向性。所开发的LA修饰的纳米盘可以作为靶向载体，用于高效装载和特异性递送不同的抗癌药物至肝癌细胞。
In this study, we covalently conjugated polyethylene glycol-linked lactobionic acid (PEG-LA) onto the surface of laponite (LAP) nanodisks for the targeted delivery of doxorubicin (DOX) to liver cancer cells. LAP nanodisks were firstly modified with 3-aminopropyldimethylethoxysilane to introduce amino groups on the surface, and then PEG-LA were successfully conjugated to form targeted LM-PEG-LA nanodisks via EDC chemistry. Finally, the anticancer drug DOX was encapsulated into the synthesized nanocarriers with an exceptionally high loading efficiency of 91.5%. In vitro release studies showed that LM-PEG-LA/DOX could release drugs in a sustained manner with a higher speed under acidic conditions than that under physiological ones. MTT assay results proved that LM-PEG-LA/DOX displayed a significant higher therapeutic efficacy in inhibiting the growth of hepatocellular carcinoma cells (HepG2 cells) than untargeted ones at the same DOX concentration. The targeting specificity of LM-PEG-LA/DOX was further demonstrated by flow cytometric analysis and confocal laser scanning microscopy. The developed LA-modified LAP nanodisks could serve as a targeted carrier for efficient loading and specific delivery of different anticancer drugs to liver cancer cells.