Folic acid-modified laponite nanodisks for targeted anticancer drug delivery

Folic acid-modified laponite nanodisks for targeted anticancer drug delivery
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用于靶向抗癌药物输送的叶酸修饰锂皂石纳米盘

DOI:
10.1039/c4tb01162g
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发表时间:
2014-01-01
影响因子:
7
通讯作者:
Shi, Xiangyang
Shi, Xiangyang
中科院分区:
工程技术2区
文献类型:
--
作者:
Wu, Yilun;Guo, Rui;Shi, Xiangyang

文献摘要

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我们在这里报告了一种有效的方法来修改锂皂石(锂皂石)与叶酸(FA)的靶向抗癌药物输送应用纳米盘。在该方法中,首先用3-氨基丙基二甲基乙氧基硅烷(APMES)修饰纳米盘以使其具有丰富的表面胺,然后通过1-乙基-3-(3-二甲基氨基丙基)碳二亚胺(EDC)化学与FA缀合。然后将形成的FA-修饰的纳米盘(LM-FA)用于包封抗癌药物阿霉素(DOX)。通过不同的技术,其特征在于纳米盘的表面改性和随后的药物封装在纳米盘内。我们表明,LM-FA能够以92.1 +/-2.2%的效率包封DOX,并且所形成的LM-FA/DOX复合物能够以pH依赖性方式释放DOX,在酸性pH条件下比在生理pH条件下具有更高的DOX释放速率。LM-FA中DOX的包封不损害其治疗活性。重要的是,形成的LM-FA/DOX复合物能够特异性靶向过表达高亲和力FA受体的癌细胞,如通过流式细胞术分析和共聚焦显微镜观察所证实的,并对靶癌细胞发挥特异性治疗功效。开发的FA修饰的纳米盘可能具有很大的希望,可用作不同抗癌药物的靶向递送的有效纳米平台。
We report here an effective approach to modifying laponite (LAP) nanodisks with folic acid (FA) for targeted anticancer drug delivery applications. In this approach, LAP nanodisks were first modified with 3-aminopropyldimethylethoxysilane (APMES) to render them with abundant surface amines, followed by conjugation with FA via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) chemistry. The formed FA-modified LAP nanodisks (LM-FA) were then used to encapsulate anticancer drug doxorubicin (DOX). The surface modification of LAP nanodisks and the subsequent drug encapsulation within the LAP nanodisks were characterized via different techniques. We show that the LM-FA is able to encapsulate DOX with an efficiency of 92.1 +/- 2.2%, and the formed LM-FA/DOX complexes are able to release DOX in a pH-dependent manner with a higher DOX release rate under acidic pH conditions than under physiological pH conditions. The encapsulation of DOX within LM-FA does not compromise its therapeutic activity. Importantly, the formed LM-FA/DOX complexes are able to specifically target cancer cells overexpressing high-affinity FA receptors as confirmed via flow cytometric analysis and confocal microscopic observation, and exert specific therapeutic efficacy to the target cancer cells. The developed FA-modified LAP nanodisks may hold great promise to be used as an efficient nanoplatform for targeted delivery of different anticancer drugs.