Branched polyethyleneimine modified with hyaluronic acid via a PEG spacer for targeted anticancer drug delivery
Branched polyethyleneimine modified with hyaluronic acid via a PEG spacer for targeted anticancer drug delivery
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DOI：
10.1039/c5ra23022e
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发表时间：
2016-01-01
期刊：
影响因子：
3.9
通讯作者：
Shi, Xiangyang
中科院分区：
文献类型：
--
作者：
Chen, Chen;Zhou, Benqing;Shi, Xiangyang
通常需要开发一种纳米载体系统，该系统能够改善抗癌药物的水溶性，并能够通过受体介导的内吞作用将药物靶向输送到癌细胞。在本工作中，聚乙烯亚胺(PEI)依次被双官能团聚乙二醇(NH2-PEGCOOH)、透明质酸(HA)和异硫氰酸荧光素(FI)修饰。然后将制备的PEI-FI-(PEG-HA)结合物作为纳米平台包埋抗癌药物阿霉素(DOX)。我们发现，形成的PEI-FI-(PEG-HA)结合物能够在每个多功能PEI中包裹大约19个DOX分子，并且形成的PEI-FI-(PEG-HA)/DOX络合物可以pH依赖的方式释放DOX，并且在酸性pH条件下比在生理pH条件下有更高的DOX释放速率。此外，经流式细胞仪分析和共聚焦显微镜观察证实，PEI-FI-(PEG-HA)/DOX复合体能够特异性地靶向高表达CD44受体的癌细胞，从而将DOX输送到靶细胞以抑制其生长。所开发的HA靶向PEI有望成为靶向输送不同抗癌药物的高效纳米平台。
It is generally required to develop a nanocarrier system that is able to improve the water solubility of an anticancer drug and enable targeted delivery of the drug to cancer cells via a receptor-mediated endocytosis pathway. In this work, polyethyleneimine (PEI) was sequentially modified with dual functional polyethylene glycol (NH2-PEG-COOH), hyaluronic acid (HA), and fluorescein isothiocyanate (FI). The prepared PEI-FI-(PEG-HA) conjugate was then used as a nanoplatform to encapsulate the anticancer drug doxorubicin (DOX). We show that the formed PEI-FI-(PEG-HA) conjugate is able to encapsulate approximately 19 DOX molecules within each multifunctional PEI, and the formed PEI-FI-(PEG-HA)/DOX complexes can release DOX in a pH-dependent manner with a higher DOX release rate under an acidic pH condition than under a physiological pH condition. In addition, the PEI-FI-(PEG-HA)/DOX complexes are able to specifically target cancer cells overexpressing CD44 receptors as confirmed via flow cytometric analysis and confocal microscopic observation, and thus deliver DOX to the target cancer cells to inhibit their growth. The developed HA-targeted PEI may hold great promise to be used as an efficient nanoplatform for the targeted delivery of different anticancer drugs.