Smart AS1411-aptamer conjugated pegylated PAMAM dendrimer for the superior delivery of camptothecin to colon adenocarcinoma in vitro and in vivo
Smart AS1411-aptamer conjugated pegylated PAMAM dendrimer for the superior delivery of camptothecin to colon adenocarcinoma in vitro and in vivo
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DOI：
10.1016/j.ijpharm.2017.01.044
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发表时间：
2017-03-15
影响因子：
5.8
通讯作者：
Ramezani, Mohammad
中科院分区：
文献类型：
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作者：
Alibolandi, Mona;Taghdisi, Seyed Mohammad;Ramezani, Mohammad
在目前的研究中，喜树碱负载的聚乙二醇PAMAM树突状分子被AS1411抗核蛋白适配体功能化，用于靶向过表达核蛋白受体的结直肠癌细胞。利用透射电子显微镜（TEM）和DLS对制备的纳米颗粒的形貌和粒径分散性进行了表征。载药量和包封率分别为8.1%和93.67%。喜树碱的体外释放量为包封的喜树碱4天的缓释量。体外细胞毒性对比实验表明，靶向喜树碱负载聚乙二醇树突状物对核蛋白阳性的HT29和C26结直肠癌细胞比核蛋白阴性的CHO细胞株具有更高的抗增殖活性。荧光显微镜和流式细胞术也证实了AS1411靶向聚乙二醇树状大分子的细胞摄取增强。在C26荷瘤BALB/C小鼠的体内研究表明，as1411功能化的喜树碱负载聚乙二醇树状大分子提高了包封的喜树碱的抗肿瘤活性和存活率。AS1411适体与喜树碱负载的聚乙二醇树状分子表面结合，提供喜树碱的位点特异性递送，抑制C26肿瘤的体内生长，显著降低全身毒性。这些结果表明，新的以核蛋白为靶点的聚乙二醇化PAMAM树状大分子作为喜树碱的递送系统具有治疗核蛋白过表达的结直肠癌的潜力。(C) 2017 Elsevier B.V.版权所有
In the current study camptothecin-loaded pegylated PAMAM dendrimer were synthesized and were functionalized with AS1411 anti-nucleolin aptamers for site-specific targeting against colorectal cancer cells which over expresses nucleolin receptors.The morphological properties and size dispersity of the prepared nanoparticles were evaluated using transmission electron microscope (TEM) and DLS. The drug-loading content and encapsulation efficiency were obtained 8.1% and 93.67% respectively. The in vitro release of camptothecin from the formulation was provided the sustained release of encapsulated camptothecin during 4 days. Comparative in vitro cytotoxicity experiments demonstrated that the targeted camptothecin loaded-pegylated dendrimers had higher antiproliferation activity, towards nucleolin-positive HT29 and C26 colorectal cancer cells than nucleolin-negative CHO cell line.Fluorscence microscopy and flow cytometry also confirmed the enhanced cellular uptake of AS1411 targeted pegylated-dendrimer. In vivo study in C26 tumor-bearing BALB/C mice revealed that the AS1411-functionalized camptothecin loaded pegylated dendrimers improved antitumor activity and survival rate of the encapsulated camptothecin. Conjugation of AS1411 aptamer to the camptothecin loaded-pegylated dendrimer surface provides site-specific delivery of camptothecin, inhibit C26 tumor growth in vivo and significantly decrease systemic toxicity. These results suggested that the new nucleolin-targeted pegylated PAMAM dendrimer as a delivery system for camptothecin have the potential for the treatment of nucleolin-overexpressed colorectal cancer. (C) 2017 Elsevier B.V. All rights reserved.