Nucleolin targeting AS1411 modified protein nanoparticle for antitumor drugs delivery.
Nucleolin targeting AS1411 modified protein nanoparticle for antitumor drugs delivery.
复制标题
DOI：
10.1021/mp300686g
复制
发表时间：
2013-08
影响因子：
4.9
通讯作者：
Jinhui Wu;Chenchen Song;Chenxiao Jiang;Xin Shen;Qian Qiao;Yiqiao Hu
中科院分区：
文献类型：
--
作者：
Jinhui Wu;Chenchen Song;Chenxiao Jiang;Xin Shen;Qian Qiao;Yiqiao Hu
近年来，细胞表面核仁素作为抗癌靶点引起了众多研究者的关注。为了提高抗肿瘤功效，我们开发了一种核仁素靶向蛋白纳米颗粒（NTPN）递送系统，其中人血清白蛋白（HSA）作为药物载体，并使用与核仁素具有高亲和力的DNA适体AS1411作为子弹。 HSA 纳米粒子 (NPs-PTX) 通过一种新颖的自组装方法制备，然后用 AS1411 (Apt-NPs-PTX) 进行修饰。所得 Apt-NPs-PTX 是球形的。与NPs-PTX相比，MCF-7细胞对Apt-NPs-PTX的摄取显着增加，而非肿瘤细胞系如MCF-10A和3T3细胞则减少。在一项细胞毒性研究中，Apt-NPs-PTX 在 MCF-7 肿瘤细胞中表现出增强的细胞毒性，而在 MCF-10A 细胞中几乎没有细胞毒性。核仁素抑制剂 Endostatin 可以显着降低 Apt-NPs-PTX 的内化，表明核仁素介导 Apt-NPs-PTX 的跨膜过程。因此，AS1411修饰的NTPN递送系统可能是一种有前途的靶向药物递送系统。
Over recent years, cell surface nucleolin as an anticancer target has attracted many researchers' attentions. To improve the antitumor efficacy, we developed a nucleolin targeted protein nanoparticle (NTPN) delivery system in which human serum albumin (HSA) was used as drug carrier and a DNA aptamer named AS1411, which had high affinity to nucleolin, was used as a bullet. The HSA nanoparticles (NPs-PTX) were fabricated by a novel self-assembly method and then modified with AS1411 (Apt-NPs-PTX). The resulted Apt-NPs-PTX were spherical. Compared with NPs-PTX, the uptake of Apt-NPs-PTX displayed a significant increase in MCF-7 cells while there was a decrease in nontumor cell lines such as MCF-10A and 3T3 cells. In a cytotoxic study, Apt-NPs-PTX displayed an enhanced cytotoxicity in MCF-7 tumor cells while there was almost no cytotoxicity in MCF-10A cells. Endostatin, a nucleolin inhibitor, could significantly decrease the internalization of Apt-NPs-PTX, suggesting nucleolin mediates the transmembrane process of Apt-NPs-PTX. Therefore, the AS1411 modified NTPN delivery system might be a promising targeted drug delivery system.