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载阿霉素的 AS1411 适体功能化白蛋白纳米粒偶联氧化铁和金纳米粒子的新型诊疗一体化系统

A novel theranostic system of AS1411 aptamer-functionalized albumin nanoparticles loaded on iron oxide and gold nanoparticles for doxorubicin delivery.

机构信息

Department of Chemistry, Yazd University, Yazd, Iran.

Department of Chemistry, Yazd University, Yazd, Iran.

出版信息

Int J Pharm. 2019 Jun 10;564:145-152. doi: 10.1016/j.ijpharm.2019.04.025. Epub 2019 Apr 9.

DOI:10.1016/j.ijpharm.2019.04.025
PMID:30978484
Abstract

Recently DNA aptamers have attracted remarkable attention as possible targeting ligands since selective targeting of cancer cells is a critical step in cancer diagnosis and therapy. Here, the development of AS1411 aptamer-functionalized albumin nanoparticles loaded on iron oxide and gold nanoparticles is reported for target delivery of the well-known anticancer drug of doxorubicin (Dox). Iron oxide nanoparticles (IONPs) and gold nanoparticles (GNPs) were prepared by ultrasound-assisted and controlled seeded growth synthetic methods, respectively. The nanocarrier was synthesized by a desolvation cross-linking method and characterized by dynamic light scattering, zeta potential measurement, thermogravimetric analysis, transmission electron microscopy, as well as vibrating sample magnetometer. The synthesized nanoparticles were found to be spherical with an average diameter of 120 nm and zeta potential of about -50.3 mV. The in-vitro anti-tumor effect of the designed delivery vehicle on MCF7 and SKBR3 human cancer cells was evaluated by MTT assay. The experimental results revealed that it could significantly inhibit the proliferation of cancerous cells. Moreover, GNPs and IONPs with the coating of albumin did not show any toxicity. AS1411 aptamer-functionalized nanoparticles improved cellular uptake and efficiency to MCF7 breast cancer cells as compared to non-targeting nanoparticles because of the high affinity of mentioned aptamer toward the overexpressed nucleolin on MCF7 cell surface.

摘要

最近,DNA 适体作为可能的靶向配体引起了人们的极大关注,因为选择性靶向癌细胞是癌症诊断和治疗的关键步骤。在这里,报告了载有氧化铁和金纳米粒子的 AS1411 适体功能化白蛋白纳米粒子的发展,用于靶向输送著名的抗癌药物阿霉素(Dox)。通过超声辅助和受控种子生长合成方法分别制备了氧化铁纳米粒子(IONP)和金纳米粒子(GNP)。纳米载体通过去溶剂交联法合成,并通过动态光散射、zeta 电位测量、热重分析、透射电子显微镜和振动样品磁强计进行了表征。所合成的纳米粒子呈球形,平均直径为 120nm,zeta 电位约为-50.3mV。通过 MTT 测定评估了设计的递送载体对 MCF7 和 SKBR3 人癌细胞的体外抗肿瘤作用。实验结果表明,它能显著抑制癌细胞的增殖。此外,具有白蛋白涂层的 GNPs 和 IONPs 没有显示出任何毒性。与非靶向纳米粒子相比,由于所述适体与 MCF7 细胞表面过表达的核仁素的高亲和力,AS1411 适体功能化纳米粒子提高了对 MCF7 乳腺癌细胞的细胞摄取和效率。

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