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载有阿霉素的DNA适配体连接肉豆蔻酰化壳聚糖纳米凝胶用于前列腺癌的靶向给药

Doxorubicin Loaded DNA Aptamer Linked Myristilated Chitosan Nanogel for Targeted Drug Delivery to Prostate Cancer.

作者信息

Atabi Fereshteh, Mousavi Gargari Seyed Latif, Hashemi Mehrdad, Yaghmaei Parichehreh

机构信息

Department of Biology, Science and research branch, Islamic Azad University, Tehran, Iran.

Department of Biology, Faculty of Science, Shahed University, Tehran, Iran.

出版信息

Iran J Pharm Res. 2017 Winter;16(1):35-49.

Abstract

Recently, specific attention has been paid to aptamers, short DNA or RNA, as a tool for cancer diagnosis and therapy. In the present study MCS nanogels were prepared by Myristate: Chitosan at 1:9 ratio and were characterized by several techniques. A selected ssDNA aptamer (Apt) capable of detecting LNCaP cells was linked to Myristilated Chitosan nanogels (Apt-MCS) by glutaraldehyde and loaded with Doxorubicin (DOX) to be used in targeted drug delivery against the Prostate cancer cells. LNCaP and PC-3 cells were treated with Apt-MCS-DOX complex and the binding efficiency was estimated by flow cytometry. The binding affinity of the selected aptamers was above 70% compared to the initial library. The loading capacity of the nanogel was as high as 97% and up to 40% of DOX were released from MCS within 15 days. Cytotoxicity of nanodrug on LNCaP cells was determined by MTT assay. Apt-MCS-DOX was specifically binded to LNCaP cells whereas it didn't show any specificity to PC-3 cells as a negative control. Both MCS-DOX and Apt-MCS-DOX showed a lethal effect on LNCaP cells. Our results can lead to an aptamer based simple and applicable technique for early diagnosis and treatment of cancerous cells.

摘要

最近,适配体(短DNA或RNA)作为一种癌症诊断和治疗工具受到了特别关注。在本研究中,以肉豆蔻酸与壳聚糖1:9的比例制备了MCS纳米凝胶,并通过多种技术对其进行了表征。一种能够检测LNCaP细胞的选定单链DNA适配体(Apt)通过戊二醛与肉豆蔻酰化壳聚糖纳米凝胶(Apt-MCS)相连,并负载阿霉素(DOX),用于针对前列腺癌细胞的靶向药物递送。用Apt-MCS-DOX复合物处理LNCaP和PC-3细胞,并通过流式细胞术评估结合效率。与初始文库相比,选定适配体的结合亲和力高于70%。纳米凝胶的负载能力高达97%,15天内高达40%的DOX从MCS中释放出来。通过MTT法测定纳米药物对LNCaP细胞的细胞毒性。Apt-MCS-DOX特异性结合LNCaP细胞,而作为阴性对照,它对PC-3细胞没有任何特异性。MCS-DOX和Apt-MCS-DOX对LNCaP细胞均显示出致死作用。我们的结果可以导致一种基于适配体的简单且适用的技术,用于癌细胞的早期诊断和治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7885/5423232/b9cb2ac4737c/ijpr-16-035-g001.jpg

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