A multi-storey DNA nanostructure containing doxorubicin and AS1411 aptamer for targeting breast cancer cells

适体 纳米结构 核仁素 细胞毒性 阿霉素 DNA 癌细胞 流式细胞术 MTT法 体内 化学 分子生物学 生物物理学 纳米技术 细胞 材料科学 体外 生物化学 生物 癌症 化疗 遗传学 细胞质 核仁
作者
Elnaz Yaghoobi,Taraneh Sadat Zavvar,Mohammad Ramezani,Mona Alibolandi,Sara Rahimzadeh Oskuei,Mahsa Zahiri,Morteza Alinezhad Nameghi,Khalil Abnous,Seyed Mohammad Taghdisi
出处
期刊:Journal of Drug Targeting [Taylor & Francis]
卷期号:: 1-7 被引量:12
标识
DOI:10.1080/1061186x.2022.2094387
摘要

Herein, we presented a novel DOX-loaded multi-storey DNA nanostructure, including AS1411 aptamer as a targeting agent for treatment of target cells (MCF-7 and 4T1). Gel retardation test and fluorometric analysis were used to examine the construction of DNA nanostructure and loading of DOX in the complex. At pH 5.5 and 7.4, the release patterns of DOX from the prepared formulation were studied. Cell viability test was conducted to analyse the cell cytotoxicity ability of the DOX loaded multi-storey DNA nanostructure compared to free DOX in 4T1, MCF-7 (target) and CHO cells (non-target). Flow cytometry analysis was used to examine the DOX-loaded DNA nanostructure internalisation. Finally, the developed DOX-loaded multi-storey DNA nanostructure was tested in vivo to see if it could prevent tumour growth. The drug was released from the nanocomplex in a pH-related process (higher release in acidic pH compared to neutral pH). According to MTT assay, DOX-loaded DNA nanostructure damaged nucleolin positive cells while not significantly affecting nucleolin negative cells. The formulation was efficaciously internalised into target cells (4T1 and MCF-7), but not into non-target ones. Moreover, DOX-loaded DNA nanostructure can restrict tumour growth, increase survival rate, and accumulate significantly more in the tumour site than free DOX.
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