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使用两种不同的适体 - 功能化纳米颗粒对乳腺癌细胞进行靶向成像。

Targeted imaging of breast cancer cells using two different kinds of aptamers -functionalized nanoparticles.

机构信息

Department of Chemistry, Payame Noor University, 19395-4697 Tehran, Iran; Student Research Committee (SRC), Mashhad University of Medical Sciences, Mashhad, Iran; Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Eur J Pharm Sci. 2019 Jun 15;134:60-68. doi: 10.1016/j.ejps.2019.04.012. Epub 2019 Apr 7.

Abstract

Breast cancer which is the most commonly diagnosed cancer among women; have been known as a serious threat for health and life around the world. So development of an approach for early-stage diagnosis of breast cancer is vital. In this study, we designed a double aptamer-nanoparticle conjugates-based (DANP) complex for specific detection and visualization of MCF-7 cells using Mucin 1 (MUC 1) aptamer-conjugated gold nanoparticles (MUC1 apt - GNPs) and adenosine triphosphate (ATP) aptamer-conjugated CdTe quantum dots (ATP apt-QDs). The ATP apt-QDs was attached onto MUC1 apt - GNPs surface through Van der Waals forces and electrostatic interactions between ATP aptamer and GNPs leading to the formation of DANP complex. Atomic force microscopy asserted DANP complex formation. The imaging process was based on the recognition of MUC1 protein on the surface of MCF-7 cells by MUC1 aptamer and specific internalization of DANP complex into target cells (MCF-7). Existence of abundant amounts of ATP in lysosome led to release of ATP apt-QDs from the MUC1 apt-GNPs surface resulting in strong fluorescence emission. The flow cytometry analysis and fluorescence microscopy confirmed significant internalization of DANP complex into MCF-7 cells (target) in comparison with CHO cells (non-target). Based on the obtained results, the DANP complex possesses high potency for efficient detection and monitoring of breast cancer cells (MCF-7).

摘要

乳腺癌是女性最常见的癌症;已被公认为全球范围内对健康和生命的严重威胁。因此,开发早期诊断乳腺癌的方法至关重要。在这项研究中,我们设计了一种双适体-纳米颗粒偶联物(DANP)复合物,使用粘蛋白 1(MUC 1)适体偶联金纳米颗粒(MUC1 apt - GNPs)和三磷酸腺苷(ATP)适体偶联碲化镉量子点(ATP apt-QDs)特异性检测和可视化 MCF-7 细胞。ATP apt-QDs 通过范德华力和 ATP 适体与 GNPs 之间的静电相互作用附着在 MUC1 apt - GNPs 表面上,导致 DANP 复合物的形成。原子力显微镜证实了 DANP 复合物的形成。成像过程基于 MUC1 适体对 MCF-7 细胞表面上 MUC1 蛋白的识别以及 DANP 复合物特异性内化进入靶细胞(MCF-7)。溶酶体中大量 ATP 的存在导致 ATP apt-QDs 从 MUC1 apt-GNPs 表面释放,从而产生强烈的荧光发射。流式细胞术分析和荧光显微镜证实 DANP 复合物与 CHO 细胞(非靶细胞)相比,大量内化到 MCF-7 细胞(靶细胞)中。基于所得结果,DANP 复合物具有高效检测和监测乳腺癌细胞(MCF-7)的高潜力。

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