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透明质酸功能化的氧化还原响应免疫磁性纳米载体用于循环肿瘤细胞的捕获和释放。

Hyaluronic acid-functionalized redox responsive immunomagnetic nanocarrier for circulating tumor cell capture and release.

机构信息

School of Bioengineering and Food, Key Laboratory of Fermentation Engineering (Ministry of Education), Key Laboratory of Industrial Microbiology in Hubei, National '111' Center for Cellular Regulation and Molecular Pharmaceutics, Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei University of Technology, Wuhan 430068, People's Republic of China.

出版信息

Nanotechnology. 2021 Sep 1;32(47). doi: 10.1088/1361-6528/abdf8c.

DOI:10.1088/1361-6528/abdf8c
PMID:33494073
Abstract

Detection of circulating tumor cells (CTCs) in peripheral blood holds significant insights for cancer diagnosis, prognosis evaluation, and precision medicine. To efficiently capture and release CTCs with high viability, we reported the development of hyaluronic acid (HA)-functionalized redox responsive immunomagnetic nanocarrier (FeO@SiO-SS-HA). First, FeOnanoparticles were prepared and modified with tetraethyl orthosilicate (TEOS), 3-mercaptopropyltrimethoxysilane (MPTMS) and 2,2'-dithiodipyridine (DDPy) to form the magnetic substrate (FeO@SiO-SSPy). Modified with targeted segment HA-functionalized L-cysteine ethyl ester hydrochloride (HA-Cys) via disulfide exchange reaction, the FeO@SiO-SS-HA was formed. The nanocarrier with prominent magnetic property, targeting ligand, and redox-sensitive disulfide linkages was able to specially capture MCF-7 cells with an efficiency of 92% and effectively release captured cells with an efficiency of 81.4%. Furthermore, the FeO@SiO-SS-HA could successfully be used for the capture of MCF-7 cells, and the captured cells could be diferntiated from the blood cells. Almost all of released tumor cells kept good viability and a robust proliferative capacity after being re-cultured. It is likely that the as-prepared nanocarrier will serve as a new weapon against CD44 receptor-overexpressed cancer cells.

摘要

循环肿瘤细胞(CTC)在外周血中的检测对癌症的诊断、预后评估和精准医疗具有重要意义。为了高效捕获和释放具有高活力的 CTC,我们报道了一种基于透明质酸(HA)功能化的氧化还原响应免疫磁纳米载体(FeO@SiO-SS-HA)的开发。首先,制备了 FeO 纳米粒子,并通过四乙氧基硅烷(TEOS)、3-巯丙基三甲氧基硅烷(MPTMS)和 2,2'-二硫代二吡啶(DDPy)进行修饰,形成磁性基底(FeO@SiO-SSPy)。通过二硫键交换反应,用靶向片段 HA 功能化的 L-半胱氨酸乙酯盐酸盐(HA-Cys)对其进行修饰,形成 FeO@SiO-SS-HA。该纳米载体具有显著的磁性、靶向配体和氧化还原敏感的二硫键连接,能够特异性捕获 MCF-7 细胞,效率为 92%,并能够有效地以 81.4%的效率释放捕获的细胞。此外,FeO@SiO-SS-HA 可成功用于 MCF-7 细胞的捕获,且捕获的细胞可与血细胞区分开来。几乎所有释放的肿瘤细胞在重新培养后都保持良好的活力和强大的增殖能力。很可能,这种新制备的纳米载体将成为对抗 CD44 受体过表达癌细胞的新武器。

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