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新型适配体引导的磁性纳米颗粒增强对EpCAM阳性肿瘤细胞的热损伤

[Enhancement of thermal damage to EpCAM-positive tumor cells by novel aptamer-guided magnetic nanoparticles].

作者信息

Zhang L Y, Wang M, Wu H B, Yang Y, Li Q, Sun H L

机构信息

Shanxi Institute of Pediatric Diseases, Xi'an Children's Hospital, Xi'an 710002, China.

Department of Orthopaedics, 11 Military Hospital of China, Yining 835000, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2017 Oct 23;39(10):726-731. doi: 10.3760/cma.j.issn.0253-3766.2017.10.002.

Abstract

To explore the thermal damage to epithelial cell adhesion molecule(EpCAM)-positive tumor cells by novel aptamer-guided magnetic nanoparticles(AptNPs). EpCAM aptamer SYL3C was connected to NPs via biotin-streptavidin reaction. The diameter of AptNPs were characterized by Dynamic Light Scattering(DLS). The binding feature of the aptamer to EpCAM-positive tumor cells was evaluated by Prussian blue dyeing. Thermal damage under alternative magnetic field was measured bylactate dehydrogenase (LDH). The apoptosis of EpCAM-positive tumor cells was detected by acridine orange/ethidium bromide (AO/EB) double staining. The average size of AptNPs was 282 nm. Flow cytometry and Prussian blue dyeing showed that AptNPs exhibited strong binding to the EpCAM-positive tumor cells but not to the EpCAM-negative tumor cells. Moreover, when incubated with 1.5×10(8) AptNPs under alternative electromagnetic fieldfor 5 hours, the viability of EpCAM-positive HCT116 cells and A549 cells was 28.9% and 54.4%, respectively, significantly lower than 76.7% of EpCAM-negative HepG2 cells (<0.05). AptNPs can improve the thermal damage to EpCAM-positive tumor cells, and may have potential utility in the development of tumor targeted therapy.

摘要

探索新型适配体导向磁性纳米颗粒(AptNPs)对上皮细胞黏附分子(EpCAM)阳性肿瘤细胞的热损伤作用。通过生物素-链霉亲和素反应将EpCAM适配体SYL3C连接到纳米颗粒上。采用动态光散射(DLS)法表征AptNPs的直径。通过普鲁士蓝染色评估适配体与EpCAM阳性肿瘤细胞的结合特性。用乳酸脱氢酶(LDH)检测交变磁场下的热损伤。采用吖啶橙/溴化乙锭(AO/EB)双染法检测EpCAM阳性肿瘤细胞的凋亡情况。AptNPs的平均粒径为282 nm。流式细胞术和普鲁士蓝染色显示,AptNPs与EpCAM阳性肿瘤细胞有强烈结合,而与EpCAM阴性肿瘤细胞无结合。此外,当在交变电磁场下与1.5×10⁸个AptNPs孵育5小时后,EpCAM阳性的HCT116细胞和A549细胞的活力分别为28.9%和54.4%,显著低于EpCAM阴性的HepG2细胞的76.7%(P<0.05)。AptNPs可增强对EpCAM阳性肿瘤细胞的热损伤作用,在肿瘤靶向治疗的研发中可能具有潜在应用价值。

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