Xia Wenxi, Shangguan Xiaoyan, Li Miao, Wang Yang, Xi Dongmei, Sun Wen, Fan Jiangli, Shao Kun, Peng Xiaojun
State Key Laboratory of Fine Chemicals, Dalian University of Technology Dalian 116024 China
School of Biological Engineering, Dalian Polytechnic University Ganjingzi District Dalian 116034 PR China.
Chem Sci. 2020 Dec 22;12(9):3314-3321. doi: 10.1039/d0sc05112h.
The detection of the circulating tumor cells (CTCs) detached from solid tumors has emerged as a burgeoning topic for cancer diagnosis and treatment. The conventional CTC enrichment and identification mainly rely on the specific binding of the antibodies on the capture interface of the magnetic nanoparticles with the corresponding biomarkers on the cell membranes. However, these methods could easily generate false-negative results due to the extremely low concentration of CTCs and the internal heterogeneity of the tumor cells. Herein, with the aim of selectively identifying CTCs and improving the detection accuracy in peripheral blood, we designed the fluorometric "turn on" Au nanoparticles (DHANs) with the modification of a tumor-targeted moiety, dehydroascorbic acid (DHA) and a fluorometric aptamer, which could be "switched-on" by an over-expressed intracellular protein, namely hypoxia-inducible factor-1α (HIF 1α). This novel nanoformulated detection platform demonstrated the great capacity for visualizing various CTCs in peripheral blood with significantly improved detection efficiency and sensitivity. As a result, the nanoplatform has a great potential to be further applied for CTC detection or , which holds promise for extensive CTC studies.
从实体瘤中分离出的循环肿瘤细胞(CTCs)的检测已成为癌症诊断和治疗中一个新兴的研究课题。传统的CTCs富集和鉴定主要依赖于磁性纳米颗粒捕获界面上的抗体与细胞膜上相应生物标志物的特异性结合。然而,由于CTCs浓度极低以及肿瘤细胞的内在异质性,这些方法很容易产生假阴性结果。在此,为了选择性地识别CTCs并提高外周血中的检测准确性,我们设计了一种荧光“开启”金纳米颗粒(DHANs),其修饰了肿瘤靶向部分脱氢抗坏血酸(DHA)和一种荧光适配体,该适配体可被过度表达的细胞内蛋白即缺氧诱导因子-1α(HIF 1α)“开启”。这种新型的纳米检测平台展示了在外周血中可视化各种CTCs的强大能力,检测效率和灵敏度显著提高。因此,该纳米平台具有进一步应用于CTCs检测的巨大潜力,有望推动广泛的CTCs研究。