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PreS1 肽功能化金纳米结构与 SERRS 标签用于高效肝癌细胞靶向

PreS1 peptide-functionalized gold nanostructures with SERRS tags for efficient liver cancer cell targeting.

机构信息

Department of Chemical Sciences, University of Padova, via F. Marzolo 1, 35131 Padova, Italy.

Department of Medicine, University of Padova, via N. Giustiniani 2, 35128 Padova, Italy.

出版信息

Mater Sci Eng C Mater Biol Appl. 2019 Oct;103:109762. doi: 10.1016/j.msec.2019.109762. Epub 2019 May 16.

Abstract

Early detection is the most effective mean of improving prognosis for many fatal diseases such as cancer. In this context, the Surface Enhanced Resonance Raman Scattering (SERRS) technique is being proposed as alternative to fluorescent methods in detection of biomarkers, because SERRS nanostructures are bright as fluorescent tags but more stable and clearly detectable using the narrow Raman "fingerprints" of a suitable reporter. Here we show that biocompatible SERRS active gold nanostructures, functionalized with an engineered PreS1 peptide (AuNP@PEG-PreS1), detect the presence of the SerpinB3 antigen overexpressed on liver tumor cells, a biomarker of the onset of liver cell carcinomatous transformation. A proper engineering of the targeting unit, linked to the nanostructure by a polymer chain, affords a sensitivity and specificity larger than 80%, at subnanomolar concentrations. Taking into account the high sensitivity of SERRS and that SB3 overexpression is an early event in liver cell carcinomatous transformation, AuNP@PEG-PreS1 nanostructures could be used in routine diagnostic activities, to improve the accuracy of HCC detection in particular in patients with chronic liver diseases.

摘要

早期发现是提高许多致命疾病(如癌症)预后的最有效手段。在这种情况下,表面增强共振拉曼散射(SERRS)技术被提议作为荧光方法在生物标志物检测中的替代方法,因为 SERRS 纳米结构像荧光标记一样明亮,但更稳定,并且可以使用合适的报告分子的窄拉曼“指纹”清晰地检测到。在这里,我们展示了具有生物相容性的 SERRS 活性金纳米结构,用工程化的 PreS1 肽(AuNP@PEG-PreS1)进行功能化,可检测到在肝癌细胞上过表达的 SerpinB3 抗原,这是肝细胞癌变转化的生物标志物。通过聚合物链将靶向单元适当地连接到纳米结构上,可以提供大于 80%的灵敏度和特异性,在亚纳摩尔浓度下。考虑到 SERRS 的高灵敏度,以及 SB3 的过表达是肝细胞癌变转化的早期事件,AuNP@PEG-PreS1 纳米结构可用于常规诊断活动,以提高 HCC 检测的准确性,特别是在慢性肝病患者中。

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