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基于双重肿瘤外泌体生物标志物协同识别的纳升级液体活检用于胰腺癌的精准早期诊断。

Dual Tumor Exosome Biomarker Co-recognitions Based Nanoliquid Biopsy for the Accurate Early Diagnosis of Pancreatic Cancer.

机构信息

Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Medical Sciences (2021RU012), Shanghai 200050, People's Republic of China.

Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.

出版信息

ACS Nano. 2023 Jun 27;17(12):11384-11395. doi: 10.1021/acsnano.3c00674. Epub 2023 Jun 8.

Abstract

Pancreatic cancer, with extremely limited treatment options and poor prognosis, urgently needs a breakthrough in early diagnosis and monitoring. Tumor exosomes (T-Exos) detection is presently one of the most clinically significant liquid biopsy approaches for non-invasive pancreatic cancer early diagnosis, which, unfortunately, cannot be applied as a routine diagnostic tool until a number of obstacles, such as unsatisfactory specificity and sensitivity, as well as labor-intensive purification and analysis procedures by ultracentrifugation and enzyme-linked immunosorbent assay, are overcome. Here, we report a facile nanoliquid biopsy assay for the especially specific, ultrasensitive yet economical T-Exos detection by a dual specific biomarker antigen co-recognition and capturing strategy, which is enabled by grafting two corresponding capture antibodies on magnetic nanoparticles and gold nanoparticles, for the accurate detection of target tumor exosomes. This approach exhibits excellent specificity and ultrahigh sensitivity of detecting as low as 78 pg/mL pancreatic cancer exosome specific protein GPC1. Successful screening of 21 pancreatic cancer samples from 22 normal control cases with the enhanced specificity and sensitivity ensures the promising non-invasive monitoring and diagnosis for early stage pancreatic cancer.

摘要

胰腺癌的治疗选择极其有限,预后较差,因此迫切需要在早期诊断和监测方面取得突破。肿瘤外泌体(T-Exos)检测是目前最具临床意义的非侵入性胰腺癌早期诊断液体活检方法之一,但由于特异性和灵敏度不理想,以及通过超速离心和酶联免疫吸附试验进行的纯化和分析过程繁琐等诸多障碍,该方法尚未成为常规诊断工具。在这里,我们报告了一种简便的纳米液体活检分析方法,通过双特异性生物标志物抗原共同识别和捕获策略,实现了特别特异、超高灵敏度且经济的 T-Exos 检测,该策略通过在磁性纳米颗粒和金纳米颗粒上嫁接两种相应的捕获抗体来实现,用于准确检测靶肿瘤外泌体。该方法在检测低至 78 pg/mL 胰腺癌外泌体特异性蛋白 GPC1 时表现出优异的特异性和超高灵敏度。对 22 例正常对照病例中的 21 例胰腺癌样本进行的成功筛选,提高了特异性和灵敏度,确保了对早期胰腺癌的有前途的非侵入性监测和诊断。

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