Wang Minghui, Pan Yanhong, Wu Shuai, Sun Zhaowei, Wang Lei, Yang Jie, Yin Yongmei, Li Genxi
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, PR China.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, PR China.
Biosens Bioelectron. 2020 Dec 1;169:112638. doi: 10.1016/j.bios.2020.112638. Epub 2020 Sep 21.
Covalent organic frameworks (COFs) have attracted more and more attention due to their diverse structures and multifunctionality. Their unique physicochemical properties make them exhibit great application potential in the field of biosensing. In this work, we have designed and fabricated a novel COFs-based nanoprobe named HRP-pSC-AuNPs@COFs, where spherical COFs are functionalized with para-sulfocalix [4] arene hydrate (pSC)-modified gold nanoparticles (AuNPs) and horseradish peroxidase (HRP). Then, we have applied it for the electrochemical detection of colorectal cancer (CRC)-derived exosomes. In this design, pSC as amicable linker can recognize and bind with various amino acid residues on the exosomes surface, while AuNPs with excellent conductivity can accelerate the migration of charge carriers and improve the response of biosensors. Noteworthy, the high porosity of COFs allows them to load a large amount of HRP, endowing COF with high catalytic activity. Meanwhile, the exoskeleton of COFs can maintain the functionality of HRP with significantly elevated stability. With such design, the proposed method shows excellent analytical performance for the detection of CRC-derived exosomes in the linear range from 5 × 10 to 10 particles/μL with a detection limit down to 160 particles/μL. Further, this method has also been used to analyze clinical serum sample, and can successfully distinguish CRC patients from healthy people, indicating the promising potential in clinical diagnosis.
共价有机框架（COFs）因其多样的结构和多功能性而受到越来越多的关注。其独特的物理化学性质使其在生物传感领域展现出巨大的应用潜力。在这项工作中，我们设计并制备了一种新型的基于COFs的纳米探针，名为HRP-pSC-AuNPs@COFs，其中球形COFs用对磺基杯[4]芳烃水合物（pSC）修饰的金纳米颗粒（AuNPs）和辣根过氧化物酶（HRP）进行了功能化。然后，我们将其应用于电化学检测结直肠癌（CRC）衍生的外泌体。在这种设计中，pSC作为友好的连接体可以识别并结合外泌体表面的各种氨基酸残基，而具有优异导电性的AuNPs可以加速电荷载流子的迁移并改善生物传感器的响应。值得注意的是，COFs的高孔隙率使其能够负载大量的HRP，赋予COF高催化活性。同时，COFs的外骨架可以显著提高稳定性并维持HRP的功能。通过这种设计，所提出的方法在5×10至10颗粒/μL的线性范围内对CRC衍生外泌体的检测表现出优异的分析性能，检测限低至160颗粒/μL。此外，该方法还被用于分析临床血清样本，并且能够成功地区分CRC患者和健康人，表明其在临床诊断中具有广阔的应用前景。
