基于功能化水凝胶的肿瘤源性外泌体高灵敏检测  

Functionalized Hydrogel for Highly Sensitive Detection of Tumor-Derived Exosomes

作　　者：杨朝雁 赵书瑾 王子烨 刘娇[1] 宗慎飞[2] 王著元[2] 李炳祥 崔一平[2] Yang Zhaoyan;Zhao Shujin;Wang Ziye;Liu Jiao;Zong Shenfei;Wang Zhuyuan;Li Bingxiang;Cui Yiping(College of Electronic and Optical Engineering&College of Flexible Electronics(Future Technology),Nanjing University of Posts and Telecommunications,Nanjing 210023,Jiangsu,China;School of Electronic Science and Engineering,Southeast University,Nanjing 210096,Jiangsu,China)

机构地区：[1]南京邮电大学电子与光学工程学院,柔性电子(未来技术)学院,江苏南京210023 [2]东南大学电子科学与工程学院,江苏南京210096

出　　处：《光学学报》2023年第21期237-245,共9页Acta Optica Sinica

基　　金：国家重点研发计划(2022YFA1405000);国家自然科学基金(RK106LH21001,62175030,62175027);江苏省自然科学基金重大项目(BK20212004);南京邮电大学人才招聘自然科学研究启动基金(NY222105,NY222122,NY222080,NY222121)。

摘　　要：提出一种外泌体检测新方法,通过将表面增强拉曼散射(SERS)纳米探针固定在核酸适体(DNA)功能化水凝胶中,实现对肿瘤源性外泌体的高灵敏度光学检测。SERS纳米探针被用于识别肿瘤源性外泌体并产生指纹光学信号。SERS活性DNA功能化水凝胶(简称“SD水凝胶”)作为传感器,不仅提供了用于生物识别的三维反应位点,而且可放大SERS纳米探针的光学信号。选择性地与靶外泌体结合后,SERS纳米探针脱离SD水凝胶,导致SERS信号减弱,从而实现光学检测。通过SERS信号变化,SD水凝胶可以定量、灵敏地检测肿瘤源性外泌体,浓度检测限(LOD)约为22μL^(-1)。该SD水凝胶将为临床癌症诊断提供一种新的技术手段。Objective Exosomes play a vital role in intracellular communications and the exchange of substances.Compared with normal cells,tumor cells secrete more exosomes with tumor-specific proteins,which makes tumor-derived exosomes an important kind of cancer biomarker.Thus,the detection of tumor-derived exosomes can provide critical information for the diagnosis of cancer.However,the current detection methods for tumor-derived exosomes still have some shortcomings,including tedious operation and limited accuracy.It is necessary to develop a method with convenient operation and high sensitivity to detect exosomes.Surface-enhanced Raman spectroscopy(SERS)has been widely applied in the biological detection fields due to its excellent optical properties.SERS-based exosome detection methods have flourished in recent years.Many materials have been combined with SERS probes to achieve optimal detection results.Hydrogels are waterswellable polymeric materials with a three-dimensional(3D)network structure synthesized by crosslinking hydrophilic polymers.The porous structure of hydrogels is similar to that of the extracellular matrix.Specifically,acrydite-modified DNA can be easily incorporated into hydrogels during gel formation to recognize and immobilize biomolecules.More importantly,biomolecules can retain their intrinsic structure and function in hydrogels.Therefore,we wish to realize highly efficient and sensitive detection of tumor-derived exosomes by combining the SERS probe with hydrogels.Methods We demonstrate an optical detection of tumor-derived exosomes by developing SERS-active DNA functionalized hydrogels(denoted as SD hydrogels).The details of detection are presented in Fig.1.SD hydrogels consist of two parts.One is SERS nanoprobes for the recognition of exosomes and the generation of SERS signals[Fig.1(a)],and the other is DNA-functionalized polyacrylamide hydrogels(denoted as DPAAm hydrogels)for the immobilization of SERS nanoprobes and the amplification of Raman signals.These two parts are connected by the DNA

关 键 词：生物光学 表面增强拉曼散射光谱技术 光学检测 外泌体 纳米探针 水凝胶 

分 类 号：O433[机械工程—光学工程]