Department of Biomedical Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260, USA.
Exp Biol Med (Maywood). 2022 Dec;247(23):2152-2172. doi: 10.1177/15353702221110813. Epub 2022 Aug 6.
Cancer liquid biopsy detects circulating biomarkers in body fluids, provides information that complements medical imaging and tissue biopsy, allows sequential monitoring of cancer development, and, therefore, has shown great promise in cancer screening, diagnosis, and prognosis. Exosomes (also known as small extracellular vesicles) are cell-secreted, nanosized vesicles that transport biomolecules such as proteins and RNAs for intercellular communication. Exosomes are actively involved in cancer development and progression and have become promising circulating biomarkers for cancer liquid biopsy. Conventional exosome characterization methods such as quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) are limited by low sensitivity, tedious process, large sample volume, and high cost. To overcome these challenges, new biosensors have been developed to offer sensitive, simple, fast, high throughput, low sample consumption, and cost-effective detection of exosomal biomarkers. In this review, we summarized recent advances in nanotechnology-enabled biosensors that detect exosomal RNAs (both microRNAs and mRNAs) and proteins for cancer screening, diagnosis, and prognosis. The biosensors were grouped based on their sensing mechanisms, including fluorescence-based biosensors, colorimetric biosensors, electrical/electrochemical biosensors, plasmonics-based biosensors, surface-enhanced Raman spectroscopy (SERS)-based biosensors, and inductively coupled plasma mass spectrometry (ICP-MS) and photothermal biosensors. The future directions for the development of exosome-based biosensors were discussed.
癌症液体活检可检测体液中的循环生物标志物，提供与医学成像和组织活检互补的信息，可用于连续监测癌症的发展，因此在癌症筛查、诊断和预后方面显示出巨大的潜力。外泌体（也称为小细胞外囊泡）是细胞分泌的纳米级囊泡，可转运蛋白质和 RNA 等生物分子，从而实现细胞间通讯。外泌体积极参与癌症的发生和发展，已成为癌症液体活检有前途的循环生物标志物。传统的外泌体表征方法，如实时定量聚合酶链反应（qRT-PCR）和酶联免疫吸附测定（ELISA），受到灵敏度低、过程繁琐、样本量大和成本高的限制。为了克服这些挑战，已经开发出新型生物传感器来灵敏、简单、快速、高通量、低样本消耗且具有成本效益地检测外泌体生物标志物。在本综述中，我们总结了基于纳米技术的生物传感器在检测癌症筛查、诊断和预后中外泌体 RNA（miRNA 和 mRNA）和蛋白质方面的最新进展。根据它们的传感机制，生物传感器可分为基于荧光的生物传感器、比色生物传感器、电学/电化学生物传感器、等离子体生物传感器、基于表面增强拉曼光谱（SERS）的生物传感器和电感耦合等离子体质谱（ICP-MS）和光热生物传感器。讨论了基于外泌体的生物传感器的未来发展方向。
