Biosensor-based assay of exosome biomarker for early diagnosis of cancer

doi:10.1007/s11684-021-0884-z

Front. Med.

2022, Vol. 16

Issue (2) : 157-175 https://doi.org/10.1007/s11684-021-0884-z

REVIEW

Biosensor-based assay of exosome biomarker for early diagnosis of cancer

Ying Deng, Zhaowei Sun, Lei Wang, Minghui Wang, Jie Yang, Genxi Li(

)

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China

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Abstract

Cancer imposes a severe threat to people’s health and lives, thus pressing a huge medical and economic burden on individuals and communities. Therefore, early diagnosis of cancer is indispensable in the timely prevention and effective treatment for patients. Exosome has recently become an attractive cancer biomarker in noninvasive early diagnosis because of the unique physiology and pathology functions, which reflects remarkable information regarding the cancer microenvironment, and plays an important role in the occurrence and evolution of cancer. Meanwhile, biosensors have gained great attention for the detection of exosomes due to their superior properties, such as convenient operation, real-time readout, high sensitivity, and remarkable specificity, suggesting promising biomedical applications in the early diagnosis of cancer. In this review, the latest advances of biosensors regarding the assay of exosomes were summarized, and the superiorities of exosomes as markers for the early diagnosis of cancer were evaluated. Moreover, the recent challenges and further opportunities of developing effective biosensors for the early diagnosis of cancer were discussed.

Keywords biosensor exosome cancer diagnosis

Corresponding Author(s): Genxi Li

About author:

Mingsheng Sun and Mingxiao Yang contributed equally to this work.

Just Accepted Date: 13 August 2021 Online First Date: 27 September 2021 Issue Date: 26 April 2022

Cite this article:

Ying Deng,Zhaowei Sun,Lei Wang, et al. Biosensor-based assay of exosome biomarker for early diagnosis of cancer[J]. Front. Med., 2022, 16(2): 157-175.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-021-0884-z
https://academic.hep.com.cn/fmd/EN/Y2022/V16/I2/157

Tab.1 Exosomal proteins as tumor biomarkers

Tab.2 Exosomal miRNAs as tumor biomarkers

Fig.1 Schematic of representative electrochemistry-based biosensors. (A) Detection of circulating exosomes by using zirconium-based metal-organic frameworks (Zr-MOFs). (a) Fabrication process of Zr-MOFs and Zr-MOFs loaded with methylene blue (MB@Zr-MOFs). (b) Process of electrochemical biosensor for exosome detection using MB@Zr-MOFs. (Reproduced with permission from Ref. [25]. Copyright 2020 American Chemical Society.) (B) Ultrasensitive electrochemical biosensor facilitated with DNA amplification-controlled pH decreases based on pH-responsive MOFs encapsulated with horseradish peroxidase (HRP). (Reproduced with permission from Ref. [92]. Copyright 2020 Elsevier.) (C) Novel nanoprobe-based electrochemical assay for colorectal cancer-derived exosomes. (a) Fabrication process of covalent organic frameworks (COFs)-based nanoprobes. (b) Process of exosomes detection by using HRP-pSC4-AuNPs@COFs nanoprobe. (Reproduced with permission from Ref. [94]. Copyright 2020 Elsevier.)

Tab.3 Electrochemical biosensor for exosome detection

Fig.2 Schematic of representative fluorescence-based biosensors. (A) Fabricating a cationic liposome for signal amplification detection of exosomes. Only in the presence of exosomes, the electrostatic attraction between aptamers and liposome broke down and then the free aptamers could trigger enzyme-mediated DNA extension to form multiple G-quadruplex. (Reproduced with permission from Ref. [26]. Copyright 2019 American Chemical Society.) (B) Simple and sensitive strategy for exosome detection utilizing steric hindrance-to-control signal amplification. (Adapted from Ref. [101], with permission from the Royal Society of Chemistry.) (C) Dual-signal amplification constructed using GNP-DNA-FAM conjugates hybridized with RCA technique (Adapted from Ref. [103], with permission from the Royal Society of Chemistry.) (D) Construction of exosome-triggered enzyme-powered DNA motors for sensitive exosome assay. (Reproduced with permission from Ref. [107]. Copyright 2020 Elsevier.)

Fig.3 Schematic of representative colorimetry-based biosensors. (A) Enzymatic catalysis-based dopamine polymerization and in-situ deposition for the design of colorimetric aptasensor for exosome detection. (a) Capturing target exosomes with latex beads and then using biotin-labeled aptamers to introduce streptavidin-labeled HRP to accelerate the polymerization of dopamine. A distinguishable color change could be seen, which could be strengthened by in-situ deposition of polydopamine around exosome particles. (b) Process of dopamine polymerization and polydopamine deposition on the surface of exosomes. Polydopamine could link to amine, sulfhydryl, and the phenol groups of proteins. (Reproduced with permission from Ref. [111]. Copyright 2020 Elsevier.) (B) Sensitive multicolor visual biosensor using a dual-signal amplification strategy of enzyme-catalyzed metallization of Au nanorods and hybridization chain reaction. (Reproduced with permission from Ref. [118]. Copyright 2019 American Chemical Society.)

Fig.4 Schematic of representative SPR-based biosensors. (A) Determination of cancerous exosomes based on dual AuNP-assisted signal amplification. (Reproduced with permission from Ref. [129]. Copyright 2019 Elsevier.) (B) Detection of glioma cells derived exosomes via biotinylated anti-CD63 antibody functionalized with titanium nitride (TiN). (Reproduced with permission from Ref. [131]. Copyright 2019 Wiley.)

Fig.5 Schematic of representative SERS-based biosensors. (A) Detection of cancer cells secreted exosomes based on Au nanoparticles decorated with a Raman reporter and magnetic beads with Au shell. (Reproduced with permission from Ref. [135]. Copyright 2018 the Royal Society of Chemistry.) (B) Detection of tumor-derived exosomes by using SERS nanoprobes with a core–shell structure and magnetic nanobeads. Diagram of the fabrication of (a) magnetic nanobead and (b) SERS nanoprobe. (c) Sandwich-type immunocomplex structure composed of exosome, magnetic nanobead, and SERS nanoprobe. Images are not to scale. (Reproduced with permission from Ref. [136]. Copyright 2016 the Royal Society of Chemistry.) (C) Detection of exosomal miRNAs based on plasmonic head-flocked gold nanopillars. (a) Fabrication process of plasmonic gold nanopillar SERS substrate. SEM images of (b) prepared plasmonic gold nanopillar SERS substrates and (c) plasmonic head-flocked gold nanopillar SERS substrates after solvent evaporation. (Reproduced with permission from Ref. [139]. Copyright 2019 Wiley.)

Fig.6 Schematic of representative microfluidic-based biosensors. (A) Detection of circulating exosomes by using a nanostructured GO/polydopamine functionalized microfluidic platform. Description of (a) a single-channel PDMS/glass chip containing an array of Y-shaped microposts and (b) channel and microposts coated with GO and polydopamine (PDA) as a nanostructured interface. (c) Procedure for surface functionalization of microfluidic chips. (Reproduced with permission from Ref. [143]. Copyright 2016 the Royal Society of Chemistry.) (B) Colorimetric detection of exosomes by using a tunable alternating current electrohydrodynamic methodology. (Reproduced with permission from Ref. [144]. Copyright 2014 American Chemical Society.) (C) Detection of exosomes from urine by using an integrated double-filtration microfluidic device. (a) Diagram of a double-filtration microfluidic device for isolation and detection of exosomes. (b) Size description of an assembled double-filtration device. (c) Diagram of direct ELISA for on-chip exosome detection. (d) The ELISA result is imaged via a smart phone, and then data analysis is conducted on a laptop. (Reproduced with permission from Ref. [146]. Copyright 2017 Nature Publishing Group.)

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