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.
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Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, Stein KD, Alteri R, Jemal A. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin 2016; 66(4): 271–289
Hou J, Li X, Xie KP. Coupled liquid biopsy and bioinformatics for pancreatic cancer early detection and precision prognostication. Mol Cancer 2021; 20(1): 34
Liu C, Yang Y, Wu Y. Recent advances in exosomal protein detection via liquid biopsy biosensors for cancer screening, diagnosis, and prognosis. AAPS J 2018; 20(2): 41
Siravegna G, Marsoni S, Siena S, Bardelli A. Integrating liquid biopsies into the management of cancer. Nat Rev Clin Oncol 2017; 14(9): 531–548
Soda N, Rehm BHA, Sonar P, Nguyen NT, Shiddiky MJA. Advanced liquid biopsy technologies for circulating biomarker detection. J Mater Chem B Mater Biol Med 2019; 7(43): 6670–6704
Zhang L, Gu C, Wen J, Liu G, Liu H, Li L. Recent advances in nanomaterial-based biosensors for the detection of exosomes. Anal Bioanal Chem 2021; 413(1): 83–102
LeBleu VS, Kalluri R. Exosomes as a multicomponent biomarker platform in cancer. Trends Cancer 2020; 6(9): 767–774
Sharma A, Johnson A. Exosome DNA: critical regulator of tumor immunity and a diagnostic biomarker. J Cell Physiol 2020; 235(3): 1921–1932
Skotland T, Sagini K, Sandvig K, Llorente A. An emerging focus on lipids in extracellular vesicles. Adv Drug Deliv Rev 2020; 159: 308–321
Sandfeld-Paulsen B, Aggerholm-Pedersen N, Bæk R, Jakobsen KR, Meldgaard P, Folkersen BH, Rasmussen TR, Varming K, Jørgensen MM, Sorensen BS. Exosomal proteins as prognostic biomarkers in non-small cell lung cancer. Mol Oncol 2016; 10(10): 1595–1602
Colombo M, Raposo G, Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol 2014; 30(1): 255–289
Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science 2020; 367(6478): eaau6977
Maacha S, Bhat AA, Jimenez L, Raza A, Haris M, Uddin S, Grivel JC. Extracellular vesicles-mediated intercellular communication: roles in the tumor microenvironment and anti-cancer drug resistance. Mol Cancer 2019; 18(1): 55
Meldolesi J. Exosomes and ectosomes in intercellular communication. Curr Biol 2018; 28(8): R435–R444
Quek C, Hill AF. The role of extracellular vesicles in neurodegenerative diseases. Biochem Biophys Res Commun 2017; 483(4): 1178–1186
Silva J, Garcia V, Rodriguez M, Compte M, Cisneros E, Veguillas P, Garcia JM, Dominguez G, Campos-Martin Y, Cuevas J, Peña C, Herrera M, Diaz R, Mohammed N, Bonilla F. Analysis of exosome release and its prognostic value in human colorectal cancer. Genes Chromosomes Cancer 2012; 51(4): 409–418
Yu W, Hurley J, Roberts D, Chakrabortty SK, Enderle D, Noerholm M, Breakefield XO, Skog JK. Exosome-based liquid biopsies in cancer: opportunities and challenges. Ann Oncol 2021; 32(4): 466–477
Khodashenas S, Khalili S, Forouzandeh Moghadam M. A cell ELISA based method for exosome detection in diagnostic and therapeutic applications. Biotechnol Lett 2019; 41(4–5): 523–531
Dragovic RA, Collett GP, Hole P, Ferguson DJ, Redman CW, Sargent IL, Tannetta DS. Isolation of syncytiotrophoblast micro-vesicles and exosomes and their characterisation by multicolour flow cytometry and fluorescence nanoparticle tracking analysis. Methods 2015; 87: 64–74
Chia BS, Low YP, Wang Q, Li P, Gao Z. Advances in exosome quantification techniques. Trends Analyt Chem 2017; 86: 93–106
Mastoridis S, Bertolino GM, Whitehouse G, Dazzi F, Sanchez-Fueyo A, Martinez-Llordella M. Multiparametric analysis of circulating exosomes and other small extracellular vesicles by advanced imaging flow cytometry. Front Immunol 2018; 9: 1583
Luo X, An M, Cuneo KC, Lubman DM, Li L. High-performance chemical isotope labeling liquid chromatography mass spectrometry for exosome metabolomics. Anal Chem 2018; 90(14): 8314–8319
Ko J, Carpenter E, Issadore D. Detection and isolation of circulating exosomes and microvesicles for cancer monitoring and diagnostics using micro-/nano-based devices. Analyst (Lond) 2016; 141(2): 450–460
Witwer KW, Buzás EI, Bemis LT, Bora A, Lässer C, Lötvall J, Nolte-’t Hoen EN, Piper MG, Sivaraman S, Skog J, Théry C, Wauben MH, Hochberg F. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J Extracell Vesicles 2013; 2: 20360
Sun Z, Wang L, Wu S, Pan Y, Dong Y, Zhu S, Yang J, Yin Y, Li G. An electrochemical biosensor designed by using Zr-based metal-organic frameworks for the detection of glioblastoma-derived exosomes with practical application. Anal Chem 2020; 92(5): 3819–3826
Wang L, Pan Y, Liu Y, Sun Z, Huang Y, Li J, Yang J, Xiang Y, Li G. Fabrication of an aptamer-coated liposome complex for the detection and profiling of exosomes based on terminal deoxynucleotidyl transferase-mediated signal amplification. ACS Appl Mater Interfaces 2020; 12(1): 322–329
van der Pol E, Coumans F A W, Grootemaat AE, Gardiner C, Sargent IL, Harrison P, Sturk A, van Leeuwen TG, Nieuwland R. Particle size distribution of exosomes and microvesicles determined by transmission electron microscopy, flow cytometry, nanoparticle tracking analysis, and resistive pulse sensing. J Thromb Haemost 2014; 12(7): 1182–1192
Lin S, Yu Z, Chen D, Wang Z, Miao J, Li Q, Zhang D, Song J, Cui D. Progress in microfluidics-based exosome separation and detection technologies for diagnostic applications. Small 2020; 16(9): e1903916
Yoo SM, Lee SY. Optical biosensors for the detection of pathogenic microorganisms. Trends Biotechnol 2016; 34(1): 7–25
Masud MK, Na J, Younus M, Hossain MSA, Bando Y, Shiddiky MJA, Yamauchi Y. Superparamagnetic nanoarchitectures for disease-specific biomarker detection. Chem Soc Rev 2019; 48(24): 5717–5751
Huang Y, Wang L, Sha L, Wang Y, Duan X, Li G. Highly sensitive detection of lipopolysaccharide based on collaborative amplification of dual enzymes. Anal Chim Acta 2020; 1126: 31–37
Geng Y, Peveler WJ, Rotello VM. Array-based “chemical nose” sensing in diagnostics and drug discovery. Angew Chem Int Ed Engl 2019; 58(16): 5190–5200
Wu J, Hu S, Zhang L, Xin J, Sun C, Wang L, Ding K, Wang B. Tumor circulome in the liquid biopsies for cancer diagnosis and prognosis. Theranostics 2020; 10(10): 4544–4556
Guo SC, Tao SC, Dawn H. Microfluidics-based on-a-chip systems for isolating and analysing extracellular vesicles. J Extracell Vesicles 2018; 7(1): 1508271
Cheng N, Du D, Wang X, Liu D, Xu W, Luo Y, Lin Y. Recent advances in biosensors for detecting cancer-derived exosomes. Trends Biotechnol 2019; 37(11): 1236–1254
Wen W, Yan X, Zhu C, Du D, Lin Y. Recent advances in electrochemical immunosensors. Anal Chem 2017; 89(1): 138–156
Ogino S, Nowak JA, Hamada T Jr, Milner DA Jr, Nishihara R. Insights into pathogenic interactions among environment, host, and tumor at the crossroads of molecular pathology and epidemiology. Annu Rev Pathol 2019; 14(1): 83–103
Zhang L, Gu C, Wen J, Liu G, Liu H, Li L. Recent advances in nanomaterial-based biosensors for the detection of exosomes. Anal Bioanal Chem 2021; 413(1): 83–102
Balaj L, Lessard R, Dai L, Cho YJ, Pomeroy SL, Breakefield XO, Skog J. Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. Nat Commun 2011; 2(1): 180
Mathieu M, Martin-Jaular L, Lavieu G, Théry C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol 2019; 21(1): 9–17
Wolf P. The nature and significance of platelet products in human plasma. Br J Haematol 1967; 13(3): 269–288
Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem 1987; 262(19): 9412–9420
Kowal J, Tkach M, Théry C. Biogenesis and secretion of exosomes. Curr Opin Cell Biol 2014; 29: 116–125
Foster BP, Balassa T, Benen TD, Dominovic M, Elmadjian GK, Florova V, Fransolet MD, Kestlerova A, Kmiecik G, Kostadinova IA, Kyvelidou C, Meggyes M, Mincheva MN, Moro L, Pastuschek J, Spoldi V, Wandernoth P, Weber M, Toth B, Markert UR. Extracellular vesicles in blood, milk and body fluids of the female and male urogenital tract and with special regard to reproduction. Crit Rev Clin Lab Sci 2016; 53(6): 379–395
Delorme-Axford E, Donker RB, Mouillet JF, Chu T, Bayer A, Ouyang Y, Wang T, Stolz DB, Sarkar SN, Morelli AE, Sadovsky Y, Coyne CB. Human placental trophoblasts confer viral resistance to recipient cells. Proc Natl Acad Sci USA 2013; 110(29): 12048–12053
Gehrmann U, Näslund TI, Hiltbrunner S, Larssen P, Gabrielsson S. Harnessing the exosome-induced immune response for cancer immunotherapy. Semin Cancer Biol 2014; 28: 58–67
Cheng Y, Schorey JS. Extracellular vesicles deliver Mycobacterium RNA to promote host immunity and bacterial killing. EMBO Rep 2019; 20(3): e46613
de Carvalho JV, de Castro RO, da Silva EZ, Silveira PP, da Silva-Januário ME, Arruda E, Jamur MC, Oliver C, Aguiar RS, daSilva LL. Nef neutralizes the ability of exosomes from CD4+ T cells to act as decoys during HIV-1 infection. PLoS One 2014; 9(11): e113691
Guay C, Regazzi R. Exosomes as new players in metabolic organ cross-talk. Diabetes Obes Metab 2017;19(Suppl 1): 137–146
Zhang Y, Hu YW, Zheng L, Wang Q. Characteristics and roles of exosomes in cardiovascular disease. DNA Cell Biol 2017; 36(3): 202–211
Budnik V, Ruiz-Cañada C, Wendler F. Extracellular vesicles round off communication in the nervous system. Nat Rev Neurosci 2016; 17(3): 160–172
Sundararajan V, Sarkar FH, Ramasamy TS. The multifaceted role of exosomes in cancer progression: diagnostic and therapeutic implications [corrected]. Cell Oncol (Dordr) 2018; 41(3): 223–252
Yang Y, Li CW, Chan LC, Wei Y, Hsu JM, Xia W, Cha JH, Hou J, Hsu JL, Sun L, Hung MC. Exosomal PD-L1 harbors active defense function to suppress T cell killing of breast cancer cells and promote tumor growth. Cell Res 2018; 28(8): 862–864
Fang T, Lv H, Lv G, Li T, Wang C, Han Q, Yu L, Su B, Guo L, Huang S, Cao D, Tang L, Tang S, Wu M, Yang W, Wang H. Tumor-derived exosomal miR-1247-3p induces cancer-associated fibroblast activation to foster lung metastasis of liver cancer. Nat Commun 2018; 9(1): 191
Liu X, Lu Y, Xu Y, Hou S, Huang J, Wang B, Zhao J, Xia S, Fan S, Yu X, Du Y, Hou L, Li Z, Ding Z, An S, Huang B, Li L, Tang J, Ju J, Guan H, Song B. Exosomal transfer of miR-501 confers doxorubicin resistance and tumorigenesis via targeting of BLID in gastric cancer. Cancer Lett 2019; 459: 122–134
Al-Nedawi K, Meehan B, Micallef J, Lhotak V, May L, Guha A, Rak J. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol 2008; 10(5): 619–624
Jakobsen KR, Paulsen BS, Bæk R, Varming K, Sorensen BS, Jørgensen MM. Exosomal proteins as potential diagnostic markers in advanced non-small cell lung carcinoma. J Extracell Vesicles 2015; 4(1): 26659
Melo SA, Luecke LB, Kahlert C, Fernandez AF, Gammon ST, Kaye J, LeBleu VS, Mittendorf EA, Weitz J, Rahbari N, Reissfelder C, Pilarsky C, Fraga MF, Piwnica-Worms D, Kalluri R. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature 2015; 523(7559): 177–182
Yoon JH, Ham IH, Kim O, Ashktorab H, Smoot DT, Nam SW, Lee JY, Hur H, Park WS. Gastrokine 1 protein is a potential theragnostic target for gastric cancer. Gastric Cancer 2018; 21(6): 956–967
Khan S, Bennit HF, Turay D, Perez M, Mirshahidi S, Yuan Y, Wall NR. Early diagnostic value of survivin and its alternative splice variants in breast cancer. BMC Cancer 2014; 14(1): 176
Zhang P, Zhou X, He M, Shang Y, Tetlow AL, Godwin AK, Zeng Y. Ultrasensitive detection of circulating exosomes with a 3D-nanopatterned microfluidic chip. Nat Biomed Eng 2019; 3(6): 438–451
Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O’Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 2008; 105(30): 10513–10518
Sun Z, Shi K, Yang S, Liu J, Zhou Q, Wang G, Song J, Li Z, Zhang Z, Yuan W. Effect of exosomal miRNA on cancer biology and clinical applications. Mol Cancer 2018; 17(1): 147
Li Z, Ma YY, Wang J, Zeng XF, Li R, Kang W, Hao XK. Exosomal microRNA-141 is upregulated in the serum of prostate cancer patients. Onco Targets Ther 2015; 9: 139–148
Zhou CF, Ma J, Huang L, Yi HY, Zhang YM, Wu XG, Yan RM, Liang L, Zhong M, Yu YH, Wu S, Wang W. Cervical squamous cell carcinoma-secreted exosomal miR-221-3p promotes lymphangiogenesis and lymphatic metastasis by targeting VASH1. Oncogene 2019; 38(8): 1256–1268
Wang X, Luo G, Zhang K, Cao J, Huang C, Jiang T, Liu B, Su L, Qiu Z. Hypoxic tumor-derived exosomal miR-301a mediates M2 macrophage polarization via PTEN/PI3Kγ to promote pancreatic cancer metastasis. Cancer Res 2018; 78(16): 4586–4598
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144(5): 646–674
Boriachek K, Umer M, Islam MN, Gopalan V, Lam AK, Nguyen NT, Shiddiky MJA. An amplification-free electrochemical detection of exosomal miRNA-21 in serum samples. Analyst (Lond) 2018; 143(7): 1662–1669
Li Y, Zhang Y, Qiu F, Qiu Z. Proteomic identification of exosomal LRG1: a potential urinary biomarker for detecting NSCLC. Electrophoresis 2011; 32(15): 1976–1983
Kim HK, Jeong H, Choi BH, Quan YH, Rho J, Park JH, Park Y, Choi Y, Han KN, Choi YH, Hong S. Lung cancer exosome specific protein 1 (LESP-1) as a potential factor for diagnosis and treatment of non-small cell lung cancer. J Clin Oncol 2020; 38(15_suppl): e15550
Tian Y, Ma L, Gong M, Su G, Zhu S, Zhang W, Wang S, Li Z, Chen C, Li L, Wu L, Yan X. Protein profiling and sizing of extracellular vesicles from colorectal cancer patients via flow cytometry. ACS Nano 2018; 12(1): 671–680
Khan S, Bennit HF, Turay D, Perez M, Mirshahidi S, Yuan Y, Wall NR. Early diagnostic value of survivin and its alternative splice variants in breast cancer. BMC Cancer 2014; 14(1): 176
Taylor DD, Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol 2008; 110(1): 13–21
Zhou X, Wen W, Shan X, Zhu W, Xu J, Guo R, Cheng W, Wang F, Qi LW, Chen Y, Huang Z, Wang T, Zhu D, Liu P, Shu Y. A six-microRNA panel in plasma was identified as a potential biomarker for lung adenocarcinoma diagnosis. Oncotarget 2017; 8(4): 6513–6525
Miranda-Castro R, Palchetti I, de-Los-Santos-Álvarez N. The translational potential of electrochemical DNA-based liquid biopsy. Front Chem 2020; 8: 143
Díaz-Fernández A, Lorenzo-Gómez R, Miranda-Castro R, de-Los-Santos-Álvarez N, Lobo-Castañón MJ. Electrochemical aptasensors for cancer diagnosis in biological fluids—a review. Anal Chim Acta 2020; 1124: 1–19
Abi A, Mohammadpour Z, Zuo X, Safavi A. Nucleic acid-based electrochemical nanobiosensors. Biosens Bioelectron 2018; 102: 479–489
Yin X, Hou T, Huang B, Yang L, Li F. Aptamer recognition-trigged label-free homogeneous electrochemical strategy for an ultrasensitive cancer-derived exosome assay. Chem Commun (Camb) 2019; 55(91): 13705–13708
Dong H, Chen H, Jiang J, Zhang H, Cai C, Shen Q. Highly sensitive electrochemical detection of tumor exosomes based on aptamer recognition-induced multi-DNA release and cyclic enzymatic amplification. Anal Chem 2018; 90(7): 4507–4513
Zhao L, Sun R, He P, Zhang X. Ultrasensitive detection of exosomes by target-triggered three-dimensional DNA walking machine and exonuclease III-assisted electrochemical ratiometric biosensing. Anal Chem 2019; 91(22): 14773–14779
Wang L, Zeng L, Wang Y, Chen T, Chen W, Chen G, Li C, Chen J. Electrochemical aptasensor based on multidirectional hybridization chain reaction for detection of tumorous exosomes. Sens Actuators B Chem 2021; 332: 129471
An Y, Jin T, Zhu Y, Zhang F, He P. An ultrasensitive electrochemical aptasensor for the determination of tumor exosomes based on click chemistry. Biosens Bioelectron 2019; 142: 111503
Cao Y, Li L, Han B, Wang Y, Dai Y, Zhao J. A catalytic molecule machine-driven biosensing method for amplified electrochemical detection of exosomes. Biosens Bioelectron 2019; 141: 111397
McLean MH, El-Omar EM. Genetics of gastric cancer. Nat Rev Gastroenterol Hepatol 2014; 11(11): 664–674
Huang R, He L, Xia Y, Xu H, Liu C, Xie H, Wang S, Peng L, Liu Y, Liu Y, He N, Li Z. A sensitive aptasensor based on a hemin/G-quadruplex-assisted signal amplification strategy for electrochemical detection of gastric cancer exosomes. Small 2019; 15(19): e1900735
Wang L, Deng Y, Wei J, Huang Y, Wang Z, Li G. Spherical nucleic acids-based cascade signal amplification for highly sensitive detection of exosomes. Biosens Bioelectron 2021; 191: 113465
Maduraiveeran G, Sasidharan M, Ganesan V. Electrochemical sensor and biosensor platforms based on advanced nanomaterials for biological and biomedical applications. Biosens Bioelectron 2018; 103: 113–129
Kreno LE, Leong K, Farha OK, Allendorf M, Van Duyne RP, Hupp JT. Metal-organic framework materials as chemical sensors. Chem Rev 2012; 112(2): 1105–1125
Heck JG, Napp J, Simonato S, Möllmer J, Lange M, Reichardt HM, Staudt R, Alves F, Feldmann C. Multifunctional phosphate-based inorganic-organic hybrid nanoparticles. J Am Chem Soc 2015; 137(23): 7329–7336
Mao J, Ran D, Xie C, Shen Q, Wang S, Lu W. EGFR/EGFRvIII dual-targeting peptide-mediated drug delivery for enhanced glioma therapy. ACS Appl Mater Interfaces 2017; 9(29): 24462–24475
Cheng G, Li W, Ha L, Han X, Hao S, Wan Y, Wang Z, Dong F, Zou X, Mao Y, Zheng SY. Self-assembly of extracellular vesiclelike metal-organic framework nanoparticles for protection and intracellular delivery of biofunctional proteins. J Am Chem Soc 2018; 140(23): 7282–7291
Cao Y, Wang Y, Yu X, Jiang X, Li G, Zhao J. Identification of programmed death ligand-1 positive exosomes in breast cancer based on DNA amplification-responsive metal-organic frameworks. Biosens Bioelectron 2020; 166: 112452
Kandambeth S, Dey K, Banerjee R. Covalent organic frameworks: chemistry beyond the structure. J Am Chem Soc 2019; 141(5): 1807–1822
Wang M, Pan Y, Wu S, Sun Z, Wang L, Yang J, Yin Y, Li G. Detection of colorectal cancer-derived exosomes based on covalent organic frameworks. Biosens Bioelectron 2020; 169: 112638
Farhana FZ, Umer M, Saeed A, Pannu AS, Shahbazi M, Jabur A, Nam HJ, Ostrikov K, Sonar P, Firoz SH, Shiddiky MJA. Isolation and detection of exosomes using Fe2O3 nanoparticles. ACS Appl Nano Mater 2021; 4(2): 1175–1186
Xu L, Shoaie N, Jahanpeyma F, Zhao J, Azimzadeh M, Al Jamal KT. Optical, electrochemical and electrical (nano)biosensors for detection of exosomes: a comprehensive overview. Biosens Bioelectron 2020; 161: 112222
Kholafazad Kordasht H, Hasanzadeh M. Biomedical analysis of exosomes using biosensing methods: recent progress. Anal Methods 2020; 12(22): 2795–2811
Panagopoulou MS, Wark AW, Birch DJS, Gregory CD. Phenotypic analysis of extracellular vesicles: a review on the applications of fluorescence. J Extracell Vesicles 2020; 9(1): 1710020
Wang L, Yang Y, Liu Y, Ning L, Xiang Y, Li G. Bridging exosome and liposome through zirconium-phosphate coordination chemistry: a new method for exosome detection. Chem Commun (Camb) 2019; 55(18): 2708–2711
Yu X, He L, Pentok M, Yang H, Yang Y, Li Z, He N, Deng Y, Li S, Liu T, Chen X, Luo H. An aptamer-based new method for competitive fluorescence detection of exosomes. Nanoscale 2019; 11(33): 15589–15595
Pan Y, Wang L, Deng Y, Wang M, Peng Y, Yang J, Li G. A simple and sensitive method for exosome detection based on steric hindrance-controlled signal amplification. Chem Commun (Camb) 2020; 56(89): 13768–13771
Tian W, Li P, He W, Liu C, Li Z. Rolling circle extension-actuated loop-mediated isothermal amplification (RCA-LAMP) for ultrasensitive detection of microRNAs. Biosens Bioelectron 2019; 128: 17–22
Huang L, Wang DB, Singh N, Yang F, Gu N, Zhang XE. A dual-signal amplification platform for sensitive fluorescence biosensing of leukemia-derived exosomes. Nanoscale 2018; 10(43): 20289–20295
Huang R, He L, Li S, Liu H, Jin L, Chen Z, Zhao Y, Li Z, Deng Y, He N. A simple fluorescence aptasensor for gastric cancer exosome detection based on branched rolling circle amplification. Nanoscale 2020; 12(4): 2445–2451
Zhang J, Shi J, Liu W, Zhang K, Zhao H, Zhang H, Zhang Z. A simple, specific and “on-off” type MUC1 fluorescence aptasensor based on exosomes for detection of breast cancer. Sens Actuators B Chem 2018; 276: 552–559
Li P, Yu X, Han W, Kong Y, Bao W, Zhang J, Zhang W, Gu Y. Ultrasensitive and reversible nanoplatform of urinary exosomes for prostate cancer diagnosis. ACS Sens 2019; 4(5): 1433–1441
Yu Y, Zhang WS, Guo Y, Peng H, Zhu M, Miao D, Su G. Engineering of exosome-triggered enzyme-powered DNA motors for highly sensitive fluorescence detection of tumor-derived exosomes. Biosens Bioelectron 2020; 167: 112482
Li B, Liu C, Pan W, Shen J, Guo J, Luo T, Feng J, Situ B, An T, Zhang Y, Zheng L. Facile fluorescent aptasensor using aggregation-induced emission luminogens for exosomal proteins profiling towards liquid biopsy. Biosens Bioelectron 2020; 168: 112520
Zhang Z, Tang C, Zhao L, Xu L, Zhou W, Dong Z, Yang Y, Xie Q, Fang X. Aptamer-based fluorescence polarization assay for separation-free exosome quantification. Nanoscale 2019; 11(20): 10106–10113
Liang X, Han L. White peroxidase-mimicking nanozymes: colorimetric pesticide assay without interferences of O2 and color. Adv Funct Mater 2020; 30(28): 2001933
Xu L, Chopdat R, Li D, Al-Jamal KT. Development of a simple, sensitive and selective colorimetric aptasensor for the detection of cancer-derived exosomes. Biosens Bioelectron 2020; 169: 112576
Mokhtarzadeh A, Ezzati Nazhad Dolatabadi J, Abnous K, de la Guardia M, Ramezani M. Nanomaterial-based cocaine aptasensors. Biosens Bioelectron 2015; 68: 95–106
Liu W, Li J, Wu Y, Xing S, Lai Y, Zhang G. Target-induced proximity ligation triggers recombinase polymerase amplification and transcription-mediated amplification to detect tumor-derived exosomes in nasopharyngeal carcinoma with high sensitivity. Biosens Bioelectron 2018; 102: 204–210
Li J, Baird MA, Davis MA, Tai W, Zweifel LS, Adams Waldorf KM, Gale M Jr, Rajagopal L, Pierce RH, Gao X. Dramatic enhancement of the detection limits of bioassays via ultrafast deposition of polydopamine. Nat Biomed Eng 2017; 1: 0082
Lee H, Rho J, Messersmith PB. Facile conjugation of biomolecules onto surfaces via mussel adhesive protein inspired coatings. Adv Mater 2009; 21(4): 431–434
Chen Z, Cheng SB, Cao P, Qiu QF, Chen Y, Xie M, Xu Y, Huang WH. Detection of exosomes by ZnO nanowires coated three-dimensional scaffold chip device. Biosens Bioelectron 2018; 122: 211–216
He F, Liu H, Guo X, Yin BC, Ye BC. Direct exosome quantification via bivalent-cholesterol-labeled DNA anchor for signal amplification. Anal Chem 2017; 89(23): 12968–12975
Zhang Y, Wang D, Yue S, Lu Y, Yang C, Fang J, Xu Z. Sensitive multicolor visual detection of exosomes via dual signal amplification strategy of enzyme-catalyzed metallization of Au nanorods and hybridization chain reaction. ACS Sens 2019; 4(12): 3210–3218
Zhang Y, Jiao J, Wei Y, Wang D, Yang C, Xu Z. Plasmonic colorimetric biosensor for sensitive exosome detection via enzyme-induced etching of gold nanobipyramid@MnO2 nanosheet nanos-tructures. Anal Chem 2020; 92(22): 15244–15252
Munir S, Shah AA, Rahman H, Bilal M, Rajoka MSR, Khan AA, Khurshid M. Nanozymes for medical biotechnology and its potential applications in biosensing and nanotherapeutics. Biotechnol Lett 2020; 42(3): 357–373
Chen J, Xu Y, Lu Y, Xing W. Isolation and visible detection of tumor-derived exosomes from plasma. Anal Chem 2018; 90(24): 14207–14215
Boriachek K, Masud MK, Palma C, Phan HP, Yamauchi Y, Hossain MSA, Nguyen NT, Salomon C, Shiddiky MJA. Avoiding pre-isolation step in exosome analysis: direct isolation and sensitive detection of exosomes using gold-loaded nanoporous ferric oxide nanozymes. Anal Chem 2019; 91(6): 3827–3834
Wang YM, Liu JW, Adkins GB, Shen W, Trinh MP, Duan LY, Jiang JH, Zhong W. Enhancement of the intrinsic peroxidase-like activity of graphitic carbon nitride nanosheets by ssDNAs and its application for detection of exosomes. Anal Chem 2017; 89(22): 12327–12333
Xia Y, Liu M, Wang L, Yan A, He W, Chen M, Lan J, Xu J, Guan L, Chen J. A visible and colorimetric aptasensor based on DNA-capped single-walled carbon nanotubes for detection of exosomes. Biosens Bioelectron 2017; 92: 8–15
Zhou Y, Xu H, Wang H, Ye BC. Detection of breast cancer-derived exosomes using the horseradish peroxidase-mimicking DNAzyme as an aptasensor. Analyst (Lond) 2020; 145: 107–114
Masson JF. Surface plasmon resonance clinical biosensors for medical diagnostics. ACS Sens 2017; 2(1): 16–30
Singh P, Biosensors SPR. Historical perspectives and current challenges. Sens Actuators B Chem 2016; 229: 110–130
Kabashin AV, Evans P, Pastkovsky S, Hendren W, Wurtz GA, Atkinson R, Pollard R, Podolskiy VA, Zayats AV. Plasmonic nanorod metamaterials for biosensing. Nat Mater 2009; 8(11): 867–871
Wang Q, Zou L, Yang X, Liu X, Nie W, Zheng Y, Cheng Q, Wang K. Direct quantification of cancerous exosomes via surface plasmon resonance with dual gold nanoparticle-assisted signal amplification. Biosens Bioelectron 2019; 135: 129–136
Thakur A, Qiu G, Ng SP, Guan J, Yue J, Lee Y, Wu CL. Direct detection of two different tumor-derived extracellular vesicles by SAM-AuNIs LSPR biosensor. Biosens Bioelectron 2017; 94: 400–407
Qiu G, Thakur A, Xu C, Ng SP, Lee Y, Wu CML. Detection of glioma-derived exosomes with the biotinylated antibody-functionalized titanium nitride plasmonic biosensor. Adv Funct Mater 2019; 29(9): 1806761
Im H, Shao H, Park YI, Peterson VM, Castro CM, Weissleder R, Lee H. Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor. Nat Biotechnol 2014; 32(5): 490–495
Zong S, Wang Z, Chen H, Cui Y. Ultrasensitive telomerase activity detection by telomeric elongation controlled surface enhanced Raman scattering. Small 2013; 9(24): 4215–4220
Cialla-May D, Zheng XS, Weber K, Popp J. Recent progress in surface-enhanced Raman spectroscopy for biological and biomedical applications: from cells to clinics. Chem Soc Rev 2017; 46(13): 3945–3961
Wang Z, Zong S, Wang Y, Li N, Li L, Lu J, Wang Z, Chen B, Cui Y. Screening and multiple detection of cancer exosomes using an SERS-based method. Nanoscale 2018; 10(19): 9053–9062
Zong S, Wang L, Chen C, Lu J, Zhu D, Zhang Y, Wang Z, Cui Y. Facile detection of tumor-derived exosomes using magnetic nanobeads and SERS nanoprobes. Anal Methods 2016; 8(25): 5001–5008
Kwizera EA, O’Connor R, Vinduska V, Williams M, Butch ER, Snyder SE, Chen X, Huang X. Molecular detection and analysis of exosomes using surface-enhanced Raman scattering gold nanorods and a miniaturized device. Theranostics 2018; 8(10): 2722–2738
Ma D, Huang C, Zheng J, Tang J, Li J, Yang J, Yang R. Quantitative detection of exosomal microRNA extracted from human blood based on surface-enhanced Raman scattering. Biosens Bioelectron 2018; 101: 167–173
Lee JU, Kim WH, Lee HS, Park KH, Sim SJ. Quantitative and specific detection of exosomal miRNAs for accurate diagnosis of breast cancer using a surface-enhanced Raman scattering sensor based on plasmonic head-flocked gold nanopillars. Small 2019; 15(17): e1804968
Sackmann EK, Fulton AL, Beebe DJ. The present and future role of microfluidics in biomedical research. Nature 2014; 507(7491): 181–189
Chen W, Shao F, Xianyu Y. Microfluidics-implemented biochemical assays: from the perspective of readout. Small 2020; 16(9): e1903388
Kanwar SS, Dunlay CJ, Simeone DM, Nagrath S. Microfluidic device (ExoChip) for on-chip isolation, quantification and characterization of circulating exosomes. Lab Chip 2014; 14(11): 1891–1900
Zhang P, He M, Zeng Y. Ultrasensitive microfluidic analysis of circulating exosomes using a nanostructured graphene oxide/polydopamine coating. Lab Chip 2016; 16(16): 3033–3042
Vaidyanathan R, Naghibosadat M, Rauf S, Korbie D, Carrascosa LG, Shiddiky MJA, Trau M. Detecting exosomes specifically: a multiplexed device based on alternating current electrohydrodynamic induced nanoshearing. Anal Chem 2014; 86(22): 11125–11132
Woo HK, Sunkara V, Park J, Kim TH, Han JR, Kim CJ, Choi HI, Kim YK, Cho YK. Exodisc for rapid, size-selective, and efficient isolation and analysis of nanoscale extracellular vesicles from biological samples. ACS Nano 2017; 11(2): 1360–1370
Liang LG, Kong MQ, Zhou S, Sheng YF, Wang P, Yu T, Inci F, Kuo WP, Li LJ, Demirci U, Wang S. An integrated doublefiltration microfluidic device for isolation, enrichment and quantification of urinary extracellular vesicles for detection of bladder cancer. Sci Rep 2017; 7(1): 46224
Zhu L, Wang K, Cui J, Liu H, Bu X, Ma H, Wang W, Gong H, Lausted C, Hood L, Yang G, Hu Z. Label-free quantitative detection of tumor-derived exosomes through surface plasmon resonance imaging. Anal Chem 2014; 86(17): 8857–8864
Shao H, Chung J, Balaj L, Charest A, Bigner DD, Carter BS, Hochberg FH, Breakefield XO, Weissleder R, Lee H. Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy. Nat Med 2012; 18(12): 1835–1840
Shin SR, Kilic T, Zhang YS, Avci H, Hu N, Kim D, Branco C, Aleman J, Massa S, Silvestri A, Kang J, Desalvo A, Hussaini MA, Chae SK, Polini A, Bhise N, Hussain MA, Lee H, Dokmeci MR, Khademhosseini A. Label-free and regenerative electrochemical microfluidic biosensors for continual monitoring of cell secretomes. Adv Sci (Weinh) 2017; 4(5): 1600522
Hamada T, Keum N, Nishihara R, Ogino S. Molecular pathological epidemiology: new developing frontiers of big data science to study etiologies and pathogenesis. J Gastroenterol 2017; 52(3): 265–275
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This work was supported by the National Natural Science Foundation of China (No. 81772593).
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Ying Deng, Zhaowei Sun, Lei Wang, Minghui Wang, Jie Yang, and Genxi Li declare that they have no conflict of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.
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Deng, Y., Sun, Z., Wang, L. et al. Biosensor-based assay of exosome biomarker for early diagnosis of cancer. Front. Med. 16, 157–175 (2022). https://doi.org/10.1007/s11684-021-0884-z
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DOI: https://doi.org/10.1007/s11684-021-0884-z