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Progress in Chemistry 2022, Vol. 34 Issue (1): 178-197 DOI: 10.7536/PC210346 Previous Articles   Next Articles

• Review •

Nanotechnology for Detection of Circulating Tumor Cells and Extracellular Vesicles

Jiali Wang1, Ling Zhu2, Chen Wang2(), Shengbin Lei1(), Yanlian Yang2()   

  1. 1 Tianjin University,Tianjin 300350, China
    2 CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China
  • Received: Revised: Online: Published:
  • Contact: Chen Wang, Shengbin Lei, Yanlian Yang
  • Supported by:
    Strategic Priority Research Program of the Chinese Academy of Sciences(XDB36000000); Key R&D Project(2017YFA0205000); National Natural Science Foundation of China(51861135103); National Natural Science Foundation of China(31971295); National Natural Science Foundation of China(21773042); Key Frontier Science Research Project(QYZDJ-SSW-SLH048); Youth Innovation Promotion Association of Chinese Academy of Sciences(2018048)
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Tumor liquid biopsy achieves accurate diagnosis of disease by detecting biomarkers in the body fluids which are of great importance for early diagnosis and dynamic monitoring of malignant tumors and are essential biomarkers for liquid biopsies. Circulating tumor cells (CTC) are tumor cells released into the blood from tumor tissue, and extracellular vesicles (EV) are membrane vesicles secreted by cells. Both of them carry tumor molecular information and are closely related to tumor progression and metastasis. Nanomaterials are widely used to detect CTCs and EVs due to their high specific surface area, unique optical, electrical, magnetic and other physical and chemical characteristics that can improve the detection sensitivity and specificity. Nanomaterial-based detection of CTCs and EVs has provided important information for tumor formation, progression, metastasis, and treatment response, and holds great potential in the clinical application. This article reviewes the progress of nanotechnology in three aspects: specific recognition, efficient capture or isolation, and identification of CTC and EV. It includes the functionalization of recognition probes on the surface of nanomaterials to improve the detection specificity and the latest advances in capture and identification of nanomaterials and nanotechnology. It may provide information for the development of liquid biopsy nanotechnology by discussing the advantages and challenges of liquid biopsy technology based on functionalized nanomaterials.

Contents

1 Introduction

2 Functionalized modification of CTC and EV recognition probes

3 Efficient capture of CTC and EV by nanomaterials

4 Identification and detection of CTC and EV

4.1 Signal amplification technology based on functional nanomaterials

4.2 Signal conversion technology based on functional nanomaterials

5 Integration technology of capture and detection of nanomaterials and microchips

6 POCT

7 Conclusion and prospect

Fig. 1 (a) Biogenesis of extracellular vesicles; (b) Circulating tumor cells and their role in tumor metastasis; (c) Surface enhanced Raman; (d) Microfluidic chip; (e) Nanoparticles trapping; (f) Fluorescence nanotechnology: red represents nanorods, yellow are gold nanoparticles, and green are quantum dots.
Fig. 2 (a)Schematic diagram of HER2-targeted peptide screening and (b)CTC isolation via Pep@MNPs.
Fig. 3 CTC analysis system based on AGNPR and SPION (a, b) and its application in CTC capture, enrichment, detection and release[61]
Fig.4 Flow cytometry analysis of EV extracted by hypercentrifugation from cell culture supernatant or human serum using aldehyde latex microbeads[71]
Fig. 5 Illustration of multivalent aptamer network for capture and electrochemical detection of CTCs in whole blood[85]
Fig. 6 Working principle of the proposed method for extracellular vesicles detection based on a copper(Ⅱ)-mediated signal amplification strategy[99]
[1]
Pantel K, Alix-Panabières C. Trends Mol. Med., 2010,16(9): 398.

doi: 10.1016/j.molmed.2010.07.001 pmid: 20667783
[2]
Pantel K, Alix-Panabières C. Nat. Rev. Clin. Oncol., 2019,16(7): 409.

doi: 10.1038/s41571-019-0187-3 pmid: 30796368
[3]
Eslami-S Z, CortÉs-Hernández L E, Cayrefourcq L, Alix-Panabières C. Cold Spring Harb. Perspect. Med., 2020,10(6): a037333.

doi: 10.1101/cshperspect.a037333
[4]
Gerlinger M, Rowan A, Horswell S, et al. Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing[J]. New England Journal of Medicine, 2012, 366(10):883.

doi: 10.1056/NEJMoa1113205
[5]
Bardelli A, Pantel K. Cancer Cell, 2017,31(2): 172.

doi: S1535-6108(17)30002-8 pmid: 28196593
[6]
Murtaza M, Dawson S J, Pogrebniak K, Rueda O M, Provenzano E, Grant J, Chin S F, Tsui D W Y, Marass F, Gale D, Ali H R, Shah P, Contente-Cuomo T, Farahani H, Shumansky K, Kingsbury Z, Humphray S, Bentley D, Shah S P, Wallis M, Rosenfeld N, Caldas C. Nat. Commun., 2015,6(1): 8760.

doi: 10.1038/ncomms9760
[7]
Keller L, Pantel K. Nat. Rev. Cancer, 2019,19(10): 553.

doi: 10.1038/s41568-019-0180-2 pmid: 31455893
[8]
Zhang W, Xia W J, Lv Z, Ni C, Xin Y, Yang L. Cell. Physiol. Biochem., 2017,41(2): 755.

doi: 10.1159/000458736 pmid: 28214887
[9]
Siravegna G, Marsoni S, Siena S, Bardelli A. Nat. Rev. Clin. Oncol., 2017,14(9): 531.

doi: 10.1038/nrclinonc.2017.14 pmid: 28252003
[10]
Cristofanilli M. Semin. Oncol., 2006,33: 9.

pmid: 16797376
[11]
Nagrath S, Sequist L V, Maheswaran S, Bell D W, Irimia D, Ulkus L, Smith M R, Kwak E L, Digumarthy S, Muzikansky A, Ryan P, Balis U J, Tompkins R G, Haber D A, Toner M. Nature, 2007,450(7173): 1235.

doi: 10.1038/nature06385
[12]
Guo Shan, Zhou Xiang. Porgress in Chemistry, 2021,33(01):1.
( 郭珊, 周翔. 化学进展, 2021,33(01):1. )
[13]
Yáñez-MÓ M, Siljander P R M, Andreu Z, Bedina Zavec A, Borràs F E, Buzas E I, Buzas K, Casal E, Cappello F, Carvalho J, Colás E, Cordeiro-da Silva A, Fais S, Falcon-Perez J M, Ghobrial I M, Giebel B, Gimona M, Graner M, Gursel I, Gursel M, Heegaard N H H, Hendrix A, Kierulf P, Kokubun K, Kosanovic M, Kralj-Iglic V, Krämer-Albers E M, Laitinen S, Lässer C, Lener T, Ligeti E, Linē A, Lipps G, Llorente A, Lötvall J, Man?ek-Keber M, Marcilla A, Mittelbrunn M, Nazarenko I, Nolte-‘t Hoen E N M, Nyman T A, O'Driscoll L, Olivan M, Oliveira C, Pállinger É, del Portillo H A, ReventÓs J, Rigau M, Rohde E, Sammar M, Sánchez-Madrid F, SantarÉm N, Schallmoser K, Stampe Ostenfeld M, Stoorvogel W, Stukelj R, van der Grein S G, Helena Vasconcelos M, Wauben M H M, de Wever O. J. Extracell. Vesicles, 2015,4(1): 27066.

doi: 10.3402/jev.v4.27066
[14]
Thery C, Witwer K W, Aikawa E, Alcaraz M J, Anderson J D, Andriantsitohaina R, Antoniou A, Arab T, Archer F, Atkin-Smith G K, Ayre D C, Bach J M, Bachurski D, Baharvand H, Balaj L, Baldacchino S, Bauer N N, Baxter A A, Bebawy M, Beckham C, Bedina Z A, Benmoussa A, Berardi A C, Bergese P, Bielska E, Blenkiron C, Bobis-Wozowicz S, Boilard E, Boireau W, Bongiovanni A, Borras F E, Bosch S, Boulanger C M, Breakefield X, Breglio A M, Brennan M A, Brigstock D R, Brisson A, Broekman M L, Bromberg J F, Bryl-Gorecka P, Buch S, Buck A H, Burger D, Busatto S, Buschmann D, Bussolati B, Buzas E I, Byrd J B, Camussi G, Carter D R, Caruso S, Chamley L W, Chang Y T, Chen C, Chen S, Cheng L, Chin A R, Clayton A, Clerici S P, Cocks A, Cocucci E, Coffey R J, Cordeiro-Da-Silva A, Couch Y, Coumans F A, Coyle B, Crescitelli R, Criado M F, D'Souza-Schorey C, Das S, Datta C A, de Candia P, De Santana E F, De Wever O, Del P H, Demaret T, Deville S, Devitt A, Dhondt B, Di Vizio D, Dieterich L C, Dolo V, Dominguez R A, Dominici M, Dourado M R, Driedonks T A, Duarte F V, Duncan H M, Eichenberger R M, Ekstrom K, El A S, Elie-Caille C, Erdbrugger U, Falcon-Perez J M, Fatima F, Fish J E, Flores-Bellver M, Forsonits A, Frelet-Barrand A, Fricke F, Fuhrmann G, Gabrielsson S, Gamez-Valero A, Gardiner C, Gartner K, Gaudin R, Gho Y S, Giebel B, Gilbert C, Gimona M, Giusti I, Goberdhan D C, Gorgens A, Gorski S M, Greening D W, Gross J C, Gualerzi A, Gupta G N, Gustafson D, Handberg A, Haraszti R A, Harrison P, Hegyesi H, Hendrix A, Hill A F, Hochberg F H, Hoffmann K F, Holder B, Holthofer H, Hosseinkhani B, Hu G, Huang Y, Huber V, Hunt S, Ibrahim A G, Ikezu T, Inal J M, Isin M, Ivanova A, Jackson H K, Jacobsen S, Jay S M, Jayachandran M, Jenster G, Jiang L, Johnson S M, Jones J C, Jong A, Jovanovic-Talisman T, Jung S, Kalluri R, Kano S I, Kaur S, Kawamura Y, Keller E T, Khamari D, Khomyakova E, Khvorova A, Kierulf P, Kim K P, Kislinger T, Klingeborn M, Klinke D N, Kornek M, Kosanovic M M, Kovacs A F, Kramer-Albers E M, Krasemann S, Krause M, Kurochkin I V, Kusuma G D, Kuypers S, Laitinen S, Langevin S M, Languino L R, Lannigan J, Lasser C, Laurent L C, Lavieu G, Lazaro-Ibanez E, Le Lay S, Lee M S, Lee Y, Lemos D S, Lenassi M, Leszczynska A, Li I T, Liao K, Libregts S F, Ligeti E, Lim R, Lim S K, Line A, Linnemannstons K, Llorente A, Lombard C A, Lorenowicz M J, Lorincz A M, Lotvall J, Lovett J, Lowry M C, Loyer X, Lu Q, Lukomska B, Lunavat T R, Maas S L, Malhi H, Marcilla A, Mariani J, Mariscal J, Martens-Uzunova E S, Martin-Jaular L, Martinez M C, Martins V R, Mathieu M, Mathivanan S, Maugeri M, McGinnis L K, McVey M J, Meckes D J, Meehan K L, Mertens I, Minciacchi V R, Moller A, Moller J M, Morales-Kastresana A, Morhayim J, Mullier F, Muraca M, Musante L, Mussack V, Muth D C, Myburgh K H, Najrana T, Nawaz M, Nazarenko I, Nejsum P, Neri C, Neri T, Nieuwland R, Nimrichter L, Nolan J P, Nolte-'T H E, Noren H N, O'Driscoll L, O'Grady T, O'Loghlen A, Ochiya T, Olivier M, Ortiz A, Ortiz L A, Osteikoetxea X, Ostergaard O, Ostrowski M, Park J, Pegtel D M, Peinado H, Perut F, Pfaffl M W, Phinney D G, Pieters B C, Pink R C, Pisetsky D S, Pogge V S E, Polakovicova I, Poon I K, Powell B H, Prada I, Pulliam L, Quesenberry P, Radeghieri A, Raffai R L, Raimondo S, Rak J, Ramirez M I, Raposo G, Rayyan M S, Regev-Rudzki N, Ricklefs F L, Robbins P D, Roberts D D, Rodrigues S C, Rohde E, Rome S, Rouschop K M, Rughetti A, Russell A E, Saa P, Sahoo S, Salas-Huenuleo E, Sanchez C, Saugstad J A, Saul M J, Schiffelers R M, Schneider R, Schoyen T H, Scott A, Shahaj E, Sharma S, Shatnyeva O, Shekari F, Shelke G V, Shetty A K, Shiba K, Siljander P R, Silva A M, Skowronek A, Snyder O N, Soares R P, Sodar B W, Soekmadji C, Sotillo J, Stahl P D, Stoorvogel W, Stott S L, Strasser E F, Swift S, Tahara H, Tewari M, Timms K, Tiwari S, Tixeira R, Tkach M, Toh W S, Tomasini R, Torrecilhas A C, Tosar J P, Toxavidis V, Urbanelli L, Vader P, van Balkom B W, van der Grein S G, Van Deun J, van Herwijnen M J, Van Keuren-Jensen K, van Niel G, van Royen M E, van Wijnen A J, Vasconcelos M H, Vechetti I J, Veit T D, Vella L J, Velot E, Verweij F J, Vestad B, Vinas J L, Visnovitz T, Vukman K V, Wahlgren J, Watson D C, Wauben M H, Weaver A, Webber J P, Weber V, Wehman A M, Weiss D J, Welsh J A, Wendt S, Wheelock A M, Wiener Z, Witte L, Wolfram J, Xagorari A, Xander P, Xu J, Yan X, Yanez-Mo M, Yin H, Yuana Y, Zappulli V, Zarubova J, Zekas V, Zhang J Y, Zhao Z, Zheng L, Zheutlin A R, Zickler A M, Zimmermann P, Zivkovic A M, Zocco D, Zuba-Surma E K. J. Extracell. Vesicles, 2018,7(1):1535750.

doi: 10.1080/20013078.2018.1535750
[15]
Shao H L, Im H, Castro C M, Breakefield X, Weissleder R, Lee H. Chem. Rev., 2018,118(4): 1917.

doi: 10.1021/acs.chemrev.7b00534
[16]
Kalluri R, Lebleu V S. Science, 2020,367(6478): u6977.
[17]
Möller A, Lobb R J. Nat. Rev. Cancer, 2020,20(12): 697.

doi: 10.1038/s41568-020-00299-w
[18]
Wright M D, Tomlinson M G. Immunol. Today, 1994,15(12): 588.

pmid: 7531445
[19]
Kourembanas S. Annu. Rev. Physiol., 2015,77(1): 13.

doi: 10.1146/physiol.2015.77.issue-1
[20]
Kalluri R. J. Clin. Investig., 2016,126(4): 1208.

doi: 10.1172/JCI81135
[21]
Shao B Y, Xiao Z D. Anal. Chimica Acta, 2020,1114: 74.

doi: 10.1016/j.aca.2020.02.041
[22]
Martín-Gracia B, Martín-Barreiro A, Cuestas-AyllÓn C, Grazú V, Line A, Llorente A, de la Fuente J M, Moros M. J. Mater. Chem. B, 2020,8(31): 6710.

doi: 10.1039/d0tb00861c pmid: 32627783
[23]
Yoon H J, Kozminsky M, Nagrath S. ACS Nano, 2014,8(3): 1995.

doi: 10.1021/nn5004277
[24]
Chen L, Gao X Y, Gao J. Progress in Biochemistry and Biophysics, 2021,48(1):35.
( 陈璐, 高学云, 高靓. 生物化学与生物物理进展, 2021,48(1):35.)
[25]
Pei H M, Li L, Han Z J, Wang Y G, Tang B. Lab a Chip, 2020,20(21): 3854.

doi: 10.1039/D0LC00577K
[26]
Zhang P, Zhou X, He M, Shang Y Q, Tetlow A L, Godwin A K, Zeng Y. Nat. Biomed. Eng., 2019,3(6): 438.

doi: 10.1038/s41551-019-0356-9 pmid: 31123323
[27]
Contreras-Naranjo J C, Wu H J, Ugaz V M. Lab a Chip, 2017,17(21): 3558.

doi: 10.1039/C7LC00592J
[28]
Boriachek K, Islam M N, Möller A, Salomon C, Nguyen N T, Hossain M S A, Yamauchi Y, Shiddiky M J A. Small, 2018,14(6): 1702153.

doi: 10.1002/smll.v14.6
[29]
Montenegro J M, Grazu V, Sukhanova A, Agarwal S, de la Fuente J M, Nabiev I, Greiner A, Parak W J. Adv. Drug Deliv. Rev., 2013,65(5): 677.

doi: 10.1016/j.addr.2012.12.003
[30]
Marques A C, Costa P J, Velho S, Amaral M H. J. Control. Release, 2020,320: 180.

doi: 10.1016/j.jconrel.2020.01.035
[31]
Puertas S, Moros M, Fernández-Pacheco R, Ibarra M R, Grazú V, de la Fuente J M,. J. Phys. D: Appl. Phys., 2010,43(47): 474012.

doi: 10.1088/0022-3727/43/47/474012
[32]
Weissleder R, Haun J B, Devaraj N K, Hilderbrand S A, Lee H. Nature Nanotechnology, 2010,5(9):660.

doi: 10.1038/nnano.2010.148
[33]
Bartczak D, Kanaras A G. Langmuir, 2011,27(16): 10119.

doi: 10.1021/la2022177 pmid: 21728291
[34]
Peng J X, Zhao Q, Zheng W S, Li W Z, Li P, Zhu L, Liu X R, Shao B, Li H P, Wang C, Yang Y L. ACS Appl. Mater. Interfaces, 2017,9(22): 18423.

doi: 10.1021/acsami.7b03905
[35]
Bai L L, Du Y M, Peng J X, Liu Y, Wang Y M, Yang Y L, Wang C. J. Mater. Chem. B, 2014,2(26): 4080.

doi: 10.1039/C4TB00456F
[36]
Esmaeilsabzali H, Beischlag T V, Cox M E, Parameswaran A M, Park E J. Biotechnol. Adv., 2013,31(7): 1063.

doi: 10.1016/j.biotechadv.2013.08.016 pmid: 23999357
[37]
Swennenhuis J F, van Dalum G, Zeune L L, Terstappen L W M M. Expert. Rev. Mol. Diagn., 2016,16(12): 1291.

pmid: 27797592
[38]
Wang L H, Balasubramanian P, Chen A P, Kummar S, Evrard Y A, Kinders R J. Semin. Oncol., 2016,43(4): 464.

doi: 10.1053/j.seminoncol.2016.06.004
[39]
Danila D C, Samoila A, Patel C, Schreiber N, Herkal A, Anand A, Bastos D, Heller G, Fleisher M, Scher H I. Cancer J., 2016,22(5): 315.

doi: 10.1097/PPO.0000000000000220
[40]
Miltenyi S, Müller W, Weichel W, Radbruch A. Cytometry, 1990,11(2): 231.

pmid: 1690625
[41]
Pluim D, Devriese L A, Beijnen J H, Schellens J H M. Cytom. A, 2012,81A(8): 664.

doi: 10.1002/cyto.a.v81a.8
[42]
Giordano A, Gao H, Anfossi S, Cohen E, Mego M, Lee B N, Tin S, de Laurentiis M, Parker C A, Alvarez R H, Valero V, Ueno N T, de Placido S, Mani S A, Esteva F J, Cristofanilli M, Reuben J M. Mol. Cancer Ther., 2012,11(11): 2526.

doi: 10.1158/1535-7163.MCT-12-0460 pmid: 22973057
[43]
Liu X R, Shao B, Peng J X, Li H P, Yang Y L, Kong W Y, Song G H, Jiang H F, Liang X, Yan Y. Breast, 2017,32: 119.

doi: 10.1016/j.breast.2017.01.007
[44]
Yue C Y, Jiang Y B, Li P, Wang Y H, Xue J, Li N N, Li D, Wang R N, Dang Y J, Hu Z Y, Yang Y L, Xu J M. OncoImmunology, 2018,7(7): e1438111.

doi: 10.1080/2162402X.2018.1438111
[45]
Xu J M, Zhang Y, Jia R, Yue C Y, Chang L P, Liu R R, Zhang G R, Zhao C H, Zhang Y Y, Chen C X, Wang Y, Yi X, Hu Z Y, Zou J J, Wang Q R. Clin. Cancer Res., 2019,25(2): 515.

doi: 10.1158/1078-0432.CCR-18-2484
[46]
Liang N X, Liu L, Li P, Xu Y, Hou Y S, Peng J X, Song Y, Bing Z X, Wang Y D, Wang Y Y, Jia Z Q, Yang X Y, Li D, Xu H H, Yu Q, Li S Q, Hu Z Y, Yang Y L. J. Thorac. Dis., 2020,12(8): 4262.

doi: 10.21037/jtd
[47]
Karabacak N M, Spuhler P S, Fachin F, Lim E J, Pai V, Ozkumur E, Martel J M, Kojic N, Smith K, Chen P N, Yang J, Hwang H, Morgan B, Trautwein J, Barber T A, Stott S L, Maheswaran S, Kapur R, Haber D A, Toner M. Nat. Protoc., 2014,9(3): 694.

doi: 10.1038/nprot.2014.044 pmid: 24577360
[48]
Ozkumur E, Shah A M, Ciciliano J C, Emmink B L, Miyamoto D T, Brachtel E, Yu M, Chen P I, Morgan B, Trautwein J, Kimura A, Sengupta S, Stott S L, Karabacak N M, Barber T A, Walsh J R, Smith K, Spuhler P S, Sullivan J P, Lee R J, Ting D T, Luo X, Shaw A T, Bardia A, Sequist L V, Louis D N, Maheswaran S, Kapur R, Haber D A, Toner M. Sci. Transl. Med., 2013,5(179): 179ra47.
[49]
Svobodova Z, Kucerova J, Autebert J, Horak D, Bruckova L, Viovy J L, Bilkova Z. Electrophoresis, 2014,35(2/3): 323.

doi: 10.1002/elps.v35.2-3
[50]
Autebert J, Coudert B, Champ J, Saias L, Guneri E T, Lebofsky R, Bidard F C, Pierga J Y, Farace F, Descroix S, Malaquin L, Viovy J L. Lab a Chip, 2015,15(9): 2090.

doi: 10.1039/C5LC00104H
[51]
Song Y L, Shi Y Z, Huang M J, Wang W, Wang Y, Cheng J, Lei Z C, Zhu Z, Yang C Y. Angew. Chem. Int. Ed., 2019,58(8): 2236.

doi: 10.1002/anie.v58.8
[52]
Glia A, Deliorman M, Sukumar P, Janahi F K, Samara B, Brimmo A T, Qasaimeh M A. Adv. Mater. Technol., 2021,6(6): 2100053.

doi: 10.1002/admt.v6.6
[53]
Cui H J, Wang B S, Wang W S, Hao Y W, Liu C Y, Song K, Zhang S D, Wang S T. ACS Appl. Mater. Interfaces, 2018,10(23): 19545.

doi: 10.1021/acsami.8b06072
[54]
Li Y Y, Lu Q H, Liu H L, Wang J F, Zhang P C, Liang H G, Jiang L, Wang S T. Adv. Mater., 2015,27(43): 6848.

doi: 10.1002/adma.201502615
[55]
Wu C C, Li P, Fan N N, Han J J, Zhang W, Zhang W, Tang B. ACS Appl. Mater. Interfaces, 2019,11(48): 44999.

doi: 10.1021/acsami.9b18410
[56]
Luan C X, Wang H, Han Q, Ma X Y, Zhang D G, Xu Y S, Chen B A, Li M L, Zhao Y J. ACS Appl. Mater. Interfaces, 2018,10(25): 21206.

doi: 10.1021/acsami.8b06882
[57]
Lv S W, Liu Y, Xie M, Wang J, Yan X W, Li Z, Dong W G, Huang W H. ACS Nano, 2016,10(6): 6201.

doi: 10.1021/acsnano.6b02208
[58]
Carney R P, Hazari S, Colquhoun M, Tran D, Hwang B, Mulligan M S, Bryers J D, Girda E, Leiserowitz G S, Smith Z J, Lam K S. Anal. Chem., 2017,89(10): 5357.

doi: 10.1021/acs.analchem.7b00017 pmid: 28345878
[59]
Fan M K, Andrade G F S, Brolo A G. Anal. Chimica Acta, 2020,1097: 1.

doi: 10.1016/j.aca.2019.11.049
[60]
Wu X X, Luo L Q, Yang S, Ma X H, Li Y L, Dong C, Tian Y C, Zhang L G, Shen Z Y, Wu A G. ACS Appl. Mater. Interfaces, 2015,7(18): 9965.

doi: 10.1021/acsami.5b02276
[61]
Ruan H M, Wu X X, Yang C C, Li Z H, Xia Y Z, Xue T, Shen Z Y, Wu A G. ACS Biomater. Sci. Eng., 2018,4(3): 1073.

doi: 10.1021/acsbiomaterials.7b00825
[62]
Xue T, Wang S Q, Ou G Y, Li Y, Ruan H M, Li Z H, Ma Y Y, Zou R F, Qiu J Y, Shen Z Y, Wu A G. Anal. Methods, 2019,11(22): 2918.

doi: 10.1039/C9AY00646J
[63]
Abdulbari H A, Basheer E A M. Chembioeng Rev., 2017,4(2): 92.

doi: 10.1002/cben.v4.2
[64]
Shen C C, Liu S P, Li X Q, Yang M H. Anal. Chem., 2019,91(18): 11614.

doi: 10.1021/acs.analchem.9b01897
[65]
Shen H W, Liu L Y, Yuan Z W, Liu Q, Li B Y, Zhang M, Tang H J, Zhang J, Zhao S Q. Biosens. Bioelectron., 2021,179: 113102.

doi: 10.1016/j.bios.2021.113102
[66]
Shen C L, Zhong L, Xiong L, Liu C, Yu L H, Chu X, Luo X, Zhao M, Liu B Z. Sens. Actuat. B: Chem., 2021,331: 129399.

doi: 10.1016/j.snb.2020.129399
[67]
Rupert D L M, Claudio V, Lässer C, Bally M. Biochim. Et Biophys. Acta BBA Gen. Subj., 2017,1861(1): 3164.
[68]
Melo S A, Luecke L B, Kahlert C, Fernandez A F, Gammon S T, Kaye J, LeBleu V S, Mittendorf E A, Weitz J, Rahbari N, Reissfelder C, Pilarsky C, Fraga M F, Piwnica-Worms D, Kalluri R. Nature, 2015,523(7559): 177.

doi: 10.1038/nature14581
[69]
Li W Z, Shao B, Liu C L, Wang H Y, Zheng W S, Kong W Y, Liu X R, Xu G B, Wang C, Li H P, Zhu L, Yang Y L. Small Methods, 2018,2(11): 1800050.
[70]
Wang H Y, Jiang D Z, Li W Z, Xiang X, Zhao J, Yu B, Wang C, He Z H, Zhu L, Yang Y L. Theranostics, 2019,9(18): 5347.

doi: 10.7150/thno.33114
[71]
Wang H Y, Chen K L, Yang Z J, Li W Z, Wang C, Zhang G J, Zhu L, Liu P N, Yang Y L. Anal. Chem., 2019,91(15): 9580.

doi: 10.1021/acs.analchem.9b00914
[72]
Koliha N, Wiencek Y, Heider U, Jüngst C, Kladt N, Krauthäuser S, Johnston I C D, Bosio A, Schauss A, Wild S. J. Extracell. Vesicles, 2016,5(1): 29975.

doi: 10.3402/jev.v5.29975
[73]
Li T D, Zhang R, Chen H, Huang Z P, Ye X, Wang H, Deng A M, Kong J L. Chem. Sci., 2018,9(24): 5372.

doi: 10.1039/C8SC01611A
[74]
Kwizera E A, O'Connor R, Vinduska V, Williams M, Butch E R, Snyder S E, Chen X, Huang X H. Theranostics, 2018,8(10): 2722.

doi: 10.7150/thno.21358 pmid: 29774071
[75]
Tian Y F, Ning C F, He F, Yin B C, Ye B C. Anal., 2018,143(20): 4915.

doi: 10.1039/C8AN01041B
[76]
Pang Y F, Wang C G, Lu L C, Wang C W, Sun Z W, Xiao R. Biosens. Bioelectron., 2019,130: 204.

doi: 10.1016/j.bios.2019.01.039
[77]
Wang Z L, Zong S F, Wang Y J, Li N, Li L, Lu J, Wang Z Y, Chen B A, Cui Y P. Nanoscale, 2018,10(19): 9053.

doi: 10.1039/C7NR09162A
[78]
Wu T T, Yang Y M, Cao Y, Huang Y, Xu L P, Zhang X J, Wang S T. Sci. China Chem., 2018,61(11): 1423.

doi: 10.1007/s11426-018-9305-6
[79]
Liu W L, Li J P, Wu Y X, Xing S, Lai Y Z, Zhang G. Biosens. Bioelectron., 2018,102: 204.

doi: 10.1016/j.bios.2017.11.033
[80]
Liu C, Zhao J X, Tian F, Cai L L, Zhang W, Feng Q, Chang J Q, Wan F N, Yang Y J, Dai B, Cong Y L, Ding B Q, Sun J S, Tan W H. Nat. Biomed. Eng., 2019,3(3): 183.

doi: 10.1038/s41551-018-0343-6
[81]
Zhang J L, Zhu Y F, Shi J J, Zhang K X, Zhang Z Z, Zhang H L. ACS Appl. Mater. Interfaces, 2020,12(30): 33473.

doi: 10.1021/acsami.0c06785
[82]
Zhang W Z, Chen H, Yang M H, Liao L Q. Mater. Lett., 2020,276: 128219.

doi: 10.1016/j.matlet.2020.128219
[83]
Li J, Lin X F, Zhang Z Y, Tu W W, Dai Z H. Biosens. Bioelectron., 2019,126: 332.

doi: 10.1016/j.bios.2018.09.096
[84]
Liu P F, Wang L, Zhao K R, Liu Z J, Cao H X, Ye S Y, Liang G X. Sens. Actuat. B: Chem., 2020,316: 128131.

doi: 10.1016/j.snb.2020.128131
[85]
Yang J M, Li X L, Jiang B Y, Yuan R, Xiang Y. Anal. Chem., 2020,92(11): 7893.

doi: 10.1021/acs.analchem.0c01195
[86]
Boriachek K, Islam M N, Gopalan V, Lam A K, Nguyen N T, Shiddiky M J A. Anal., 2017,142(12): 2211.

doi: 10.1039/C7AN00672A
[87]
Dong H L, Chen H F, Jiang J Q, Zhang H, Cai C X, Shen Q M. Anal. Chem., 2018,90(7): 4507.

doi: 10.1021/acs.analchem.7b04863
[88]
Chen G Y, Qiu H L, Prasad P N, Chen X Y. Chem. Rev., 2014,114(10): 5161.

doi: 10.1021/cr400425h
[89]
Mendez-Gonzalez D, Lopez-Cabarcos E, Rubio-Retama J, Laurenti M. Adv. Colloid Interface Sci., 2017,249: 66.

doi: 10.1016/j.cis.2017.06.003
[90]
Kikuchi K. Chem. Soc. Rev., 2010,39(6): 2048.

doi: 10.1039/b819316a pmid: 20372693
[91]
Wang Y H, Luo D W, Fang Y, Wu W H, Wang Y J, Xia Y K, Wu F, Li C Y, Lan J M, Chen J H. Sens. Actuat. B: Chem., 2019,298: 126900.

doi: 10.1016/j.snb.2019.126900
[92]
Chen X S, Lan J M, Liu Y X, Li L, Yan L, Xia Y K, Wu F, Li C Y, Li S R, Chen J H. Biosens. Bioelectron., 2018,102: 582.

doi: 10.1016/j.bios.2017.12.012
[93]
Algar W R, Tavares A J, Krull U J. Anal. Chimica Acta, 2010,673(1): 1.

doi: 10.1016/j.aca.2010.05.026
[94]
Chandan H R, Schiffman J D, Balakrishna R G. Sens. Actuat. B: Chem., 2018,258: 1191.

doi: 10.1016/j.snb.2017.11.189
[95]
Zhang P F, Draz M S, Xiong A W, Yan W N, Han H X, Chen W S. J. Nanobiotechnology, 2021,19(1): 116.

doi: 10.1186/s12951-021-00860-1
[96]
Kuo C W, Chueh D Y, Chen P L. J. Nanobiotechnology, 2019,17(1): 26.

doi: 10.1186/s12951-019-0453-7
[97]
Bai Y N, Lu Y X, Wang K, Cheng Z L, Qu Y L, Qiu S H, Zhou L, Wu Z H, Liu H Y, Zhao J L, Mao H J. Nano Micro Lett., 2019,11(1): 1.
[98]
Zhai L Y, Li M X, Pan W L, Chen Y, Li M M, Pang J X, Zheng L, Chen J X, Duan W J. ACS Appl. Mater. Interfaces, 2018,10(46): 39478.

doi: 10.1021/acsami.8b12725
[99]
He F, Wang J, Yin B C, Ye B C. Anal. Chem., 2018,90(13): 8072.

doi: 10.1021/acs.analchem.8b01187
[100]
Gao M L, Yin B C, Ye B C. Anal., 2019,144(20): 5996.

doi: 10.1039/C9AN01328H
[101]
Dutta R, Liba O, Sorelle E D, Winetraub Y, Ramani V C, Jeffrey S S, Sledge G W, de la Zerda A. Nano Lett., 2019,19(4):2334.

doi: 10.1021/acs.nanolett.8b05005
[102]
Xia W X, Li H D, Li Y Q, Li M, Fan J L, Sun W, Li N, Li R J, Shao K, Peng X J. Nano Lett., 2021,21(1): 634.

doi: 10.1021/acs.nanolett.0c04180
[103]
Zeng S W, Baillargeat D, Ho H P, Yong K T. Chem. Soc. Rev., 2014,43(10): 3426.

doi: 10.1039/c3cs60479a
[104]
Parolo C, Merkoçi A. Mater. Today, 2010,13(7/8): 24.
[105]
Wang Q, Zou L Y, Yang X H, Liu X F, Nie W Y, Zheng Y, Cheng Q, Wang K M. Biosens. Bioelectron., 2019,135: 129.

doi: 10.1016/j.bios.2019.04.013
[106]
Im H, Shao H L, Park Y I, Peterson V M, Castro C M, Weissleder R, Lee H. Nat. Biotechnol., 2014,32(5): 490.

doi: 10.1038/nbt.2886
[107]
Liang K, Liu F, Fan J, Sun D L, Liu C, Lyon C J, Bernard D W, Li Y, Yokoi K, Katz M H, Koay E J, Zhao Z, Hu Y. Nat. Biomed. Eng., 2017,1(4): 0021.

doi: 10.1038/s41551-016-0021
[108]
Ahmed M G, Abate M F, Song Y L, Zhu Z, Yan F, Xu Y, Wang X M, Li Q B, Yang C Y. Angew. Chem. Int. Ed., 2017,56(36): 10681.

doi: 10.1002/anie.201702675
[109]
Tang M, Xia H F, Xu C M, Feng J, Ren J G, Miao F, Wu M, Wu L L, Pang D W, Chen G, Zhang Z L. Anal. Chem., 2019,91(23): 15260.

doi: 10.1021/acs.analchem.9b04286 pmid: 31692331
[110]
He M, Crow J, Roth M, Zeng Y, Godwin A K. Lab a Chip, 2014,14(19): 3773.

doi: 10.1039/C4LC00662C
[111]
Zhao Z, Yang Y, Zeng Y, He M. Lab a Chip, 2016,16(3): 489.

doi: 10.1039/C5LC01117E
[112]
Jiang Y, Shi M L, Liu Y, Wan S, Cui C, Zhang L Q, Tan W H. Angew. Chem. Int. Ed., 2017,56(39): 11916.

doi: 10.1002/anie.201703807
[113]
He F, Liu H, Guo X G, Yin B C, Ye B C. Anal. Chem., 2017,89(23): 12968.

doi: 10.1021/acs.analchem.7b03919
[114]
Chen J G, Xu Y C, Lu Y, Xing W L. Anal. Chem., 2018,90(24): 14207.

doi: 10.1021/acs.analchem.8b03031
[115]
Yang J J, Pan B, Zeng F, He B S, Gao Y F, Liu X L, Song Y J. Nano Lett., 2021,21(5): 2001.

doi: 10.1021/acs.nanolett.0c04476
[116]
Jeong S, Park J, Pathania D, Castro C M, Weissleder R, Lee H. ACS Nano, 2016,10(2): 1802.

doi: 10.1021/acsnano.5b07584
[117]
Abate M F, Jia S S, Ahmed M G, Li X R, Lin L, Chen X Q, Zhu Z, Yang C Y. Small, 2019,15(14): 1804890.

doi: 10.1002/smll.v15.14
[118]
Yang J M, Huang X T, Gan C F, Yuan R, Xiang Y. Biosens. Bioelectron., 2019,143: 111604.

doi: 10.1016/j.bios.2019.111604
[119]
Xia N, Wu D H, Yu H Q, Sun W W, Yi X Y, Liu L. Talanta, 2021,221: 121640.

doi: 10.1016/j.talanta.2020.121640
[1] Shan Guo, Xiang Zhou. Detection of Circulating Tumor Cell in Vivo:Technology and Application [J]. Progress in Chemistry, 2021, 33(1): 1-12.
[2] Bin Qiao, Hongfei Chen, Hui Zhang, Chenxin Cai. Analysis and Detection of Tumor Exosomes [J]. Progress in Chemistry, 2019, 31(6): 847-857.
[3] Zhaoxuan Fan, Liang Zhao, Xueji Zhang. The Detection of Circulating Tumor DNA: From Digitalization to Sequencing [J]. Progress in Chemistry, 2019, 31(10): 1384-1395.
[4] Huang Di, Xiang Nan, Tang Wenlai, Zhang Xinjie, Ni Zhonghua. Microfluidics-Based Circulating Tumor Cells Separation [J]. Progress in Chemistry, 2015, 27(7): 882-912.