Platinum Nanoparticle-Based Collision Electrochemistry for Rapid Detection of Breast Cancer MCF-7 Cells

Abstract

Cancer metastasis is the leading cause of death in cancer patients worldwide and one of the major challenges in treating cancer. Circulating tumor cells (CTCs) play a pivotal role in cancer metastasis. However, the content of CTCs in peripheral blood is minimal, so the detection of CTCs in real samples is extremely challenging. Therefore, efficient enrichment and early detection of CTCs are essential to achieve timely diagnosis of diseases. In this work, we constructed an innovative and sensitive single-nanoparticle collision electrochemistry (SNCE) biosensor for the detection of MCF-7 cells (human breast cancer cells) by immunomagnetic separation technique and liposome signal amplification strategy. Liposomes embedded with platinum nanoparticles (Pt NPs) were used as signal probes, and homemade gold ultramicroelectrodes (Au UME) were used as the working electrodes. The effective collision between Pt NPs and UME would produce distinguishable step-type current. MCF-7 cells were accurately quantified according to the relationship between cell concentration and collision frequency (the number of step-type currents generated per unit time), realizing highly sensitive and specific detection of MCF-7 cells. The SNCE biosensor has a linear range of 10 cells·mL^-1 to 10⁵ cells·mL^-1 with a detection limit as low as 5 cells·mL^-1. In addition, the successful detection of MCF-7 cells in complex samples showed that the SNCE biosensors have great potential for patient sample detection.

Keywords

Circulating tumor cells / Single-nanoparticle collision electrochemistry / Immunomagnetic separation / Liposome / Platinum nanoparticles

References

[1] Xu W, Zou G Q, Hou H S, Ji X. Single particle electrochemistry of collision[J]. Small, 2019, 15(32): 1804908.

[2] Chen M, Lu S M, Wang H W, Long Y T. Tracking light-induced fragmentation of single silver nanoparticles by single entity electrochemistry[J]. J. Electrochem., 2022, 28(3): 2108521.

[3] Sun L L, Wang W, Chen H Y. Dynamic nanoparticle‐substrate contacts regulate multi‐peak behavior of single silver nanoparticle collisions[J]. ChemElectroChem, 2018, 5(20): 2995-2999.

[4] Oja S M, Robinson D A, Vitti N J, Edwards M A, Liu Y W, White H S, Zhang B. Observation of multipeak collision behavior during the electro-oxidation of single Ag nanoparticles[J]. J. Am. Chem. Soc., 2017, 139(2): 708-718.

[5] Sun L L, Wang W, Chen H Y. Correlated optical imaging and electrochemical recording for studying single nanoparticle collisions[J]. J. Electrochem., 2019, 25(3): 386-399.

[6] Defnet P A, Zhang B. Collision, adhesion, and oxidation of single Ag nanoparticles on a polysulfide-modified microelectrode[J]. J. Am. Chem. Soc., 2021, 143(39): 16154-16162.

[7] Ding Q D, Sun Z H, Ma W. Probing conformational kinetics of catalase with and without magnetic field by single-entity collision electrochemistry[J]. Sci. Bull., 2023, 68(21): 2564-2573.

[8] Zhou M, Wang D, Mirkin M V. Electrochemical evaluation of the number of Au atoms in polymeric gold thiolates by single particle collisions[J]. Anal. Chem., 2018, 90(14): 8285-8289.

[9] Su T, Guo J, He Z K, Zhao J J, Gao Z D, Song Y Y. Single-nanoparticle-level understanding of oxidase-like activity of au nanoparticles on polymer nanobrush-based proton reservoirs[J]. Anal. Chem., 2023, 95(31): 11807-11814.

[10] Guo J, Pan J, Chang S, Wang X W, Kong N, Yang W R, He J. Monitoring the dynamic process of formation of plasmonic molecular junctions during single nanoparticle collisions[J]. Small, 2018, 14(15): 1704164.

[11] Hafez M E, Ma H, Ma W, Long Y T. Unveiling the intrinsic catalytic activities of single‐gold‐nanoparticle‐based enzyme mimetics[J]. Angew. Chem. Int. Ed., 2019, 131(19): 6393-6398.

[12] Bai Y Y, Yang Y J, Xu Y, Yang X Y, Zhang Z L. Current lifetime of single-nanoparticle electrochemical collision for in situ monitoring nanoparticles agglomeration and aggregation[J]. Anal. Chem., 2023, 95(9): 4429-4434.

[13] Zhang J H, Zhou Y G. Single particle impact electrochemistry: analyses of nanoparticles and biomolecules[J]. J. Electrochem., 2019, 25(3): 374-385.

[14] Wang H, Yang C, Tang H, Li Y X. Stochastic collision electrochemistry from single G-quadruplex/hemin: electrochemical amplification and microRNA sensing[J]. Anal. Chem., 2021, 93(10): 4593-4600.

[15] Dunevall J, Fathali H, Najafinobar N, Lovric J, Wigstrom J, Cans C S, Ewing A G. Characterizing the catecholamine content of single mammalian vesicles by collision-adsorption events at an electrode[J]. J. Am. Chem. Soc., 2015, 137(13): 4344-4346.

[16] Dick J E. Electrochemical detection of single cancer and healthy cell collisions on a microelectrode[J]. Chem. Commun., 2016, 52(72): 10906-10909.

[17] Qiu X, Dai Q S, Tang H R, Li Y X. Multiplex assays of MicroRNAs by using single particle electrochemical collision in a single run[J]. Anal. Chem., 2023, 95(35): 13376-13384.

[18] Peng M H, Zhou Y G. Impact electrochemical analysis of soft bio-particles: A mini review[J]. Electrochem. Commun., 2023, 150: 107490.

[19] Fosdick S E, Anderson M J, Nettleton E G, Crooks R M. Correlated electrochemical and optical tracking of discrete collision events[J]. J. Am. Chem. Soc., 2013, 135(16): 5994-5997.

[20] Dick J E, Hilterbrand A T, Strawsine L M, Bard A J. Enzymatically enhanced collisions on ultramicroelectrodes for specific and rapid detection of individual viruses[J]. PNAS, 2016, 113(23): 6403-6408.

[21] Dick J E, Renault C, Bard A J. Observation of single-protein and DNA macromolecule collisions on ultramicroelectrodes[J]. J. Am. Chem. Soc., 2015, 137(26): 8376-8379.

[22] Deng Z, Elattar R, Maroun F, Renault C. In situ measurement of the size distribution and concentration of insulating particles by electrochemical collision on hemispherical ultramicroelectrodes[J]. Anal. Chem., 2018, 90(21): 12923-12929.

[23] Ho T L T, Hoang N T T, Lee J, Park J H, Kim B K. Determining mean corpuscular volume and red blood cell count using electrochemical collision events[J]. Biosens. Bioelectron., 2018, 110: 155-159.

[24] Alix‐Panabières C, Pantel K. Characterization of single circulating tumor cells[J]. FEBS letters, 2017, 591(15): 2241-2250.

[25] Edd J F, Mishra A, Smith K C, Kapur R, Maheswaran S, Haber D A, Toner M. Isolation of circulating tumor cells[J]. Iscience, 2022, 25(8): 104696.

[26] Shen Z Y, Wu A G, Chen X Y. Current detection technologies for circulating tumor cells[J]. Chem. Soc. Rev., 2017, 46(8): 2038-2056.

[27] Ferreira M M, Ramani V C, Jeffrey S S. Circulating tumor cell technologies[J]. Mol. Oncol., 2016, 10(3): 374-394.

[28] Rawal S, Yang Y P, Cote R, Agarwal A. Identification and quantitation of circulating tumor cells[J]. Annu. Rev. Anal. Chem., 2017, 10: 321-343.

[29] Lawrence R, Watters M, Davies C R, Pantel K, Lu Y J. Circulating tumor cells for early detection of clinically relevant cancer[J]. Nat. Rev. Clin. Oncol., 2023, 20(7): 487-500.

[30] Bankó P, Lee S Y, Nagygyörgy V, Zrínyi M, Chae C H, Cho D H, Telekes A. Technologies for circulating tumor cell separation from whole blood[J]. J. Hematol. Oncol., 2019, 12: 1-20.

[31] Ju S W, Chen C, Zhang J H, Xu L, Zhang X, Li Z Q, Chen Y X, Zhou J C, Ji F Y, Wang L B. Detection of circulating tumor cells: opportunities and challenges[J]. Biomark. Res., 2022, 10(1): 58.

[32] Moon D H, Lindsay D P, Hong S, Wang A Z. Clinical indications for, and the future of, circulating tumor cells[J]. Adv. Drug. Deliver. Rev., 2018, 125: 143-150.

[33] Tretyakova M S, Menyailo M E, Schegoleva A A, Bokova U A, Larionova I V, Denisov E V. Technologies for viable circulating tumor cell isolation[J]. Int. J. Mol. Sci., 2022, 23(24): 15979.

[34] Feng Z X, Wu J Y, Lu Y J, Chan Y T, Zhang C, Wang D, Luo D, Huang Y, Feng Y B, Wang N. Circulating tumor cells in the early detection of human cancers[J]. Int. J. Biol. Sci., 2022, 18(8): 3251-3265.

[35] Song Y, Tian T, Shi Y, Liu W L, Zou Y, Khajvand T, Wang S L, Zhu Z, Yang C Y. Enrichment and single-cell analysis of circulating tumor cells[J]. Chem. Sci., 2017, 8(3): 1736-1751.

[36] Akpe V, Kim T H, Brown C L, Cock I E. Circulating tumor cells: a broad perspective[J]. J. R. Soc. Interface, 2020, 17(168): 20200065.

[37] Bigall N C, Härtling T, Klose M, Klose M, Simon P, Eng L M, Eychmüller A. Monodisperse platinum nanospheres with adjustable diameters from 10 to 100 nm: synthesis and distinct optical properties[J]. Nano lett., 2008, 8(12): 4588-4592.