Capture of live circulating tumor cells via unique surface charges from cancer patients by a novel nanotechnology

Abstract

Circulating tumor cells (CTCs) serve as a pivotal foundation for both fundamental oncological research and the precise evaluation of therapeutic interventions. However, the isolation of CTCs from clinical blood samples presents a multitude of sophisticated challenges, predominantly associated with the specificity of biomarkers and the sensitivity of detection techniques. In our previous study, we proposed a novel detection concept for CTCs based on a signature biophysical feature on the surface of cancer cells: a negative charge regulated by glycolytic processes. In this study, we have conducted experiments to ascertain the efficacy of this proposed method in capturing CTCs from clinical blood samples of individuals afflicted with solid tumors and leukemia. Our findings indicate that the method is capable of isolating tens of thousands of viable cancer cells from various metastatic solid cancers and leukemia using a mere 1 mL of blood. These cells were enumerated using cytological imaging that identified morphological characteristics indicative of malignancy. The outcomes of our study suggest that the negatively charged surface of cancer cells is a ubiquitous trait across both cultured cancer cell lines and fresh blood samples derived from cancer patients. Moreover, the capture technology employed in this study demonstrated superior performance in comparison to antecedent methodologies, enhancing the detection and documentation of CTCs for subsequent verification and analysis. This advancement holds significant promise for the improvement of diagnostic accuracy and the monitoring of therapeutic responses in oncology.

Keywords

circulating tumor cells / leukemia / nanomaterial-based CTCs detection technology / solid tumors

References

[1] T. J. Moss, D. G. Sanders, L. C. Lasky, B. Bostrom, Blood 1990, 76, 1879.

[2] L. E. Cortés-Hernández, S. Z. Eslami, K. Pantel, C. Alix-Panabières, Clin. Chem. 2020, 66, 97.

[3] J. Massagué, A. C. Obenauf, Nature 2016, 529, 298.

[4] H. Kantamneni, M. Zevon, M. J. Donzanti, X. Zhao, Y. Sheng, S. R. Barkund, L. H. McCabe, W. Banach-Petrosky, L. M. Higgins, S. Ganesan, R. E. Riman, C. M. Roth, M. C. Tan, M. C. Pierce, V. Ganapathy, P. V. Moghe, Nat. Biomed. Eng. 2017, 1, 993.

[5] M. Mazzone, G. Bergers, Annu. Rev. Physiol. 2019, 81, 535.

[6] X. Y. Li, M. Dong, X. Y. Zang, M. Y. Li, J. Y. Zhou, J. J. Ma, G. Y. Wang, Am. J. Transl Res. 2020, 12, 332.

[7] E. Schuster, R. Taftaf, C. Reduzzi, M. K. Albert, I. Romero-Calvo, H. Liu, Trends Cancer 2021, 7, 1020.

[8] S. Valastyan, R. A. Weinberg, Cell 2011, 147, 275.

[9] A. W. Lambert, D. R. Pattabiraman, R. A. Weinberg, Cell 2017, 168, 670.

[10] W. R. Liu, B. Zhang, C. Chen, Y. Li, X. Ye, D. J. Tang, J. C. Zhang, J. Ma, Y. L. Zhou, X. J. Fan, D. S. Yue, C. G. Li, H. Zhang, Y. C. Ma, Y. S. Huo, Z. F. Zhang, S. Y. He, C. L. Wang, Thorac. Cancer 2020, 11, 3234.

[11] R. Lawrence, M. Watters, C. R. Davies, K. Pantel, Y. J. Lu, Nat. Rev. Clin. Oncol. 2023, 20, 487.

[12] D. A. Arber, A. Orazi, R. Hasserjian, J. Thiele, M. J. Borowitz, M. M. Le Beau, C. D. Bloomfield, M. Cazzola, J. W. Vardiman, Blood 2016, 127, 2391.

[13] J. M. Jackson, J. B. Taylor, M. A. Witek, S. A. Hunsucker, J. P. Waugh, Y. Fedoriw, T. C. Shea, S. A. Soper, P. M. Armistead, Analyst 2016, 141, 640.

[14] M. T. Gabriel, L. R. Calleja, A. Chalopin, B. Ory, D. Heymann, Clin. Chem. 2016, 62, 571.

[15] K. C. Andree, G. van Dalum, L. W. Terstappen, Mol. Oncol. 2016, 10, 395.

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

[17] Y. Li, Q. Lu, H. Liu, J. Wang, P. Zhang, H. Liang, L. Jiang, S. Wang, Adv. Mater. 2015, 27, 6848.

[18] K. A. Hyun, T. Y. Lee, H. I. Jung, Anal. Chem. 2013, 85, 4439.

[19] I. Desitter, B. S. Guerrouahen, N. Benali-Furet, J. Wechsler, P. A. Jänne, Y. Kuang, M. Yanagita, L. Wang, J. A. Berkowitz, R. J. Distel, Y. E. Cayre, Anticancer Res. 2011, 31, 427.

[20] L. Wang, W. Asghar, U. Demirci, Y. Wan, Nano Today 2013, 8, 347.

[21] K. Pantel, C. Alix-Panabières, Nat. Rev. Clin. Oncol. 2019, 16, 409.

[22] T. M. Gorges, I. Tinhofer, M. Drosch, L. Röse, T. M. Zollner, T. Krahn, O. von Ahsen, BMC Cancer 2012, 12, 178.

[23] X. Zheng, J. L. Carstens, J. Kim, M. Scheible, J. Kaye, H. Sugimoto, C. C. Wu, V. S. LeBleu, R. Kalluri, Nature 2015, 527, 525.

[24] S. Ju, C. Chen, J. Zhang, L. Xu, X. Zhang, Z. Li, Y. Chen, J. Zhou, F. Ji, L. Wang, Biomark. Res. 2022, 10, 58.

[25] B. Hong, Y. Zu, Theranostics 2013, 3, 377.

[26] B. Chen, W. Le, Y. Wang, Z. Li, D. Wang, L. Ren, L. Lin, S. Cui, J. J. Hu, Y. Hu, P. Yang, R. C. Ewing, D. Shi, Z. Cui, Theranostics 2016, 6, 1887.

[27] D. Hanahan, R. A. Weinberg, Cell 2011, 144, 646.

[28] B. Faubert, K. Y. Li, L. Cai, C. T. Hensley, J. Kim, L. G. Zacharias, C. Yang, Q. N. Do, S. Doucette, D. Burguete, H. Li, G. Huet, Q. Yuan, T. Wigal, Y. Butt, M. Ni, J. Torrealba, D. Oliver, R. E. Lenkinski, C. R. Malloy, J. W. Wachsmann, J. D. Young, K. Kernstine, R. J. DeBerardinis, Cell 2017, 171, 358.

[29] D. Sasca, J. Szybinski, A. Schüler, V. Shah, J. Heidelberger, P. S. Haehnel, A. Dolnik, O. Kriege, E. M. Fehr, W. H. Gebhardt, G. Reid, C. Scholl, M. Theobald, L. Bullinger, P. Beli, T. Kindler, Blood 2019, 133, 2305.

[30] W. Le, B. Chen, Z. Cui, Z. Liu, D. Shi, Biophys. Rep. 2019, 5, 10.

[31] S. Harada, E. Agosto-Arroyo, J. A. Levesque, E. Alston, K. M. Janowski, G. M. Coshatt, I. A. Eltoum, Cancer Cytopathol 2015, 123, 480.

[32] A. I. Baba, C. Câtoi, in Comparative Oncology, The Publishing House of the Romanian Academy, Bucharest (RO) 2007.

[33] I. Singh, T. P. Lele, Results Probl. Cell Differ. 2022, 70, 443.

[34] K. Hashimoto, S. Nishimura, T. Ito, N. Oka, M. Akagi, Ann. Med. Surg. 2021, 68, 102581.

[35] B. M. Mohamed, M. P. Ward, M. Bates, C. D. Spillane, T. Kelly, C. Martin, M. Gallagher, S. Heffernan, L. Norris, J. Kennedy, F. A. Saadeh, N. Gleeson, D. A. Brooks, R. D. Brooks, S. Selemidis, S. O’Toole, J. J. O’Leary, Sci. Rep. 2023, 13, 3704.

[36] J. Xu, K. Liao, X. Yang, C. Wu, W. Wu, Mol. Cancer 2021, 20, 104.

[37] R. Negishi, H. Yamakawa, T. Kobayashi, M. Horikawa, T. Shimoyama, F. Koizumi, T. Sawada, K. Oboki, Y. Omuro, C. Funasaka, A. Kageyama, Y. Kanemasa, T. Tanaka, T. Matsunaga, T. Yoshino, Commun. Biol. 2022, 5, 20.

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2024 The Author(s). Interdisciplinary Medicine published by Wiley-VCH GmbH on behalf of Nanfang Hospital, Southern Medical University.