Issue

Vol. 15 (2023)

Biocatalytic Buoyancy-Driven Nanobots for Autonomous Cell Recognition and Enrichment

https://doi.org/10.1007/s40820-023-01207-1
Ziyi Guo
School of Chemical Engineering, Australian Centre for NanoMedicine, The University of New South Wales, Sydney, NSW 2052, Australia
Chenchen Zhuang
General Intensive Care Unit, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of China
Yihang Song
Medical College, Northwest Minzu University, Lanzhou 730000, People’s Republic of China
Joel Yong
School of Chemical Engineering, Australian Centre for NanoMedicine, The University of New South Wales, Sydney, NSW 2052, Australia
Yi Li
School/Hospital of Stomatology, Lanzhou University, Lanzhou 730000, People’s Republic of China
Zhong Guo
Medical College, Northwest Minzu University, Lanzhou 730000, People’s Republic of China
Biao Kong
Department of Chemistry, Shanghai Key Lab of Molecular Catalysis and Innovative Materials, Collaborative Innovation Center of Chemistry for Energy Materials, Fudan University, Shanghai 200438, People’s Republic of China
John M. Whitelock
Graduate School of Biomedical Engineering, The University of New South Wales, Sydney, NSW 2052, Australia
Joseph Wang
Department of Nanoengineering, University of California San Diego, La Jolla, CA 92093, USA
Kang Liang
School of Chemical Engineering, Australian Centre for NanoMedicine, The University of New South Wales, Sydney, NSW 2052, Australia

Corresponding Author: Kang Liang

kang.liang@unsw.edu.au

Nano-Micro Letters, Vol. 15 (2023), Article Number: 236

Abstract

Autonomously self-propelled nanoswimmers represent the next-generation nano-devices for bio- and environmental technology. However, current nanoswimmers generate limited energy output and can only move in short distances and duration, thus are struggling to be applied in practical challenges, such as living cell transportation. Here, we describe the construction of biodegradable metal–organic framework based nanobots with chemically driven buoyancy to achieve highly efficient, long-distance, directional vertical motion to “find-and-fetch” target cells. Nanobots surface-functionalized with antibodies against the cell surface marker carcinoembryonic antigen are exploited to impart the nanobots with specific cell targeting capacity to recognize and separate cancer cells. We demonstrate that the self-propelled motility of the nanobots can sufficiently transport the recognized cells autonomously, and the separated cells can be easily collected with a customized glass column, and finally regain their full metabolic potential after the separation. The utilization of nanobots with easy synthetic pathway shows considerable promise in cell recognition, separation, and enrichment.


Highlights:
1 A self-propelled, biocatalytic buoyancy-driven metal–organic framework (MOF) nanobot is developed.
2 The anti-carcinoembryonic antigen antibody functionalized MOF nanobot demonstrates directional vertical motion to “find-and-fetch” cancer cells from mixed cell population.
3 The captured cells can be recovered with full metabolic potential.

Keywords

Nanobots Surface functionalization Cell recognition Cell separation Metal–organic frameworks
Guo, Ziyi, Chenchen Zhuang, Yihang Song, Joel Yong, Yi Li, Zhong Guo, Biao Kong, John M. Whitelock, Joseph Wang, and Kang Liang. 2023. “Biocatalytic Buoyancy-Driven Nanobots for Autonomous Cell Recognition and Enrichment”. Nano-Micro Letters 15 (October):236. https://doi.org/10.1007/s40820-023-01207-1.
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References
  1. A. Gross, J. Schoendube, S. Zimmermann, M. Steeb, R. Zengerle et al., Technologies for single-cell isolation. Int. J. Mol. Sci. 16, 16897 (2015). https://doi.org/10.3390/ijms160816897
  2. P. De Coppi, G. Bartsch, M.M. Siddiqui, T. Xu, C.C. Santos et al., Isolation of amniotic stem cell lines with potential for therapy. Nat. Biotechnol. 25, 100 (2007). https://doi.org/10.1038/nbt1274
  3. M. Tatullo, M. Marrelli, K.M. Shakesheff, L.J. White, Dental pulp stem cells: function, isolation and applications in regenerative medicine. J. Tissue Eng. Regen. Med. 9, 1205 (2015). https://doi.org/10.1002/term.1899
  4. Z. Li, H. Cai, Z. Li, L. Ren, X. Ma et al., A tumor cell membrane-coated self-amplified nanosystem as a nanovaccine to boost the therapeutic effect of anti-PD-L1 antibody. Bioact. Mater. 21, 299 (2023). https://doi.org/10.1016/j.bioactmat.2022.08.028
  5. P. Tan, X. Chen, H. Zhang, Q. Wei, K. Luo, Artificial intelligence aids in development of nanomedicines for cancer management. Semin. Cancer Biol. 89, 61 (2023). https://doi.org/10.1016/j.semcancer.2023.01.005
  6. C. Kudo Saito, Y. Ozaki, H. Imazeki, H. Hayashi, J. Masuda et al., Targeting oncoimmune drivers of cancer metastasis. Cancers 13, 554 (2021)
  7. J.W. Kim, E.I. Galanzha, D.A. Zaharoff, R.J. Griffin, V.P. Zharov, Nanotheranostics of circulating tumor cells, infections and other pathological features in vivo. Mol. Pharm. 10, 813 (2013). https://doi.org/10.1021/mp300577s
  8. W. Lee, P. Tseng, D. Di Carlo, Microtechnology for cell manipulation and sorting. Springer (2017). https://doi.org/10.1007/978-3-319-44139-9
  9. A. Dalili, E. Samiei, M. Hoorfar, A review of sorting, separation and isolation of cells and microbeads for biomedical applications: microfluidic approaches. Analyst 144, 87 (2018). https://doi.org/10.1039/C8AN01061G
  10. C.M. Yousuff, E.T.W. Ho, I. Hussain, N.H.B. Hamid, Microfluidic platform for cell isolation and manipulation based on cell properties. Micromachines 8, 15 (2017). https://doi.org/10.3390/mi8010015
  11. J. Wu, Q. Chen, J.-M. Lin, Microfluidic technologies in cell isolation and analysis for biomedical applications. Analyst 142, 421 (2017). https://doi.org/10.1039/C6AN01939K
  12. A. Lee, J. Park, M. Lim, V. Sunkara, S.Y. Kim et al., All-in-one centrifugal microfluidic device for size-selective circulating tumor cell isolation with high purity. Anal. Chem. 86, 11349 (2014). https://doi.org/10.1021/ac5035049
  13. H. Başağaoğlu, J. Blount, S. Succi, C.J. Freitas, Combined effects of fluid type and p shape on ps flow in microfluidic platforms. Microfluid. Nanofluid. 23, 84 (2019). https://doi.org/10.1007/s10404-019-2251-9
  14. G. Hvichia, Z. Parveen, C. Wagner, M. Janning, J. Quidde et al., A novel microfluidic platform for size and deformability based separation and the subsequent molecular characterization of viable circulating tumor cells. Int. J. Cancer 138, 2894 (2016). https://doi.org/10.1002/ijc.30007
  15. S.M. McFaul, B.K. Lin, H. Ma, Cell separation based on size and deformability using microfluidic funnel ratchets. Lab Chip 12, 2369 (2012). https://doi.org/10.1039/C2LC21045B
  16. Y. Zhang, X. Chen, Blood cells separation microfluidic chip based on dielectrophoretic force. J. Braz. Soc. Mech. Sci. Eng. 42, 206 (2020). https://doi.org/10.1007/s40430-020-02284-8
  17. A. Salmanzadeh, L. Romero, H. Shafiee, R.C. Gallo-Villanueva, M.A. Stremler et al., Isolation of prostate tumor initiating cells (TICs) through their dielectrophoretic signature. Lab Chip 12, 182 (2012). https://doi.org/10.1039/C1LC20701F
  18. G. Wang, H. Benasutti, J.F. Jones, G. Shi, M. Benchimol et al., Isolation of breast cancer CTCs with multitargeted buoyant immunomicrobubbles. Coll. Surf. B 161, 200 (2018). https://doi.org/10.1016/j.colsurfb.2017.10.060
  19. S. Siemer, D. Wünsch, A. Khamis, Q. Lu, A. Scherberich et al., Nano meets micro-translational nanotechnology in medicine: nano-based applications for early tumor detection and therapy. Nanomaterials 10, 383 (2020). https://doi.org/10.3390/nano10020383
  20. J. Chen, Y. Xu, Y. Lu, W. Xing, Isolation and visible detection of tumor-derived exosomes from plasma. Anal. Chem. 90, 14207 (2018). https://doi.org/10.1021/acs.analchem.8b03031
  21. J. Peng, Q. Zhao, W. Zheng, W. Li, P. Li et al., Peptide-functionalized nanomaterials for the efficient isolation of HER2-positive circulating tumor cells. ACS Appl. Mater. Interfaces 9, 18423 (2017). https://doi.org/10.1021/acsami.7b03905
  22. J. Li, W. Gao, R. Dong, A. Pei, S. Sattayasamitsathit et al., Nanomotor lithography. Nat. Commun. 5, 5026 (2014). https://doi.org/10.1038/ncomms6026
  23. J. Sun, M. Mathesh, W. Li, D.A. Wilson, Enzyme-powered nanomotors with controlled size for biomedical applications. ACS Nano 13, 10191 (2019). https://doi.org/10.1021/acsnano.9b03358
  24. Y. Tu, F. Peng, D.A. Wilson, Motion manipulation of micro- and nanomotors. Adv. Mater. 29, 1701970 (2017). https://doi.org/10.1002/adma.201701970
  25. Q. Yang, L. Xu, W. Zhong, Q. Yan, Y. Gao et al., Recent advances in motion control of micro/nanomotors. Adv. Intell. Syst. 2, 2000049 (2020). https://doi.org/10.1002/aisy.202000049
  26. Q. Chi, Z. Wang, F. Tian, J. You, S. Xu, A review of fast bubble-driven micromotors powered by biocompatible fuel: low-concentration fuel, bioactive fluid and enzyme. Micromachines 9, 537 (2018). https://doi.org/10.3390/mi9100537
  27. X. Ma, X. Wang, K. Hahn, S. Sanchez, Motion control of urea-powered biocompatible hollow microcapsules. ACS Nano 10, 3597 (2016). https://doi.org/10.1021/acsnano.5b08067
  28. J. Wang, R. Dong, H. Wu, Y. Cai, B. Ren, A review on artificial micro/nanomotors for cancer-targeted delivery, diagnosis, and therapy. Nano-Micro Lett. 12, 11 (2019). https://doi.org/10.1007/s40820-019-0350-5
  29. F. Peng, Y. Tu, D.A. Wilson, Micro/nanomotors towards in vivo application: cell, tissue and biofluid. Chem. Soc. Rev. 46, 5289 (2017). https://doi.org/10.1039/C6CS00885B
  30. Z. Guo, T. Wang, A. Rawal, J. Hou, Z. Cao et al., Biocatalytic self-propelled submarine-like metal-organic framework microps with pH-triggered buoyancy control for directional vertical motion. Mater. Today 28, 10 (2019). https://doi.org/10.1016/j.mattod.2019.04.022
  31. Z. Guo, J. Liu, Y. Li, J.A. McDonald, M.Y. Bin Zulkifli et al., Biocatalytic metal-organic framework nanomotors for active water decontamination. Chem. Commun. 56, 14837 (2020). https://doi.org/10.1039/D0CC06429G
  32. D. Vilela, J. Parmar, Y. Zeng, Y. Zhao, S. Sanchez, Graphene-based microbots for toxic heavy metal removal and recovery from water. Nano Lett. 16, 2860 (2016). https://doi.org/10.1021/acs.nanolett.6b00768
  33. D. Kagan, S. Campuzano, S. Balasubramanian, F. Kuralay, G.-U. Flechsig et al., Functionalized micromachines for selective and rapid isolation of nucleic acid targets from complex samples. Nano Lett. 11, 2083 (2011). https://doi.org/10.1021/nl2005687
  34. S. Campuzano, J. Orozco, D. Kagan, M. Guix, W. Gao et al., Bacterial isolation by lectin-modified microengines. Nano Lett. 12, 396 (2012). https://doi.org/10.1021/nl203717q
  35. S. Balasubramanian, D. Kagan, C.-M. Jack Hu, S. Campuzano, M.J. Lobo-Castañon et al., Micromachine-enabled capture and isolation of cancer cells in complex media. Angew. Chem. Int. Ed. 50, 4161 (2011). https://doi.org/10.1002/anie.201100115
  36. F. Kuralay, S. Sattayasamitsathit, W. Gao, A. Uygun, A. Katzenberg et al., Self-propelled carbohydrate-sensitive microtransporters with built-in boronic acid recognition for isolating sugars and cells. J. Am. Chem. Soc. 134, 15217 (2012). https://doi.org/10.1021/ja306080t
  37. H. Xu, M. Medina-Sanchez, O.G. Schmidt, Magnetic micromotors for multiple motile sperm cells capture, transport, and enzymatic release. Angew. Chem. Int. Ed. 59, 15029 (2020). https://doi.org/10.1002/anie.202005657
  38. B. Chen, Y. Jia, J. Zhao, H. Li, W. Dong et al., Assembled hemoglobin and catalase nanotubes for the treatment of oxidative stress. J. Phys. Chem. C 117, 19751 (2013). https://doi.org/10.1021/jp407164q
  39. C. Yim, H. Lee, S. Lee, S. Jeon, One-step immobilization of antibodies on ZIF-8/Fe3O4 hybrid nanops for the immunoassay of Staphylococcus aureus. RSC Adv. 7, 1418 (2017). https://doi.org/10.1039/C6RA25527B
  40. H. Sharma, R. Mutharasan, Half antibody fragments improve biosensor sensitivity without loss of selectivity. Anal. Chem. 85, 2472 (2013). https://doi.org/10.1021/ac3035426
  41. S. Jeong, J.Y. Park, M.G. Cha, H. Chang, Y.I. Kim et al., Highly robust and optimized conjugation of antibodies to nanops using quantitatively validated protocols. Nanoscale 9, 2548 (2017). https://doi.org/10.1039/C6NR04683E
  42. K. Liang, R. Ricco, C.M. Doherty, M.J. Styles, S. Bell et al., Biomimetic mineralization of metal-organic frameworks as protective coatings for biomacromolecules. Nat. Commun. 6, 7240 (2015). https://doi.org/10.1038/ncomms8240
  43. K. Liang, C.J. Coghlan, S.G. Bell, C. Doonan, P. Falcaro, Enzyme encapsulation in zeolitic imidazolate frameworks: a comparison between controlled co-precipitation and biomimetic mineralisation. Chem. Commun. 52, 473 (2016). https://doi.org/10.1039/C5CC07577G
  44. A.R. Sousa, M.J. Oliveira, B. Sarmento, Impact of CEA-targeting nanops for drug delivery in colorectal cancer. J. Pharmacol Exp. Ther. 370, 657 (2019). https://doi.org/10.1124/jpet.118.254441
  45. C.-M.J. Hu, S. Kaushal, H.S.T. Cao, S. Aryal, M. Sartor et al., Half-antibody functionalized lipid−polymer hybrid nanops for targeted drug delivery to carcinoembryonic antigen presenting pancreatic cancer cells. Mol. Pharm. 7, 914 (2010). https://doi.org/10.1021/mp900316a
  46. S. Ohtsukasa, S. Okabe, H. Yamashita, T. Iwai, K. Sugihara, Increased expression of CEA and MHC class I in colorectal cancer cell lines exposed to chemotherapy drugs. J. Cancer Res. Clin. Oncol. 129, 719 (2003). https://doi.org/10.1007/s00432-003-0492-0
  47. C.-X. Zheng, W.H. Zhan, J.-Z. Zhao, D. Zheng, D.-P. Wang et al., Prognostic value of preoperative serum levels of CEA, CA19-9 and CA72-4 in patients with colorectal cancer. World J. Gastroenterol. 7, 431 (2001). https://doi.org/10.3748/wjg.v7.i3.431
  48. S. Kaushal, M.K. McElroy, G.A. Luiken, M.A. Talamini, A. Moossa et al., Fluorophore-conjugated anti-CEA antibody for the intraoperative imaging of pancreatic and colorectal cancer. J. Gastrointest. Surg. 12, 1938 (2008). https://doi.org/10.1007/s11605-008-0581-0
  49. X. Ni, X. Bai, Y. Mao, Y. Shao, J. Wu et al., The clinical value of serum CEA, CA19-9, and CA242 in the diagnosis and prognosis of pancreatic cancer. Eur. J. Surg. Oncol. 31, 164 (2005). https://doi.org/10.1016/j.ejso.2004.09.007
  50. Y. Fujita, M. Terashima, Y. Hoshino, S. Ohtani, S. Kashimura et al., Detection of cancer cells disseminated in bone marrow using real-time quantitative RT-PCR of CEA, CK19, and CK20 mRNA in patients with gastric cancer. Gastric Cancer 9, 308 (2006). https://doi.org/10.1007/s10120-006-0398-z
  51. J. Yong, A.S. Mellick, J. Whitelock, J. Wang, K. Liang, A biomolecular toolbox for precision nanomotors. Adv. Mater. 35, 2205746 (2023). https://doi.org/10.1002/adma.202205746
  52. R. Alonso, P. Jimenez-Meneses, J. Garcia-Ruperez, M.J. Banuls, A. Maquieira, Thiol-ene click chemistry towards easy microarraying of half-antibodies. Chem. Commun. 54, 6144 (2018). https://doi.org/10.1039/C8CC01369A
  53. B.N. Lourenco, R.F. Pereira, C.C. Barrias, C. Fischbach, C. Oliveira et al., Engineering modular half-antibody conjugated nanops for targeting CD44v6-expressing cancer cells. Nanomaterials 11, 295 (2021). https://doi.org/10.3390/nano11020295
  54. Z. Guo, Y. Wu, Z. Xie, J. Shao, J. Liu et al., Self-propelled initiative collision at microelectrodes with vertically mobile micromotors. Angew. Chem. Int. Ed. 61, e202209747 (2022). https://doi.org/10.1002/anie.202209747
  55. Y. Zheng, H. Zhao, Y. Cai, B. Jurado-Sánchez, R. Dong, Recent advances in one-dimensional micro/nanomotors: fabrication, propulsion and application. Nano-Micro Lett. 15, 20 (2023). https://doi.org/10.1007/s40820-022-00988-1
  56. Y. Ge, M. Liu, L. Liu, Y. Sun, H. Zhang et al., Dual-Fuel-Driven Bactericidal Micromotor. Nano-Micro Lett. 8, 157–164 (2016). https://doi.org/10.1007/s40820-015-0071-3
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