SpringerLink
Log in

Magnetic guanidyl–functionalized covalent organic framework composite: a platform for specific capture and isolation of phosphopeptides and exosomes

  • Original Paper
  • Published:
Microchimica Acta Aims and scope Submit manuscript

Abstract

A guanidine-functionalized (GF) covalent organic framework (COF) nanocomposite has been developed by a post-synthetic approach for specific capture and separation of phosphopeptides and exosomes. The abundant binding sites on COF can immobilize a large number of gold nanoparticles (AuNPs), which can be used to react with amino groups to graft polyethyleneimine (PEI). Finally, Fe3O4@COF@Au@PEI-GF is obtained through the reaction of PEI and guanidyl group for phosphopeptides and exosomes detection. This composite shows a low detection limit (0.02 fmol), size exclusion effect (β-casein digests:Albumin from bovine serum protein = 1:10,000), good reusability (10 cycles), and high selectivity (β-casein digests:Albumin from bovine serum digests = 1:10,000). For complex biological sample, 4 phosphopeptides can be successfully identified from human serum. Furthermore, for the first time, we used guanidyl-functionalized probe to capture exosomes in human serum, providing a new method for enriching exosomes. The above experiments showed that Fe3O4@COF@Au@PEI-GF not only effectively enrich phosphopeptides and remove macromolecular proteins, but also successfully separate and capture exosomes. This demonstrates the great potential of this composite for the specific enrichment of phosphopeptides and isolation of exosomes.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Brazil)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. 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, Worms DP, Kalluri R (2015) Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature 523:177-U82. https://doi.org/10.1038/nature14581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Tauro BJ, Greening DW, Mathias RA, Ji H, Mathivanan S, Scott AM, Simpson RJ (2012) Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes. Methods 56:293–304. https://doi.org/10.1016/j.ymeth.2012.01.002

    Article  CAS  PubMed  Google Scholar 

  3. Wei HX, Chen JY, Wang SL, Fu FH, Zhu X, Wu CY, Liu ZJ, Zhong GX, Lin JH (2019) A nanodrug consisting of doxorubicin and exosome derived from mesenchymal stem cells for osteosarcoma treatment in vitro. Int J Nanomedicine 14:8603–8610. https://doi.org/10.2147/IJN.S218988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Webber J, Steadman R, Mason MD, Tabi Z, Clayton A (2010) Cancer exosomes trigger fibroblast to myofibroblast differentiation. Cancer Res 70:9621–9630. https://doi.org/10.1158/0008-5472.CAN-10-1722

    Article  CAS  PubMed  Google Scholar 

  5. **ong FF, Jia JX, Ma JT, Jia Q (2022) Glutathione-functionalized magnetic thioether-COFs for the simultaneous capture of urinary exosomes and enrichment of exosomal glycosylated and phosphorylated peptides. Nanoscale 14:853–864. https://doi.org/10.1039/d1nr06587d

    Article  CAS  PubMed  Google Scholar 

  6. Kang YT, Kim YJ, Bu J, Cho YH, Han SW, Moon BI (2017) High-purity capture and release of circulating exosomes using an exosome-specific dual-patterned immunofiltration (ExoDIF) device. Nanoscale 9:13495–13505. https://doi.org/10.1039/c7nr04557c

    Article  CAS  PubMed  Google Scholar 

  7. Hwang DW (2019) Perspective in nuclear theranostics using exosome for the brain. Med Mol Imaging 53:108–114. https://doi.org/10.1007/s13139-018-00567-6

    Article  Google Scholar 

  8. Lin SJ, Yu ZX, Chen D, Wang ZG, Miao JM, Li QC, Zhang DY, Song J, Cui DX (2020) Progress in microfluidics-based exosome separation and detection technologies for diagnostic applications. Small 16:1903916. https://doi.org/10.1002/smll.201903916

    Article  CAS  Google Scholar 

  9. Singh K, Nalabotala R, Koo KM, Bose S, Nayak R, Shiddiky MJA (2021) Separation of distinct exosome subpopulations: isolation and characterization approaches and their associated challenges. Analyst 146:3731–3749. https://doi.org/10.1039/d1an00024a

    Article  CAS  PubMed  Google Scholar 

  10. Sun NR, Yu HL, Wu H, Shen XZ, Deng CH (2021) Advanced nanomaterials as sample technique for bio-analysis. Trac-Trends Anal Chem 135:116168. https://doi.org/10.1016/j.trac.2020.116168

    Article  CAS  Google Scholar 

  11. Khodashenas S, Khalili S, Moghadam MF (2019) A cell ELISA based method for exosome detection in diagnostic and therapeutic applications. Biotechnol Lett 41:523–531. https://doi.org/10.1007/s10529-019-02667-5

    Article  CAS  PubMed  Google Scholar 

  12. Riva P, Battaglia C, Venturin M (2019) Emerging role of genetic alterations affecting exosome biology in neurodegenerative diseases. Int J Mol Sci 20:4113. https://doi.org/10.3390/ijms20174113

    Article  CAS  PubMed Central  Google Scholar 

  13. Zhang N, Hu XF, Chen HL, Deng CH, Sun NAR (2021) Specific enrichment and glycosylation discrepancy profiling of cellular exosomes by dual-affinity probe. Chem Commun 57:6249–6252. https://doi.org/10.1039/d1cc01530c

    Article  CAS  Google Scholar 

  14. Zhang N, Sun NR, Deng CH (2020) A hydrophilic magnetic MOF for the consecutive enrichment of exosomes and exosomal phosphopeptides. Chem Commun 56:13999–14002. https://doi.org/10.1039/d0cc06147f

    Article  CAS  Google Scholar 

  15. Cao F, Gao Y, Chu Q, Wu Q, Zhao L, Lan T, Zhao L (2019) Proteomics comparison of exosomes from serum and plasma between ultracentrifugation and polymer-based precipitation kit methods. Electrophoresis 40:3092–3098. https://doi.org/10.1002/elps.201900295

    Article  CAS  PubMed  Google Scholar 

  16. Sun NR, Wang JW, Yao Z, Chen HM, Deng CH (2019) Magnetite nanoparticles coated with mercaptosuccinic acid-modified mesoporous titania as a hydrophilic sorbent for glycopeptides and phosphopeptides prior to their quantitation by LC-MS/MS. Microchim Acta 186:159. https://doi.org/10.1007/s00604-019-3274-3

    Article  CAS  Google Scholar 

  17. Sun NR, Wang ZD, Wang JW, Chen HM, Wu H, Shen S, Deng CH (2019) Hydrophilic tripeptide combined with magnetic titania as a multipurpose platform for universal enrichment of phospho- and glycopeptides. J Chromatogr A 1595:1–10. https://doi.org/10.1016/j.chroma.2019.02.039

    Article  CAS  PubMed  Google Scholar 

  18. Liu B, Wang BC, Yan YH, Tang KQ, Ding CF (2021) Efficient separation of phosphopeptides employing a Ti/Nb-functionalized core-shell structure solid-phase extraction nanosphere. Microchim Acta 188:32. https://doi.org/10.1007/s00604-020-04652-6

    Article  CAS  Google Scholar 

  19. Chu HM, Zheng HY, Yao JZ, Sun NR, Yan GQ, Deng CH (2020) Magnetic metal phenolic networks: expanding the application of a promising nanoprobe to phosphoproteomics research. Chem Commun 56:11299–11302. https://doi.org/10.1039/d0cc04615a

    Article  CAS  Google Scholar 

  20. Du JL, Yan YH, Tang KQ, Ding CF (2021) Modified carbon nanotubes decorated with ZIFs as new immobilized metal ion affinity chromatography platform for enrichment of phosphopeptides. ChemistrySelect 6:1313–1319. https://doi.org/10.1002/slct.202004650

    Article  CAS  Google Scholar 

  21. Luo B, Zhou XX, Jiang PP, Yi QY, Lan F, Wu Y (2018) PAMA-Arg brushes-functionalized magnetic composite nanospheres for highly effective enrichment of the phosphorylated biomolecules. J Mater Chem B 6:3969–3978. https://doi.org/10.1039/c8tb00705e

    Article  CAS  PubMed  Google Scholar 

  22. Jiang DD, Duan LM, Jia Q, Liu JH (2020) Glycocyamine functionalized magnetic layered double hydroxides with multiple affinity sites for trace phosphopeptides enrichment. Anal Chim Acta 1136:25–33. https://doi.org/10.1016/j.aca.2020.07.057

    Article  CAS  PubMed  Google Scholar 

  23. **e ZH, Yan YH, Tang KQ, Ding CF (2022) Post-synthesis modification of covalent organic frameworks for ultrahigh enrichment of low-abundance glycopeptides from human saliva and serum. Talanta 236:122831. https://doi.org/10.1016/j.talanta.2021.122831

    Article  CAS  PubMed  Google Scholar 

  24. Gao CH, Bai J, He YT, Zheng Q, Ma WD, Lei ZX, Zhang MY, Wu J, Fu FF, Lin Z (2019) Postsynthetic functionalization of Zr4+-immobilized core−shell structured magnetic covalent organic frameworks for selective enrichment of phosphopeptides. ACS Appl Mater Interfaces 11:13735–13741. https://doi.org/10.1021/acsami.9b03330

    Article  CAS  PubMed  Google Scholar 

  25. Chen L, He YT, Lei ZX, Gao CL, **e Q, Tong P, Lin Z (2018) Preparation of core-shell structured magnetic covalent organic framework nanocomposites for magnetic solid-phase extraction of bisphenols from human serum sample. Talanta 181:296–304. https://doi.org/10.1016/j.talanta.2018.01.036

    Article  CAS  PubMed  Google Scholar 

  26. You LJ, Xu K, Ding GJ, Shi XM, Li JM, Wang SY, Wang JB (2020) Facile synthesis of Fe3O4@COF covalent organic frameworks for the adsorption of bisphenols from aqueous solution. J Mol Liq 320:114456. https://doi.org/10.1016/j.molliq.2020.114456

    Article  CAS  Google Scholar 

  27. Baldwin LA, Crowe JW, Pyles DA, McGrier PL (2016) Metalation of a mesoporous three-dimensional covalent organic framework. J Am Chem Soc 138:15134–15137. https://doi.org/10.1021/jacs.6b10316

    Article  CAS  PubMed  Google Scholar 

  28. Lu YY, Wang XL, Wang LL, Zhang W, Wei JJ, Lin JM, Zhao RS (2021) Room-temperature synthesis of amino-functionalized magnetic covalent organic frameworks for efficient extraction of perfluoroalkyl acids in environmental water samples. J Hazard Mater 407:124782. https://doi.org/10.1016/j.jhazmat.2020.124782

    Article  CAS  PubMed  Google Scholar 

  29. Wang JX, Li J, Gao MX, Zhang XM (2018) Recent advances in covalent organic frameworks for separation and analysis of complex samples. TrAC Trends Anal Chem 108:98–109. https://doi.org/10.1016/j.trac.2018.07.013

    Article  CAS  Google Scholar 

  30. Fu QB, Jiang HL, Qiao LQ, Sun X, Wang ML, Zhao RS (2020) Effective enrichment and detection of trace polybrominated diphenyl ethers in water samples based on magnetic covalent organic framework nanospheres coupled with chromatography-mass spectrometry. J Chromatogr A 1630:461534. https://doi.org/10.1016/j.chroma.2020.461534

    Article  CAS  PubMed  Google Scholar 

  31. Ren JF, Shen S, Pang ZQ, Lu XH, Deng CH, Jiang XG (2011) Facile synthesis of superparamagnetic Fe3O4@Au nanoparticles for photothermal destruction of cancer cells. Chem Commun 47:11692–11694. https://doi.org/10.1039/c1cc15528h

    Article  CAS  Google Scholar 

  32. Ma YY, Zhao YX, Xu XT, Ding SJ, Li YH (2021) Magnetic covalent organic framework immobilized gold nanoparticles with high-efficiency catalytic performance for chemiluminescent detection of pesticide triazophos. Talanta 235:122798. https://doi.org/10.1016/j.talanta.2021.122798

    Article  CAS  PubMed  Google Scholar 

  33. Yang CJ, Yu HL, Hu XF, Chen HL, Wu H, Deng CH, Sun NR (2021) Gold-Doped covalent-organic framework reveals specific serum metabolic fingerprints as point of Crohn’s disease diagnosis. Adv Funct Mater 31:2105478. https://doi.org/10.1002/adfm.202105478

    Article  CAS  Google Scholar 

  34. Jiang B, Qu YY, Zhang LH, Liang Z, Zhang YK (2016) 4-Mercaptophenylboronic acid functionalized graphene oxide composites: preparation, characterization and selective enrichment of glycopeptides. Anal Chim Acta 912:41–48. https://doi.org/10.1016/j.aca.2016.01.018

    Article  CAS  PubMed  Google Scholar 

  35. Liu HL, Lian B (2018) A guanidyl-functionalized TiO2 nanoparticle-anchored graphene nanohybrid for enhanced capture of phosphopeptides. RSC Adv 8:29476–29481. https://doi.org/10.1039/c8ra90074d

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Li JY, Zhang S, Gao W, Hua Y, Lian HZ (2020) Guanidyl-Functionalized magnetic bimetallic MOF nanocomposites developed for selective enrichment of phosphopeptides. ACS Sustainable Chem Eng 8:16422–16429. https://doi.org/10.1021/acssuschemeng.0c04118

    Article  CAS  Google Scholar 

  37. Zhang N, Sun NR, Deng CH (2021) Rapid isolation and proteome analysis of urinary exosome based on double interactions of Fe3O4@TiO2-DNA aptamer. Talanta 221:121571. https://doi.org/10.1016/j.talanta.2020.121571

    Article  CAS  PubMed  Google Scholar 

  38. Smolarz M, Pietrowska M, Matysiak N, Mielańczyk Ł, Widłak P (2019) Proteome profiling of exosomes purified from a small amount of human serum: the problem of co-purified serum components. Proteomes 7(2):18. https://doi.org/10.3390/proteomes7020018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work is supported by National Natural Science Foundation of China (21927805), Natural Science Foundation of Zhejiang Province (LY22B050008), Major Science and Technology Projects in Ningbo (2020Z090), and the K. C. Wong Magna Fund in Ningbo University.

Author information

Authors and Affiliations

  1. Key Laboratory of Advanced Mass Spectrometry and Molecular Analysis of Zhejiang Province, Institute of Mass Spectrometry, School of Material Science and Chemical Engineering, Ningbo University, Ningbo, 315211, Zhejiang, China

    Bing Wang, Baichun Wang, Quanshou Feng, Yinghua Yan & Chuan-Fan Ding

  2. National Institute of Metrology, Bei**g, 100084, China

    **ang Fang & **nhua Dai

Authors
  1. Bing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Baichun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Quanshou Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. **ang Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. **nhua Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yinghua Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chuan-Fan Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to **nhua Dai or Yinghua Yan.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 5974 KB)

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, B., Wang, B., Feng, Q. et al. Magnetic guanidyl–functionalized covalent organic framework composite: a platform for specific capture and isolation of phosphopeptides and exosomes. Microchim Acta 189, 330 (2022). https://doi.org/10.1007/s00604-022-05394-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00604-022-05394-3

Keywords

Search

Navigation