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Polymer-enhanced peroxidase activity of ceria nanozyme for highly sensitive detection of alkaline phosphatase

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Abstract

Nanoceria have demonstrated a wide array of catalytic activity similar to natural enzymes, holding considerable significance in the colorimetric detection of alkaline phosphatase (ALP), which is a biomarker of various biological disorders. However, the issues of physiological stability and formation of protein corona, which are strongly related to their surface chemistry, limit their practical application. In this work, CeO2 nanoparticles characterized by enhanced dimensional uniformity and specific surface area were synthesized, followed by encapsulation with various polymers to further increase catalytic activity and physiological stability. Notably, the CeO2 nanoparticles encapsulated within each polymer exhibited improved catalytic characteristics, with PAA-capped CeO2 exhibiting the highest performance. We further demonstrated that the PAA-CeO2 obtained with enhanced catalytic activity was attributed to an increase in surface negative charge. PAA-CeO2 enabled the quantitative assessment of AA activity within a wide concentration range of 10 to 60 μM, with a detection limit of 0.111 μM. Similarly, it allowed for the evaluation of alkaline phosphatase activity throughout a broad range of 10 to 80 U/L, with a detection limit of 0.12 U/L. These detection limits provided adequate sensitivity for the practical detection of ALP in human serum.

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References

  1. Chen ZJ, Wu HL, Shen YD, Wang H, Zhang YF, Hammock B, et al. Phosphate-triggered ratiometric fluoroimmunoassay based on nanobody-alkaline phosphatase fusion for sensitive detection of 1-naphthol for the exposure assessment of pesticide carbaryl. J Hazard Mater. 2022;424:127411.

    Article  CAS  PubMed  Google Scholar 

  2. Shaban SM, Jo SB, Hafez E, Cho JH, Kim DH. A comprehensive overview on alkaline phosphatase targeting and reporting assays. Coord Chem Rev. 2022;465:214567.

    Article  CAS  Google Scholar 

  3. Ghosh SS, Wang J, Yannie PJ, Cooper RC, Sandhu YK, Kakiyama G, et al. Over-expression of intestinal alkaline phosphatase attenuates atherosclerosis. Circ Res. 2021;128(11):1646–59.

    Article  CAS  PubMed  Google Scholar 

  4. Peng C, Xing H, Xue Y, Wang J, Li J, Wang E. Ratiometric sensing of alkaline phosphatase based on the catalytical activity from Mn–Fe layered double hydroxide nanosheets. Nanoscale. 2020;12(3):2022–7.

    Article  CAS  PubMed  Google Scholar 

  5. Liu Y, Cavallaro PM, Kim B-M, Liu T, Wang H, Kühn F, et al. A role for intestinal alkaline phosphatase in preventing liver fibrosis. Theranostics. 2021;11(1):14.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Liu SG, Han L, Li N, Xiao N, Ju YJ, Li NB, et al. A fluorescence and colorimetric dual-mode assay of alkaline phosphatase activity via destroying oxidase-like CoOOH nanoflakes. J Mater Chem B. 2018;6(18):2843–50.

    Article  CAS  PubMed  Google Scholar 

  7. Han Y, Chen J, Li Z, Chen H, Qiu H. Recent progress and prospects of alkaline phosphatase biosensor based on fluorescence strategy. Biosens Bioelectron. 2020;148:111811.

    Article  CAS  PubMed  Google Scholar 

  8. Porat-Ophir C, Dergachev V, Belkin A, Vernick S, Freynd G, Katsnelson M, et al. Chip level agitation effects on the electrochemical sensing of alkaline-phosphatase expressed from integrated liver tissue. Sens Actuators, B Chem. 2015;213:465–73.

    Article  CAS  Google Scholar 

  9. Yang R, Yan X, Li Y, Zhang X, Chen J. Nitrogen-doped porous carbon-ZnO nanopolyhedra derived from ZIF-8: new materials for photoelectrochemical biosensors. ACS Appl Mater Interfaces. 2017;9(49):42482–91.

    Article  CAS  PubMed  Google Scholar 

  10. Koncki R, Ogończyk D, Głąb S. Potentiometric assay for acid and alkaline phosphatase. Anal Chim Acta. 2005;538(1–2):257–61.

    Article  CAS  Google Scholar 

  11. Sun D, Xu W, Liang C, Shi W, Xu S. Smart surface-enhanced resonance Raman scattering nanoprobe for monitoring cellular alkaline phosphatase activity during osteogenic differentiation. ACS Sensors. 2020;5(6):1758–67.

    Article  CAS  PubMed  Google Scholar 

  12. Zeng Y, Ren J-Q, Wang S-K, Mai J-M, Qu B, Zhang Y, et al. Rapid and reliable detection of alkaline phosphatase by a hot spots amplification strategy based on well-controlled assembly on single nanoparticle. ACS Appl Mater Interfaces. 2017;9(35):29547–53.

    Article  CAS  PubMed  Google Scholar 

  13. Ximenes VF, Campa A, Baader WJ, Catalani LH. Facile chemiluminescent method for alkaline phosphatase determination. Anal Chim Acta. 1999;402(1–2):99–104.

    Article  CAS  Google Scholar 

  14. Liu X, Mei X, Yang J, Li Y. Hydrogel-involved colorimetric platforms based on layered double oxide nanozymes for point-of-care detection of liver-related biomarkers. ACS Appl Mater Interfaces. 2022;14(5):6985–93.

    Article  CAS  PubMed  Google Scholar 

  15. Zheng XT, Ananthanarayanan A, Luo KQ, Chen P. Glowing graphene quantum dots and carbon dots: properties, syntheses, and biological applications. Small. 2015;11(14):1620–36.

    Article  CAS  PubMed  Google Scholar 

  16. Mao G, Zhang Q, Yang Y, Ji X, He Z. Facile synthesis of stable CdTe/CdS QDs using dithiol as surface ligand for alkaline phosphatase detection based on inner filter effect. Anal Chim Acta. 2019;1047:208–13.

    Article  CAS  PubMed  Google Scholar 

  17. Liu P, Li D, Kang M, Pan Y, Wen Z, Zhang Z, et al. Emerging applications of aggregation‐induced emission luminogens in bacterial biofilm imaging and antibiofilm theranostics. Small structures. 2023;4(5).

  18. Wang M, Liu H, Fan K. Signal amplification strategy design in nanozyme‐based biosensors for highly sensitive detection of trace biomarkers. Small Methods. 2023:2301049.

  19. Ye K, Niu X, Song H, Wang L, Peng Y. Combining CeVO4 oxidase-mimetic catalysis with hexametaphosphate ion induced electrostatic aggregation for photometric sensing of alkaline phosphatase activity. Anal Chim Acta. 2020;1126:16–23.

    Article  CAS  PubMed  Google Scholar 

  20. Bornscheuer UT, Huisman G, Kazlauskas R, Lutz S, Moore J, Robins K. Engineering the third wave of biocatalysis. Nature. 2012;485(7397):185–94.

    Article  CAS  PubMed  Google Scholar 

  21. Breaker RR. DNA enzymes. Nat Biotechnol. 1997;15(5):427–31.

    Article  CAS  PubMed  Google Scholar 

  22. Meunier B, De Visser SP, Shaik S. Mechanism of oxidation reactions catalyzed by cytochrome P450 enzymes. Chem Rev. 2004;104(9):3947–80.

    Article  CAS  PubMed  Google Scholar 

  23. Huang Y, Ren J, Qu X. Nanozymes: classification, catalytic mechanisms, activity regulation, and applications. Chem Rev. 2019;119(6):4357–412.

    Article  CAS  PubMed  Google Scholar 

  24. Song H, Niu X, Ye K, Wang L, Xu Y, Peng Y. A novel alkaline phosphatase activity sensing strategy combining enhanced peroxidase-mimetic feature of sulfuration-engineered CoO x with electrostatic aggregation. Anal Bioanal Chem. 2020;412:5551–61.

    Article  CAS  PubMed  Google Scholar 

  25. Wu J, Wang X, Wang Q, Lou Z, Li S, Zhu Y, et al. Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes (II). Chem Soc Rev. 2019;48(4):1004–76.

    Article  CAS  PubMed  Google Scholar 

  26. Wei H, Wang E. Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes. Chem Soc Rev. 2013;42(14):6060–93.

    Article  CAS  PubMed  Google Scholar 

  27. Kim YG, Lee Y, Lee N, Soh M, Kim D, Hyeon T. Ceria‐based therapeutic antioxidants for biomedical applications. Advanced Mater. 2023:2210819.

  28. Baldim V, Yadav N, Bia N, Graillot A, Loubat C, Singh S, et al. Polymer-coated cerium oxide nanoparticles as oxidoreductase-like catalysts. ACS Appl Mater Interfaces. 2020;12(37):42056–66.

    Article  CAS  PubMed  Google Scholar 

  29. Song H, Ye K, Peng Y, Wang L, Niu X. Facile colorimetric detection of alkaline phosphatase activity based on the target-induced valence state regulation of oxidase-mimicking Ce-based nanorods. J Mater Chem B. 2019;7(38):5834–41.

    Article  CAS  PubMed  Google Scholar 

  30. Li Y, Liu J. Nanozyme’s catching up: activity, specificity, reaction conditions and reaction types. Mater Horiz. 2021;8(2):336–50.

    Article  CAS  PubMed  Google Scholar 

  31. Asati A, Santra S, Kaittanis C, Nath S, Perez JM. Oxidase-like activity of polymer-coated cerium oxide nanoparticles. Angewandte Chemie - Int Edition. 2009;121(13):2344–8.

    Article  Google Scholar 

  32. Meng S, Yao Z, Liu J, Wang E, Li C, Jiang B, et al. Carbon dots capped cerium oxide nanoparticles for highly efficient removal and sensitive detection of fluoride. J Hazard Mater. 2022;435:128976.

    Article  CAS  PubMed  Google Scholar 

  33. Taniguchi T, Katsumata K-i, Omata S, Okada K, Matsushita N. Tuning growth modes of ceria-based nanocubes by a hydrothermal method. Crystal Growth Design. 2011;11(9):3754–60.

  34. Veitch NC. Horseradish peroxidase: a modern view of a classic enzyme. Phytochemistry. 2004;65(3):249–59.

    Article  CAS  PubMed  Google Scholar 

  35. Shi J, Yin T, Shen W. Effect of surface modification on the peroxidase-like behaviors of carbon dots. Colloids Surf, B. 2019;178:163–9.

    Article  CAS  Google Scholar 

  36. Henriquez C, Aliaga C, Lissi E. Formation and decay of the ABTS derived radical cation: a comparison of different preparation procedures. Int J Chem Kinet. 2002;34(12):659–65.

    Article  CAS  Google Scholar 

  37. Chu X, Shi Q. Versatile magnetic nanoparticles for spatially organized assemblies of enzyme cascades: a comprehensive investigation of catalytic performance. Chin J Chem. 2022;40(12):1437–46.

    Article  CAS  Google Scholar 

  38. Nolan M, Ganduglia-Pirovano MV. Enhanced oxidation activity from modified ceria: MnOx–ceria, CrOx–ceria and Mg doped VOx–ceria. Appl Catal B. 2016;197:313–23.

    Article  CAS  Google Scholar 

  39. Chen C, Yuan Q, Ni P, Jiang Y, Zhao Z, Lu Y. Fluorescence assay for alkaline phosphatase based on ATP hydrolysis-triggered dissociation of cerium coordination polymer nanoparticles. Analyst. 2018;143(16):3821–8.

    Article  CAS  PubMed  Google Scholar 

  40. Liu H, Li M, Xia Y, Ren X. A turn-on fluorescent sensor for selective and sensitive detection of alkaline phosphatase activity with gold nanoclusters based on inner filter effect. ACS Appl Mater Interfaces. 2017;9(1):120–6.

    Article  CAS  PubMed  Google Scholar 

  41. Goggins S, Naz C, Marsh BJ, Frost CG. Ratiometric electrochemical detection of alkaline phosphatase. Chem Commun. 2015;51(3):561–4.

    Article  CAS  Google Scholar 

  42. Jiang H, Wang X. Alkaline Phosphatase-Responsive Anodic Electrochemiluminescence of CdSe Nanoparticles. Anal Chem. 2012;84(16):6986–93.

    Article  CAS  PubMed  Google Scholar 

  43. Liu W, Chu L, Zhang C, Ni P, Jiang Y, Wang B, et al. Hemin-assisted synthesis of peroxidase-like Fe-N-C nanozymes for detection of ascorbic acid-generating bio-enzymes. Chem Eng J. 2021;415:128876.

    Article  CAS  Google Scholar 

  44. Li CM, Zhen SJ, Wang J, Li YF, Huang CZ. A gold nanoparticles-based colorimetric assay for alkaline phosphatase detection with tunable dynamic range. Biosens Bioelectron. 2013;43:366–71.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was financially supported by GDAS Project of Science and Technology Development (2022GDASZH-2022010101), Natural Science Foundation of China (Nos. 21603067, 22073025), and Research and Development Plan in Key Areas of Guangdong Province (No. 2022B1111040002).

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Authors

Contributions

Wang Qian: Conceptualization, Data curation, Writing - Original draft, Writing - Reviewing and editing.

Meng Song: Investigation, Methodology.

Zhou Gang: Funding acquisition, Investigation.

Shi Qingshan: Formal analysis.

Xu Ziqiang: Project administration, Data curation.

Xie Xiaobao: Supervision, Validation.

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Correspondence to Ziqiang Xu or Xiaobao Xie.

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Published in the topical collection featuring Nanozymes with guest editors Vipul Bansal, Sudipta Seal, and Hui Wei.

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Wang, Q., Meng, S., Zhou, G. et al. Polymer-enhanced peroxidase activity of ceria nanozyme for highly sensitive detection of alkaline phosphatase. Anal Bioanal Chem (2024). https://doi.org/10.1007/s00216-024-05307-8

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