Abstract
N-Acety-L-cysteine (NAC), enriched with multiple electron-rich groups involving –SH, –C=O, and –COOH, exhibits strong affinities to transition metal ions. Herein, NAC was adopted as the stabilizing agent to synthesize a series of peroxidase-like Pt nanoclusters (NCs) with different physicochemical properties. Both the cluster size and the charge state of NAC–Pt NCs are highly dependent upon the molar ratio of [K2PtCl4]/[NAC], contributing to different peroxidase mimicking activities. The most active Pt nanozyme (~ 1.7 nm), composed of 60% metallic Pt0 and 40% positively charged Pt2+ respectively, exhibits the Km of 0.132 mM for 3,3′,5,5′-tetramethylbenzidine and 35 mM for H2O2. Based on the heparin-activated enzymatic activity of NAC–Pt at pH 6.0, an ultrasensitive test was established for quantitative determination of heparin, giving the linear response of 0.5–20 μg/mL as well as the limit of detection of 2 × 10−3 μg/mL. This proposed method is also applicable in biological fluid for practical applications. Such a colorimetric method possesses several advantages involving high sensitivity, short response, eco-friendly synthesis, low consumption of material and energy, free of expensive instrument, as well as simple operation.
Graphic abstract
Similar content being viewed by others
References
Rabenstein DL. Heparin and heparan sulfate: structure and function. Nat Prod Rep. 2002;19(3):312–31.
Bergamaschini L, Rossi E, Vergani C, Simoni MGD. Alzheimer’s disease: another target for heparin therapy. Sci World J. 2009;9:891–908.
Cao R, Li BX. A simple and sensitive method for visual detection of heparin using positively-charged gold nanoparticles as colorimetric probes. Chem Commun. 2011;47(10):2865–7.
Walker CPR, Royston D. Thrombin generation and its inhibition: a review of the scientific basis and mechanism of action of anticoagulant therapies. Br J Anaesth. 2002;88:848–63.
Zhan RY, Fang Z, Liu B. Naked-eye detection and quantification of heparin in serum with a cationic polythiophene. Anal Chem. 2010;82:1326–33.
Capila I, Linhardt RJ. Heparin–protein interactions. Angew Chem Int Ed. 2002;41:390–412.
Guerrini M, Beccati D, Shriver Z, Naggi A, Viswanathan K, Bisio A, Capila I, Lansing JC, Guglieri S, Fraser B, Al-Hakim A, Gunay NS, Zhang Z, Robinson L, Buhse L, Nasr M, Woodcock J, Langer R, Venkataraman G, Linhardt RJ, Casu B, Torri G, Sasisekharan R. Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events. Nat Biotechnol. 2008;26:669–75.
Ding Y, Shi L, Wei H. A “turn on” fluorescent probe for heparin and its oversulfated chondroitin sulfate contaminant. Chem Sci. 2015;6:6361–6.
Ding Y, Zhou M, Wei H. A supercharged fluorescent protein based FRET sensing platform for detection of heparin contamination. Anal Methods. 2017;9:5593–7.
Hu Y, Guo W, Ding Y, Cheng H, Wei H. Modulating luminescence of Tb(3+) with biomolecules for sensing heparin and its contaminant OSCS. Biosens Bioelectron. 2016;86:858–63.
Zhao JN, Yi YH, Mi NX, Yin BD, Wei MJ, Chen Q, Li HT, Zhang YY, Yao SZ. Gold nanoparticle coupled with fluorophore for ultrasensitive detection of protamine and heparin. Talanta. 2013;116:951–7.
Zeng Y, Pei JJ, Wang LH, Shen AG, Hu JM. A sensitive sequential ‘on/off’ SERS assay for heparin with wider detection window and higher reliability based on the reversed surface charge changes of functionalized Au@Ag nanoparticles. Biosens Bioelectron. 2015;66:55–61.
Yin MY, Duan ZQ, Zhang CX, Feng LP, Wan YQ, Cai YY, Liu H, Li S, Wang H. A visualized colorimetric detection strategy for heparin in serum using a metal-free polymer nanozyme. Microchem J. 2019;145:864–71.
Fu XL, Chen LX, Li JH, Lin M, You HY, Wang WH. Label-free colorimetric sensor for ultrasensitive detection of heparin based on color quenching of gold nanorods by graphene oxide. Biosens Bioelectron. 2012;34:227–31.
Qu F, Liu YQ, Lao HL, Wang YP, You JM. Colorimetric detection of heparin with high sensitivity based on the aggregation of gold nanoparticles induced by polymer nanoparticles. New J Chem. 2017;41(19):10592–7.
Cheng HJ, Liu YF, Hu YH, Ding YB, Lin SC, Cao W, Wang Q, Wu JJX, Muhammad F, Zhao XZ, Zhao D, Li Z, Xing H, Wei H. Monitoring of heparin activity in live rats using metal-organic framework nanosheets as peroxidase mimics. Anal Chem. 2017;89(21):11552–9.
Chen ZG, Wang Z, Chen X, Xu HX, Liu JB. Chitosan-capped gold nanoparticles for selective and colorimetric sensing of heparin. J Nanopart Res. 2013;15:1930–9.
Li Y, Sun HC, Shi FP, Cai N, Lu LH, Su XG. Multi-positively charged dendrimeric nanoparticles induced fluorescence quenching of graphene quantum dots for heparin and chondroitin sulfate detection. Biosens Bioelectron. 2015;74:284–90.
Hemmateenejad B, Dorostkar S, Shakerizadeh SF, Shamsipur M. pH-independent optical sensing of heparin based on ionic liquid-capped gold nanoparticles. Analyst. 2013;138(17):4830–7.
You JG, Wang YT, Tseng WL. Adenosine-related compounds as an enhancer for peroxidase-mimicking activity of nanomaterials: application to sensing of heparin level in human plasma and total sulfate glycosaminoglycan content in synthetic cerebrospinal fluid. ACS Appl Mater Inter. 2018;10(44):37846–54.
Li J, Cheng M, Li MJ. A luminescent and colorimetric probe based on the functionalization of gold nanoparticles by ruthenium(ii) complexes for heparin detection. Analyst. 2017;142(19):3733–9.
Li S, Huang PC, Wu FY. Highly selective and sensitive detection of heparin based on competition-modulated assembly and disassembly of fluorescent gold nanoclusters. New J Chem. 2017;41(2):717–23.
Liu HL, Song PS, Wei RR, Li K, Tong AJ. A facile, sensitive and selective fluorescent probe for heparin based on aggregation-induced emission. Talanta. 2014;118:348–52.
Wu J, Wang X, Wang Q, Lou Z, Li S, Zhu Y, Qin L, Wei H. Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes (II). Chem Soc Rev. 2019;48(4):1004–76.
Wei H, Wang E. Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes. Chem Soc Rev. 2013;42(14):6060–93.
Wei H, Wang E. Fe3O4 magnetic nanoparticles as peroxidase mimetics and their applications in H2O2 and glucose detection. Anal Chem. 2008;80(6):2250–4.
He Y, Li X, Xu X, Pan J, Niu X. A cobalt-based polyoxometalate nanozyme with high peroxidase-mimicking activity at neutral pH for one-pot colorimetric analysis of glucose. J Mater Chem B. 2018;6(36):5750–5.
Niu X, Xu X, Li X, Pan J, Qiu F, Zhao H, Lan M. Surface charge engineering of nanosized CuS via acidic amino acid modification enables high peroxidase-mimicking activity at neutral pH for one-pot detection of glucose. Chem Commun. 2018;54(95):13443–6.
Wang X, Tang CL, Liu JJ, Zhang HZ, Wang J. Ultra-small CuS nanoparticles as peroxidase mimetics for sensitive and colorimetric detection of uric acid in human serum. Chin J Anal Chem. 2018;46(5):e1825–31.
You JG, Liu YW, Lu CY, Tseng WL, Yu CJ. Colorimetric assay of heparin in plasma based on the inhibition of oxidase-like activity of citrate-capped platinum nanoparticles. Biosens Bioelectron. 2017;92:442–8.
Hu LZ, Liao H, Feng LY, Wang M, Fu WS. Accelerating the peroxidase-like activity of gold nanoclusters at neutral pH for colorimetric detection of heparin and heparinase activity. Anal Chem. 2018;90(10):6247–52.
Li XX, Zheng SS, Zou T, Zhang JL, Li W, Fu Y. Highly active Pd nanocatalysts regulated by biothiols for suzuki coupling reaction. Catal Lett. 2018;148(11):3325–34.
Dai SD, Zhang JL, Fu Y, Li W. Biothiol-mediated synthesis of Pt nanoparticles on graphene nanoplates and their application in methanol electrooxidation. J Mater Sci. 2017;53(1):423–34.
Kang YJ, Oh JW, Kim YR, Kim JS, Kim H. Chiral gold nanoparticle-based electrochemical sensor for enantioselective recognition of 3,4-dihydroxyphenylalanine. Chem Commun. 2010;46(31):5665–7.
Zhang L, Hu Q, Li ZP, Zhang Y, Lu DT, Shuang SM, Choi MMF, Dong C. Chromatographic separation and mass spectrometric analysis of N-acetyl-l-cysteine-protected palladium nanoparticles. Anal Methods. 2017;9(31):4539–46.
He SB, Deng HH, Liu AL, Li GW, Lin XH, Chen W, Xia XH. Synthesis and peroxidase-like activity of salt-resistant platinum nanoparticles by using bovine serum albumin as the scaffold. Chem Cat Chem. 2014;6(6):1543–8.
Farrag M. Preparation, characterization and photocatalytic activity of size selected platinum nanoclusters. J Photoch Photobio A. 2016;318:42–50.
Shibu ES, Muhammed MAH, Tsukuda T, Pradeep T. Ligand exchange of Au25SG18 leading to functionalized gold clusters: spectroscopy, kinetics, and luminescence. J Phys Chem C. 2008;112(32):12168–76.
Ma Y, Pang Y, Liu F, Xu H, Shen X. Microwave-assisted ultrafast synthesis of silver nanoparticles for detection of Hg2+. Spectrochim Acta A. 2016;153:206–11.
Li W, Zhang HX, Zhang JL, Fu Y. Synthesis and sensing application of glutathione-capped platinum nanoparticles. Anal Methods. 2015;7(11):4464–71.
Acknowledgements
This study was funded by National Natural Science Foundation of China (21878225, 21776215).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no competing interests.
Electronic supplementary material
Below is the link to the electronic supplementary material.
About this article
Cite this article
Li, X., Huang, Q., Li, W. et al. N-Acety-L-Cysteine-Stabilized Pt Nanozyme for Colorimetric Assay of Heparin. J. Anal. Test. 3, 277–285 (2019). https://doi.org/10.1007/s41664-019-00108-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s41664-019-00108-w