Aggregation-Induced Emission Enhancement of CdSe QDs by Protamine and its Application to Sensitively and Selectively Detect Heparin

Author(s): Jin-Xia Liu, Mei-Xia Wu*, Shou-Nian Ding*.

Journal Name: Current Analytical Chemistry

Volume 15 , Issue 5 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Heparin, it is commercially used as an anticoagulant in surgical procedures for the prevention of blood clotting. However, overdose and prolonged use of heparin often induce potentially fatal bleeding complication. So, it is of crucial importance to monitor closely heparin levels for the sake of health. In this work, a sensitive fluorescence sensing platform to detect heparin was set up based on MPA-CdSe QDs (quantum dots) and protamine enhanced fluorescent system.

Methods: The image of CdSe QDs was taken on a JEM-2100 transmission electron microscope (JEOL Ltd.). The fluorescence spectrum was recorded on a FluoroMax-4 fluorescence spectrophotometer (Horiba, USA). UV–vis absorption spectrum was recorded using a Shimadzu UV-2450 Spectrophotometer (Tokyo, Japan). A vortex mixer IKA MS3 digital was selected to mix the solution.

Results: Under optimized conditions, the linear response to detect heparin ranges from 0.06 to 14 µg mL-1 with a detection limit of 8 ng mL-1. The approach showed a highly selective response to heparin in the presence of 16 interfered substances.

Conclusion: A simple method for the detection of heparin was developed based on MPA-CdSe QDs and protamine enhanced fluorescent system. The electrostatic effect between MPA-CdSe QDs and protamine resulted in strong fluorescence enhancement from the MPA-CdSe QDs. Moreover, the addition of heparin could cause a significant fluorescence decrease due to the strong affinity of protamine and heparin. Under optimal conditions, this method displayed a low detection limit and good selectivity over other substances.

Keywords: Fluorescence, CdSe quantum dots, electrostatic effect, heparin, fluorescent system, protamine.

[1]
Liu, H.; Zhang, Z.; Linhardt, R.J. Lessons learned from the contamination of heparin. Nat. Prod. Rep., 2009, 26, 313-321.
[2]
Shvarev, A.; Bakker, E. Reversible electrochemical detection of nonelectroactive polyions. J. Am. Chem. Soc., 2003, 125, 11192-11193.
[3]
Jena, B.K.; Raj, C.R. Optical sensing of biomedically important polyionic drugs using nano-sized gold particles. Biosens. Bioelectron., 2008, 23, 1285-1290.
[4]
Cao, R.; Li, B. A simple and sensitive method for visual detection of heparin using positively-charged gold nanoparticles as colorimetric probes. Chem. Commun. , 2011, 47, 2865-2867.
[5]
Wang, Z.X.; Kong, F.Y.; Wang, W.J.; Zhang, R.; Lv, W.X.; Yu, X.H.; Pan, H.C.; Wang, W. “OFF-ON” sensor for detecting heparin based on Hg2+-quenching of photoluminescence nitrogen-rich polymer carbon nanoribbons. Sens. Actuators B ., 2017, 242, 412-417.
[6]
Girolami, B.; Girolami, A. Heparin-induced thrombocytopenia: A review. Semin. Thromb. Hemost., 2006, 32, 803-809.
[7]
Cheng, T.J.; Lin, T.M.; Wu, T.H.; Chang, H.C. Determination of heparin levels in blood with activated partial thromboplastin time by a piezoelectric quartz crystal sensor. Anal. Chim. Acta, 2001, 432, 101-111.
[8]
Langmaier, J.; Samcova, E.; Samec, Z. Potentiometric sensor for heparin polyion: Transient behavior and response mechanism. Anal. Chem., 2007, 79, 2892-2900.
[9]
Patel, R.P.; Narkowicz, C.; Jacobson, G.A. Effective reversed-phase ion pair high-performance liquid chromatography method for the separation and characterization of intact low-molecular-weight heparins. Anal. Biochem., 2009, 387, 113-121.
[10]
Wen, S.; Zheng, F.; Shen, M.; Shi, X. Synthesis of polyethyleneimine-stabilized gold nanoparticles for colorimetric sensing of heparin. Colloid Sur. A, 2013, 419, 80-86.
[11]
Fu, X.; Chen, L.; Li, J. Ultrasensitive colorimetric detection of heparin based on self-assembly of gold nanoparticles on graphene oxide. Analyst , 2012, 137, 3653-3658.
[12]
Fu, X.; Chen, L.; Li, J.; Lin, M.; You, H.; Wang, W. Label-free colorimetric sensor for ultrasensitive detection of heparin based on color quenching of gold nanorods by graphene oxide. Biosens. Bioelectron., 2012, 34, 227-231.
[13]
Ding, S.N.; Chen, J.F.; Xia, J.; Wang, Y.H.; Cosnier, S. Voltammetric detection of heparin based on anion exchange at electropolymeric film of pyrrole-alkylammonium cationic surfactant and MWCNTs composite. Electrochem. Commun., 2013, 34, 339-343.
[14]
Qi, H.; Zhang, L.; Yang, L.; Yu, P.; Mao, L. Anion-Exchange-based amperometric assay for heparin using polyimidazolium as synthetic receptor. Anal. Chem., 2013, 85, 3439-3445.
[15]
Egawa, Y.; Hayashida, R.; Seki, T.; Anzai, J-I. Fluorometric determination of heparin based on self-quenching of fluorescein-labeled protamine. Talanta, 2008, 76, 736-741.
[16]
Sun, W.; Bandmann, H.; Schrader, T. A fluorescent polymeric heparin sensor. Chemistry Eur. J., 2007, 13, 7701-7707.
[17]
Zheng, C.L.; Ji, Z.X.; Zhang, J.; Ding, S.N. A fluorescent sensor to detect sodium dodecyl sulfate based on the glutathione-stabilized gold nanoclusters/poly diallyldimethylammonium chloride system. Analyst , 2014, 139, 3476-3480.
[18]
Sorgi, F.L.; Bhattacharya, S.; Huang, L. Protamine sulfate enhances lipid-mediated gene transfer. Gene Ther., 1997, 4, 961-968.
[19]
Reynolds, F.; Weissleder, R.; Josephson, L. Protamine as an efficient membrane-translocating peptide. Bioconjug. Chem., 2005, 16, 1240-1245.
[20]
Nagai, J.; Komeda, T.; Katagiri, Y.; Yumoto, R.; Takano, M. Characterization of Protamine Uptake by Opossum Kidney Epithelial Cells. Biol. Pharm. Bull., 2013, 36, 1942-1949.
[21]
Algar, W.R.; Susumu, K.; Delehanty, J.B.; Medintz, I.L. Semiconductor quantum dots in bioanalysis: Crossing the valley of death. Anal. Chem., 2011, 83, 8826-8837.
[22]
Smith, A.M.; Duan, H.; Mohs, A.M.; Nie, S. Bioconjugated quantum dots for in vivo molecular and cellular imaging. Adv. Drug Deliv. Rev., 2008, 60, 1226-1240.
[23]
Yan, H.; Wang, H.F. Turn-on Room temperature phosphorescence assay of heparin with tunable sensitivity and detection window based on target-induced self-assembly of polyethyleneimine capped mn-doped zns quantum dots. Anal. Chem., 2011, 83, 8589-8595.
[24]
Chen, Z.; Ren, X.; Meng, X.; Tan, L.; Chen, D.; Tang, F. Quantum dots-based fluorescent probes for turn-on and turn-off sensing of butyrylcholinesterase. Biosens. Bioelectron., 2013, 44, 204-209.
[25]
Liu, S.; Hu, J.; Su, X. Detection of ascorbic acid and folic acid based on water-soluble CuInS2 quantum dots. Analyst , 2012, 137, 4598-4604.
[26]
Liu, S.; Hu, J.; Zhang, H.; Su, X. CuInS2 quantum dots-based fluorescence turn off/on probe for detection of melamine. Talanta, 2012, 101, 368-373.
[27]
Gao, X.; Liu, X.; Lin, Z.; Liu, S.; Su, X. CuInS2 quantum dots as a near-infrared fluorescent probe for detecting thrombin in human serum. Analyst , 2012, 137, 5620-5624.
[28]
Gao, X.; Tang, G.; Li, Y.; Su, X. A novel optical nanoprobe for trypsin detection and inhibitor screening based on Mn-doped ZnSe quantum dots. Anal. Chim. Acta, 2012, 743, 131-136.
[29]
Cao, Y.; Shi, S.; Wang, L.; Yao, J.; Yao, T. Ultrasensitive fluorescence detection of heparin based on quantum dots and a functional ruthenium polypyridyl complex. Biosens. Bioelectron., 2014, 55, 174-179.
[30]
Liu, Z.; Ma, Q.; Wang, X.; Lin, Z.; Zhang, H.; Liu, L.; Su, X. A novel fluorescent nanosensor for detection of heparin and heparinase based on CuInS2 quantum dots. Biosens. Bioelectron., 2014, 54, 617-622.
[31]
Luo, J.D.; Xie, Z.L.; Lam, J.W.Y.; Cheng, L.; Chen, H.Y.; Qiu, C.F.; Kwok, H.S.; Zhan, X.W.; Liu, Y.Q.; Zhu, D.B.; Tang, B.Z. Aggregation-induced emission of 1-methyl-1,2,3,4,5-pentaphenylsilole. Chem. Commun. , 2001, 18, 1740-1741.
[32]
Lim, S.J.; An, B.K.; Jung, S.D.; Chung, M.A.; Park, S.Y. Photoswitchable organic nanoparticles and a polymer film employing multifunctional molecules with enhanced fluorescence emission and bistable photochromism. Angew. Chem. Int. Ed., 2004, 43, 6346-6350.
[33]
Deans, R.; Kim, J.; Machacek, M.R.; Swager, T.M. A poly (p-phenyleneethynylene) with a highly emissive aggregated phase. J. Am. Chem. Soc., 2000, 122, 8565-8566.
[34]
Qian, Y.; Li, S.; Zhang, G.; Wang, Q.; Wang, S.; Xu, H.; Li, C.; Li, Y.; Yang, G. Aggregation-induced emission enhancement of 2-(2 '-hydroxyphenyl)benzothiazole-based excited-state intramolecular proton-transfer compounds. J. Phys. Chem. B, 2007, 111, 5861-5868.
[35]
Shimizu, M.; Takeda, Y.; Higashi, M.; Hiyama, T. 1,4-Bis(alkenyl)-2,5-dipiperidinobenzenes: Minimal fluorophores exhibiting highly efficient emission in the solid state. Angew. Chem. Int. Ed., 2009, 48, 3653-3656.
[36]
Chen, X.T.; Xiang, Y.; Li, N.; Song, P.S.; Tong, A.J. Fluorescence turn-on detection of protamine based on aggregation-induced emission enhancement characteristics of 4-(6 '-carboxyl)hexyloxysalicylaldehyde azine. Analyst , 2010, 135, 1098-1105.
[37]
Peng, L.; Wang, M.; Zhang, G.; Zhang, D.; Zhu, D. A Fluorescence turn-on detection of cyanide in aqueous solution based on the aggregation-induced emission. Org. Lett., 2009, 11, 1943-1946.
[38]
Wang, M.; Gu, X.; Zhang, G.; Zhang, D.; Zhu, D. Convenient and Continuous fluorometric assay method for acetylcholinesterase and inhibitor screening based on the aggregation-induced emission. Anal. Chem., 2009, 81, 4444-4449.
[39]
Wang, M.; Zhang, D.; Zhang, G.; Tang, Y.; Wang, S.; Zhu, D. Fluorescence turn-on detection of DNA and label-free fluorescence nuclease assay based on the aggregation-induced emission of silole. Anal. Chem., 2008, 80, 6443-6448.
[40]
Chen, X.; Hutchison, J.L.; Dobson, P.J.; Wakefield, G. Highly luminescent monodisperse CdSe nanoparticles synthesized in aqueous solution. J. Mater. Sci., 2009, 44, 285-292.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 15
ISSUE: 5
Year: 2019
Page: [599 - 604]
Pages: 6
DOI: 10.2174/1573411014666180330160743
Price: $65

Article Metrics

PDF: 42
HTML: 2

Special-new-year-discount