Novel nanoarchitecture of arginine-glycine-aspartate conjugated gold nanoparticles: a sensitive and selective platform for detecting arachidonic acid

  • Nana Zhang
  • Jian Li
  • Panpan Zhang
  • Xiaodi YangEmail author
  • Chong SunEmail author
Research Paper


A novel electrochemical approach for determination of arachidonic acid (ARA) was developed based on the linear arginine-glycine-aspartic-Au (RGD-Au) nanomaterial modified on glassy carbon electrode (GCE). The prepared material was characterized by transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), ultraviolet-visible spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The electrochemical signal was obtained from the reduction of 1,4-naphthoquinone and ARA served as a proton source. Under the optimum experimental conditions, the RGD-Au-based electrode was used to analyze ARA. Meanwhile, the electrochemical characteristics were also studied by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and linear sweep voltammetry (LSV). The sensor showed a wider linear range from 0.5 to 100 μM and the linear fitting equation was Ip (μA) = 0.0721 c + 2.4583 (R2 = 0.9987) with a detection limit of 80 nM. The application of the sensor in real samples was tested and compared with that of LC-MS/MS. This sensor would be a promising platform for detection of ARA in blood plasma.

Graphical abstract


RGD-Au nanomaterial Arachidonic acid 1,4-Naphthoquinone Electrochemical sensor 


Funding information

This study was supported by the National Natural Science Foundation of China (21575067, 31601405), the Natural Science Foundation Program of Jiangsu Province (BK20160591), and the Research Funding of Jiangsu Academy of Agricultural Sciences (6111681).

Compliance with ethical standards

The study was approved by the ethic committee of Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Nanjing Normal University, and all the experiments were carried out in strict accordance with the ethical standards.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2019_2092_MOESM1_ESM.pdf (313 kb)
ESM 1 (PDF 312 kb)


  1. 1.
    Ogawa S, Tomaru K, Matsumoto N, Watanabe S, Higashi T. LC/ESI-MS/MS method for determination of salivary eicosapentaenoic acid concentration to arachidonic acid concentration ratio. Biomed Chromatogr. 2016;30(1):29–34.CrossRefGoogle Scholar
  2. 2.
    Navratil AR, Shchepinov MS, Dennis EA. Lipidomics reveals dramatic physiological kinetic isotope effects during the enzymatic oxygenation of polyunsaturated fatty acids ex vivo. J Am Chem Soc. 2018;140(1):235–43.CrossRefGoogle Scholar
  3. 3.
    Yu Y, Li T, Wu N, Ren L, Jiang L, Ji X, et al. Mechanism of arachidonic acid accumulation during aging in Mortierella alpina: a large-scale label-free comparative proteomics study. J Agric Food Chem. 2016;64(47):9124–34.CrossRefGoogle Scholar
  4. 4.
    Schneider C, Boeglin WE, Yin HY, Stec DF, Voehler M. Convergent oxygenation of arachidonic acid by 5-lipoxygenase and cyclooxygenase-2. J Am Chem Soc. 2006;128(3):720–1.CrossRefGoogle Scholar
  5. 5.
    Peng S, Okeley NM, Tsai AL, Wu G, Kulmacz RJ, van der Donk WA. Synthesis of isotopically labeled arachidonic acids to probe the reaction mechanism of prostaglandin H synthase. J Am Chem Soc. 2002;124(36):10785–96.CrossRefGoogle Scholar
  6. 6.
    Wang W, Qin S, Li L, Chen X, Wang Q, Wei J. An optimized high throughput clean-up method using mixed-mode SPE plate for the analysis of free arachidonic acid in plasma by LC-MS/MS. Int J Anal Chem. 2015;2015:374819.Google Scholar
  7. 7.
    Harris WS, Mozaffarian D, Rimm E, Kris-Etherton P, Rudel LL, Appel LJ, et al. Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention. Circulation. 2009;119(6):902–7.CrossRefGoogle Scholar
  8. 8.
    Devlin AM, Chau CMY, Dyer R, Matheson J, McCarthy D, Yurko-Mauro K et al. Developmental outcomes at 24 months of age in toddlers supplemented with arachidonic acid and docosahexaenoic acid: results of a double blind randomized, controlled trial. Nutrients. 2017;9(9):975.Google Scholar
  9. 9.
    Waddington EI, Croft KD, Sienuarine K, Latham B, Puddey IB. Fatty acid oxidation products in human atherosclerotic plaque: an analysis of clinical and histopathological correlates. Atherosclerosis. 2003;167(1):111–20.CrossRefGoogle Scholar
  10. 10.
    Giovannozzi AM, Ferrero VE, Pennecchi F, Sadeghi SJ, Gilardi G, Rossi AM. P450-based porous silicon biosensor for arachidonic acid detection. Biosens Bioelectron. 2011;28(1):320–5.CrossRefGoogle Scholar
  11. 11.
    Sanchez-Mejia RO, Mucke L. Phospholipase A2 and arachidonic acid in Alzheimer’s disease. Biochim Biophys Acta. 2010;1801(8):784–90.CrossRefGoogle Scholar
  12. 12.
    Blank I, Lin JM, Vera FA, Welti DH, Fay LB. Identification of potent odorants formed by autoxidation of arachidonic acid: Structure elucidation and synthesis of (E,Z,Z)-2,4,7-tridecatrienal. J Agric Food Chem. 2001;49(6):2959–65.CrossRefGoogle Scholar
  13. 13.
    Ito J, Mizuochi S, Nakagawa K, Kato S, Miyazawa T. Tandem mass spectrometry analysis of linoleic and arachidonic acid hydroperoxides via promotion of alkali metal adduct formation. Anal Chem. 2015;87(9):4980–7.CrossRefGoogle Scholar
  14. 14.
    Shinde DD, Kim KB, Oh KS, Abdalla N, Liu KH, Bae SK, et al. LC-MS/MS for the simultaneous analysis of arachidonic acid and 32 related metabolites in human plasma: basal plasma concentrations and aspirin-induced changes of eicosanoids. J Chromatogr B. 2012;911:113–21.CrossRefGoogle Scholar
  15. 15.
    Yang M, Nie S, Li J, Xie M, Xiong H, Deng Z, et al. Near-infrared spectroscopy and partial least-squares regression for determination of arachidonic acid in powdered oil. Lipids. 2010;45(6):559–65.CrossRefGoogle Scholar
  16. 16.
    Ilyina AD, Hernandez JLM, Badillo CE, Maldonado MGS, Galindo SC, Gonzalez MH, et al. Determination of arachidonic acid based on the prostaglandin H synthase catalyzed reaction. Appl Biochemi Biotech. 2000;88(1–3):33–44.CrossRefGoogle Scholar
  17. 17.
    Quinlivan VH, Wilson MH, Ruzicka J, Farber SA. An HPLC-CAD/fluorescence lipidomics platform using fluorescent fatty acids as metabolic tracers. J Lipid Res. 2017;58(5):1008–20.CrossRefGoogle Scholar
  18. 18.
    Kimmel DW, LeBlanc G, Meschievitz ME, Cliffel DE. Electrochemical sensors and biosensors. Anal Chem. 2012;84(2):685–707.CrossRefGoogle Scholar
  19. 19.
    Kuyumcu SE. Electrochemical determination of N-acetyl cysteine in the presence of acetaminophen at multi-walled carbon nanotubes and Nafion modified sensor. Sens Actuators B Chem. 2019;282:500–6.CrossRefGoogle Scholar
  20. 20.
    Aydindogan E, Guler Celik E, Odaci Demirkol D, Yamada S, Endo T, Timur S, et al. Surface modification with a catechol-bearing polypeptide and sensing applications. Biomacromolecules. 2018;19(7):3067–76.CrossRefGoogle Scholar
  21. 21.
    Bozokalfa G, Akbulut H, Demir B, Guler E, Gumus ZP, Odaci Demirkol D, et al. Polypeptide functional surface for the aptamer immobilization: electrochemical cocaine biosensing. Anal Chem. 2016;88(7):4161–7.CrossRefGoogle Scholar
  22. 22.
    Guo H, Lee C, Shah M, Janga SR, Edman MC, Klinngam W, et al. A novel elastin-like polypeptide drug carrier for cyclosporine A improves tear flow in a mouse model of Sjogren’s syndrome. J Control Release. 2018;292:183–95.CrossRefGoogle Scholar
  23. 23.
    Jang LK, Kim S, Seo J, Young LJ. Facile and controllable electrochemical fabrication of cell-adhesive polypyrrole electrodes using pyrrole-RGD peptides. Biofabrication. 2017;9(4):045007.CrossRefGoogle Scholar
  24. 24.
    Guo CX, Ng SR, Khoo SY, Zheng XT, Chen P, Li CM. RGD-peptide functionalized graphene biomimetic live-cell sensor for real-time detection of nitric oxide molecules. ACS Nano. 2012;6(8):6944–51.CrossRefGoogle Scholar
  25. 25.
    Polo E, Nitka TT, Neubert E, Erpenbeck L, Vukovic L, Kruss S. Control of integrin affinity by confining RGD peptides on fluorescent carbon nanotubes. ACS Appl Mater Interfaces. 2018;10(21):17693–703.CrossRefGoogle Scholar
  26. 26.
    Dong J, Wang K, Sun L, Sun B, Yang M, Chen H, et al. Application of graphene quantum dots for simultaneous fluorescence imaging and tumor-targeted drug delivery. Sens Actuators B Chem. 2018;256:616–23.CrossRefGoogle Scholar
  27. 27.
    Yang J, Luo Y, Xu Y, Li J, Zhang Z, Wang H, et al. Conjugation of iron oxide nanoparticles with RGD-modified dendrimers for targeted tumor MR imaging. ACS Appl Mater Interfaces. 2015;7(9):5420–8.CrossRefGoogle Scholar
  28. 28.
    Yang X, Zhao L, Zheng L, Xu M, Cai X. Polyglycerol grafting and RGD peptide conjugation on MnO nanoclusters for enhanced colloidal stability, selective cellular uptake and cytotoxicity. Colloids Surf B. 2018;163:167–74.CrossRefGoogle Scholar
  29. 29.
    Gallo J, Alam IS, Lavdas I, Wylezinska-Arridge M, Aboagye EO, Long NJ. RGD-targeted MnO nanoparticles as T1contrast agents for cancer imaging—the effect of PEG length in vivo. J Mater Chem B. 2014;2(7):868–76.CrossRefGoogle Scholar
  30. 30.
    Yang L, Li N, Wang K, Hai X, Liu J, Dang F. A novel peptide/Fe3O4@SiO2-Au nanocomposite-based fluorescence biosensor for the highly selective and sensitive detection of prostate-specific antigen. Talanta. 2018;179:531–7.CrossRefGoogle Scholar
  31. 31.
    Hu KC, Lan DX, Li XM, Zhang SS. Electrochemical DNA biosensor based on nanoporous gold electrode and multifunctional encoded DNA-Au bio bar codes. Anal Chem. 2008;80(23):9124–30.CrossRefGoogle Scholar
  32. 32.
    Yu AM, Liang ZJ, Cho J, Caruso F. Nanostructured electrochemical sensor based on dense gold nanoparticle films. Nano Lett. 2003;3(9):1203–7.CrossRefGoogle Scholar
  33. 33.
    Yin HQ, Bi FL, Gan F. Rapid synthesis of cyclic RGD conjugated gold nanoclusters for targeting and fluorescence imaging of melanoma A375 cells. Bioconjug Chem. 2015;26(2):243–9.CrossRefGoogle Scholar
  34. 34.
    Zong J, Cobb SL, Cameron NR. Short elastin-like peptide-functionalized gold nanoparticles that are temperature responsive under near-physiological conditions. J Mater Chem B. 2018;6(41):6667–74.CrossRefGoogle Scholar
  35. 35.
    Xiong Y, Gao W, Xia F, Sun Y, Sun L, Wang L, et al. Peptide-gold nanoparticle hybrids as promising anti-inflammatory nanotherapeutics for acute lung injury: in vivo efficacy, biodistribution, and clearance. Adv Healthc Mater. 2018;7(19):e1800510.CrossRefGoogle Scholar
  36. 36.
    Zhao W, Gonzaga F, Li Y, Brook MA. Highly stabilized nucleotide-capped small gold nanoparticles with tunable size. Adv Mater. 2007;19(13):1766–71.CrossRefGoogle Scholar
  37. 37.
    Yin HQ, Mai DS, Gan F, Chen XJ. One-step synthesis of linear and cyclic RGD conjugated gold nanoparticles for tumour targeting and imaging. RSC Adv. 2014;4(18):9078.CrossRefGoogle Scholar
  38. 38.
    Teengam P, Siangproh W, Tuantranont A, Vilaivan T, Chailapakul O, Henry CS. Electrochemical impedance-based DNA sensor using pyrrolidinyl peptide nucleic acids for tuberculosis detection. Anal Chim Acta. 2018;1044:102–9.CrossRefGoogle Scholar
  39. 39.
    Rueda-García D, Dubal DP, Huguenin F, Gómez-Romero P. Hurdles to organic quinone flow cells. Electrode passivation by quinone reduction in acetonitrile Li electrolytes. J Power Sources. 2017;350:9–17.CrossRefGoogle Scholar
  40. 40.
    Taran O. Electron transfer between electrically conductive minerals and quinones. Front Chem. 2017;5.Google Scholar
  41. 41.
    Kotani A, Watanabe M, Yamamoto K, Kusu F, Hakamata H. Determination of eicosapentaenoic, docosahexaenoic, and arachidonic acids in human plasma by high-performance liquid chromatography with electrochemical detection. Anal Sci. 2016;32(9):1011–4.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Environmental Science Research Institute, Jiangsu Collaborative Innovation Center of Biomedical Functional MaterialsNanjing Normal UniversityNanjingChina
  2. 2.Neurosurgery DepartmentAffiliated Hospital of Nanjing University of Traditional Chinese MedicineNanjingChina
  3. 3.Institute of Agricultural Products ProcessingJiangsu Academy of Agricultural SciencesNanjingChina

Personalised recommendations