Journal of Nanoparticle Research

, Volume 13, Issue 9, pp 4075–4083 | Cite as

Phosphorylcholine functionalized dendrimers for the formation of highly stable and reactive gold nanoparticles and their glucose conjugation for biosensing

  • Lan Jia
  • Li-Ping Lv
  • Jian-Ping Xu
  • Jian Ji
Research Paper


Phosphorylcholine (PC)-functionalized poly(amido amine) (PAMAM) dendrimers were prepared and used as both reducing and stabilizing agents for synthesis of highly stable and reactive gold nanoparticles (Au NPs). Biomimetic PC-functionalized PAMAM dendrimers-stabilized gold nanoparticles (Au DSNPs) were formed by simply mixing the PC modified amine-terminated fifth-generation PAMAM dendrimers (G5-PC) with AuCl4 ions by controlling the pH, no additional reducing agents or other stabilizers were needed. The obtained Au DSNPs were shown to be spherical, with particle diameters ranging from 5 to 12 nm, the sizes and growth kinetics of Au DSNPs could be tuned by changing the pH and the initial molar ratio of dendrimers to gold as indicated by transmission electron microscopy (TEM) and UV–Vis data. The prepared Au DSNPs showed excellent stability including: (1) stable at wide pH (7–13) values; (2) stable at high salt concentrations up to 2 M NaCl; (3) non-specific protein adsorption resistance. More importantly, surface functionalization could be performed by introducing desired functional groups onto the remained reactive amine groups. This was exemplified by the glucose conjugation. The glucose conjugated Au DSNPs showed bio-specific interaction with Concanavalin A (Con A), which induced aggregation of the Au NPs. Colorimetric detection of Con A based on the plasmon resonance of the glucose conjugated Au DSNPs was realized. A limit of detection (LOD) for Con A was 0.6 μM, based on a signal-to-noise ratio (S/N) of 3. These findings demonstrated that the PC modified Au DSNPs could potentially serve as a versatile nano-platform for the biomedical applications.


Biomimetic Poly (amido amine) Biosensors Stability Colorimetric Gold nanoparticles Nanomedicine 



This research was financially supported by Natural Science Foundation of China (NSFC-20774082, 50703036, 50830106), National Science Fund for Distinguished Young Scholars (51025312), Zhejiang Provincial Natural Science Foundation of China (Y4080024, Y4080250), Ph.D. Programs Foundation of Ministry of Education (No. 20070335024) and Qianjiang Excellence Project of Zhejiang Province (2009R10051).

Supplementary material

11051_2011_351_MOESM1_ESM.doc (1.6 mb)
Supplementary material 1 (DOC 1685 kb)


  1. Banerjee SS, Chen DH (2007) Glucose-grafted gum arabic modified magnetic nanoparticles: preparation and specific interaction with concanavalin A. Chem Mater 19:3667–3672CrossRefGoogle Scholar
  2. Cao YWC, Jin RC, Mirkin CA (2002) Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection. Science 297:1536–1540CrossRefGoogle Scholar
  3. Chen SF, Zheng J, Li LY, Jiang SY (2005) Strong resistance of phosphorylcholine self-assembled monolayers to protein adsorption: insights into nonfouling properties of zwitterionic materials. J Am Chem Soc 127:14473–14478CrossRefGoogle Scholar
  4. Duchesne L, Gentili D, Franchini MC, Fernig DG (2008) Robust ligand shells for biological applications of gold nanoparticles. Langmuir 24:13572–13580CrossRefGoogle Scholar
  5. Eck W, Craig G, Sigdel A, Ritter G, Old LJ, Tang L, Brennan MF, Allen PJ, Mason MD (2008) PEGylated gold nanoparticles conjugated to monoclonal F19 antibodies as targeted labeling agents for human pancreatic carcinoma tissue. ACSNano 2:2263–2272Google Scholar
  6. Gill R, Zayats M, Willner I (2008) Semiconductor quantum dots for bioanalysis. Angew Chem Int Ed 47:7602–7625CrossRefGoogle Scholar
  7. Grohn F, Kim G, Bauer BJ, Amis EJ (2001) Nanoparticle formation within dendrimer-containing polymer networks: route to new organic-inorganic hybrid materials. Macromolecules 34:2179–2185CrossRefGoogle Scholar
  8. Haba Y, Kojima C, Harada A, Ura T, Horinaka H, Kono K (2007) Preparation of poly (ethylene glycol)-modified poly (amido amine) dendrimers encapsulating gold nanoparticles and their heat-generating ability. Langmuir 23:5243–5246CrossRefGoogle Scholar
  9. Han G, You CC, Kim BJ, Turingan RS, Forbes NS, Martin CT, Rotello VM (2006) Light-regulated release of DNA and its delivery to nuclei by means of photolabile gold nanoparticles. Angew Chem Int Ed 45:3165–3169CrossRefGoogle Scholar
  10. Huang CC, Huang YF, Cao ZH, Tan WH, Chang HT (2005) Aptamer-modified gold nanoparticles for colorimetric determination of platelet-derived growth factors and their receptors. Anal Chem 77:5735–5741CrossRefGoogle Scholar
  11. Ishihara K, Ueda T, Nakabayashi N (1990) Preparation of phospholipid polymers and their properties as polymer hydrogel membranes. Polym J 22:355–360CrossRefGoogle Scholar
  12. Ishihara K, Ziats NP, Tierney BP, Nakabayashi N (1991) Protein adsorption from human plasma is reduced on phospholipid polymers. J Biomed Mater Res 25:1397–1407CrossRefGoogle Scholar
  13. Ishihara K, Iwasaki Y, Nakabayashi N (1998) Novel biomedical polymers for regulating serious biological reactions. Mater Sci Eng C Biomimetic Supramol Syst 6:253–259CrossRefGoogle Scholar
  14. Iwasaki Y, Ishihara K (2005) Phosphorylcholine-containing polymers for biomedical applications. Anal Bioanal Chem 381:534–546CrossRefGoogle Scholar
  15. Ji XH, Song XN, Li J, Bai YB, Yang WS, Peng XG (2007) Size control of gold nanocrystals in citrate reduction: the third role of citrate. J Am Chem Soc 129:13939–13948CrossRefGoogle Scholar
  16. Jin Q, Xu JP, Ji J, Shen JC (2008) Zwitterionic phosphorylcholine as a better ligand for stabilizing large biocompatible gold nanoparticles. Chem Commun pp 3058–3060Google Scholar
  17. Jin Q, Liu XS, Xu JP, Ji J, Shen JC (2009) Zwitterionic phosphorylcholine-protected water-soluble Ag nanoparticles. Sci China Ser B Chem 52:64–68CrossRefGoogle Scholar
  18. Kanaras AG, Wang ZX, Hussain I, Brust M, Cosstick R, Bates AD (2007) Site-specific ligation of DNA-modified gold nanoparticles activated by the restriction enzyme StyI. Small 3:67–70CrossRefGoogle Scholar
  19. Kim YG, Oh SK, Crooks RM (2004) Preparation and characterization of 1–2 nm dendrimer-encapsulated gold nanoparticles having very narrow size distributions. Chem Mater 16:167–172CrossRefGoogle Scholar
  20. Lee S, Prez-Luna VH (2005) Dextran-gold nanoparticle hybrid material for biomolecule immobilization and detection. Anal Chem 77:7204–7211CrossRefGoogle Scholar
  21. Li D, Wieckowska A, Willner I (2008) Optical analysis of Hg2+ ions by oligonucleotide-gold-nanoparticle hybrids and DNA-based machines. Angew Chem Int Ed 47:3927–3931CrossRefGoogle Scholar
  22. Licciardi M, Tang Y, Billingham NC, Armes SP, Lewis AL (2005) Synthesis of novel folic acid-functionalized biocompatible block copolymers by atom transfer radical polymerization for gene delivery and encapsulation of hydrophobic drugs. Biomacromolecules 6:1085–1096CrossRefGoogle Scholar
  23. Liu JW, Lu Y (2006) Fast colorimetric sensing of adenosine and cocaine based on a general sensor design involving aptamers and nanoparticles. Angew Chem Int Ed 45:90–94CrossRefGoogle Scholar
  24. Liu CW, Hsieh YT, Huang CC, Lina ZH, Chang HT (2008) Detection of mercury(II) based on Hg2+-DNA complexes inducing the aggregation of gold nanoparticles. Chem Commun pp 2242–2244Google Scholar
  25. Lu C, Zu YB (2007) Specific detection of cysteine and homocysteine: recognizing one-methylene difference using fluorosurfactant-capped gold nanoparticles. Chem Commun 37:3871–3873CrossRefGoogle Scholar
  26. Luk YY, Kato M, Mrksich M (2000) Self-assembled monolayers of alkanethiolates presenting mannitol groups are inert to protein adsorption and cell attachment. Langmuir 16:9604–9608CrossRefGoogle Scholar
  27. Maxwell DJ, Taylor JR, Nie SM (2002) Self-assembled nanoparticle probes for recognition and detection of biomolecules. J Am Chem Soc 124:9606–9612CrossRefGoogle Scholar
  28. Ostuni E, Chapman RG, Holmlin RK, Takayama S, Whitesides GM (2001) A survey of structure-property relationships of surfaces that resist the adsorption of protein. Langmuir 17:5605–5620CrossRefGoogle Scholar
  29. Paciotti GF, Kingston DGI, Tamarkin L (2006) Colloidal gold nanoparticles: a novel nanoparticle platform for developing multifunctional tumor-targeted drug delivery vectors. Drug Dev Res 67:47–54CrossRefGoogle Scholar
  30. Rose SF, Lewis AL, Hanlon GW, Lioyd AW (2004) Biological responses to cationically materials charged phosphorylcholine-based in vitro. Biomaterials 25:5125–5135CrossRefGoogle Scholar
  31. Rosi NL, Mirkin CA (2005) Nanostructures in biodiagnostics. Chem Rev 105:1547–1562CrossRefGoogle Scholar
  32. Ruiz L, Hilborn JG, Leonard D, Mathieu HJ (1998) Synthesis, structure and surface dynamics of phosphorylcholine functional biomimicking polymers. Biomaterials 19:987–998CrossRefGoogle Scholar
  33. Sardar R, Park JW, Shumaker-Parry JS (2007) Polymer-induced synthesis of stable gold and silver nanoparticles and subsequent ligand exchange in water. Langmuir 23:11883–11889CrossRefGoogle Scholar
  34. Schofield CL, Haines AH, Field RA, Russell DA (2006) Silver and gold glyconanoparticles for colorimetric bioassays. Langmuir 22(15):6707–6711CrossRefGoogle Scholar
  35. Schofield CL, Field RA, Russell DA (2007) Glyconanoparticles for the colorimetric detection of cholera toxin. Anal Chem 79:1356–1361CrossRefGoogle Scholar
  36. Shi XY, Sun K, Baker JR (2008) Spontaneous formation of functionalized dendrimer-stabilized gold nanoparticles. J Phys Chem C 112:8158–8251Google Scholar
  37. Sun XP, Luo YL (2005) Size-controlled synthesis of dendrimer-protected gold nanoparticles by microwave radiation. Mater Lett 59:4048–4050CrossRefGoogle Scholar
  38. Sun XP, Xiue Jiang, Dong SJ, Wang EK (2003) One-step synthesis and size control of dendrimer-protected gold nanoparticles: a heat-treatment-based strategy. Macromol Rapid Commun 24:1024–1028CrossRefGoogle Scholar
  39. Tomalia DA, Naylor AM, Goddard WA (1990) Starbust dendrimers-molecular-level control of size, shape, surface-chemistry, topology, and flexibility from atoms to macroscopic matter. Angew Chem Int Ed Eng 29:138–175CrossRefGoogle Scholar
  40. Tsai CS, Yu TB, Chen CT (2005) Gold nanoparticle-based competitive colorimetric assay for detection of protein-protein interactions. Chem Commun 34:4273–4275CrossRefGoogle Scholar
  41. Wang ZD, Lee JH, Lu Y (2008) Label-free colorimetric detection of lead ions with a nanomolar detection limit and tunable dynamic range by using gold nanoparticles and DNAzyme. Adv Mater 20:3263–3267CrossRefGoogle Scholar
  42. Wang S, Qian K, Bi XZ, Huang WX (2009) Influence of speciation of aqueous HAuCl4 on the synthesis, structure, and property of Au colloids. J Phys Chem C 113:6505–6510CrossRefGoogle Scholar
  43. Woehrle GH, Brown LO, Hutchison JE (2005) Thiol-functionalized, 1.5-nm gold nanoparticles through ligand exchange reactions: scope and mechanism of ligand exchange. J Am Chem Soc 127:2172–2183CrossRefGoogle Scholar
  44. Xu JP, Ji J, Chen WD, Fan DZ, Sun FY, Shen JC (2004) Phospholipid based polymer as drug release coating for cardiovascular device. Eur Polym J 40:291–298CrossRefGoogle Scholar
  45. Yonzon CR, Jeoung E, Zou S, Schatz GC, Mrksich M, Van Duyne RP (2004) A comparative analysis of localized and propagating surface plasmon resonance sensors: the binding of concanavalin a to a monosaccharide functionalized self-assembled monolayer. J Am Chem Soc 126:12669–12676CrossRefGoogle Scholar
  46. Yuan JJ, Schmid A, Armes SP, Lewis AL (2006) Facile synthesis of highly biocompatible poly (2-(methacryloyloxy-ethyl phosphorylcholine)-coated gold nanoparticles in aqueous solution. Langmuir 22:11022–11027CrossRefGoogle Scholar
  47. Zhang J, Wang LH, Pan D, Song SP, Boey FYC, Zhang H, Fan CH (2008) Visual cocaine detection with gold nanoparticles and rationally engineered aptamer structures. Small 4:1196–1200CrossRefGoogle Scholar
  48. Zhang GD, Yang Z, Lu W, Zhang R, Huang Q, Tian M, Li L, Liang D, Li C (2009) Influence of anchoring ligands and particle size on the colloidal stability and in vivo biodistribution of polyethylene glycol-coated gold nanoparticles in tumor-xenografted mice. Biomaterials 30:1928–1936CrossRefGoogle Scholar
  49. Zhao WA, Lam JCF, Chiuman W, Brook MA, Li YF (2008) Enzymatic cleavage of nucleic acids on gold nanoparticles: a generic platform for facile colorimetric biosensors. Small 4:810–816CrossRefGoogle Scholar
  50. Zheng M, Huang XY (2004) Nanoparticles comprising a mixed monolayer for specific bindings with biomolecules. J Am Chem Soc 126:12047–12054CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  1. 1.Department of Polymer Science and Engineering, MOE Key Laboratory of Macromolecular Synthesis and FunctionalizationZhejiang UniversityHangzhouChina

Personalised recommendations