PAMAM dendrimer-coated iron oxide nanoparticles: synthesis and characterization of different generations

  • Rouhollah KhodadustEmail author
  • Gozde Unsoy
  • Serap Yalcın
  • Gungor Gunduz
  • Ufuk GunduzEmail author
Research Paper


This study focuses on the synthesis and characterization of different generations (G0–G7) of polyamidoamine (PAMAM) dendrimer-coated magnetic nanoparticles (DcMNPs). In this study, superparamagnetic iron oxide nanoparticles were synthesized by co-precipitation method. The synthesized nanoparticles were modified with aminopropyltrimethoxysilane for dendrimer coating. Aminosilane-modified MNPs were coated with PAMAM dendrimer. The characterization of synthesized nanoparticles was performed by X-ray diffraction, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), dynamic light scattering, and vibrating sample magnetometry (VSM) analyses. TEM images demonstrated that the DcMNPs have monodisperse size distribution with an average particle diameter of 16 ± 5 nm. DcMNPs were found to be superparamagnetic through VSM analysis. The synthesis, aminosilane modification, and dendrimer coating of iron oxide nanoparticles were validated by FTIR and XPS analyses. Cellular internalization of nanoparticles was studied by inverted light scattering microscopy, and cytotoxicity was determined by XTT analysis. Results demonstrated that the synthesized DcMNPs, with their functional groups, symmetry perfection, size distribution, improved magnetic properties, and nontoxic characteristics could be suitable nanocarriers for targeted cancer therapy upon loading with various anticancer agents.


Iron Oxide (Fe3O4Dendrimer Magnetic nanoparticle Cancer therapy 



Magnetic nanoparticles, magnetite, Fe3O4


Polyamidoamine (PAMAM) dendrimer-coated magnetic nanoparticles (DcMNPs)




X-ray diffraction


Fourier transform infrared spectroscopy


Transmission electron microscopy


Dynamic light scattering


Thermal gravimetric analysis


Vibrating sample magnetometry


Saturated magnetization



The support of Asst. Prof. Dr. Bora Mavis for FTIR, as well as financial support by TÜBİTAK-2215 (PhD Fellowship for foreign citizens), is gratefully acknowledged.


  1. Acharya S, Dilnawaz F, Sahoo SK (2009) Targeted epidermal growth factor receptor nanoparticle bioconjugates for breast cancer therapy. Biomaterials 30:5737–5750CrossRefGoogle Scholar
  2. Arias JL, Gallardo V, Gómez-Lopera SA, Plaza RC, Delgado AV (2001) Synthesis and characterization of poly(ethyl-2-cyanosilane) nanoparticles with a magnetic core. J Control Release 13:309–321CrossRefGoogle Scholar
  3. Bazylinski DA (1996) Controlled biomineralization of magnetic minerals by magnetotactic bacteria. Chem Geol 132:191–198CrossRefGoogle Scholar
  4. Boas U, Karlsson AJ, de Waal BF, Meijer EW (2001) Synthesis and properties of new thiourea-functionalized poly(propylene imine) dendrimers and their role as hosts for urea functionalized guests. J Org Chem 66(6):2136–2145CrossRefGoogle Scholar
  5. Chou CM, Lien HL (2011) Dendrimer-conjugated magnetic nanoparticles for removal of zinc (II) from aqueous solutions. J Nanopart Res 13(5):2099–2107CrossRefGoogle Scholar
  6. Du X, Poltorak A, Wei Y, Beutler B (2000) Three novel mammalian toll like receptors: gene structure, expression, and evolution. Eur Cytokine Netw 11(3):362–371Google Scholar
  7. Duncan R, Izzo L (2005) Dendrimer biocompatibility and toxicity. Adv Drug Deliv Rev 57:2215–2237CrossRefGoogle Scholar
  8. Durmus Z, Kavas H, Toprak MS, Baykal A, Altınçekiç TG, Aslan A, Bozkurt A, Coşgun S (2009) l-lysine coated iron oxide nanoparticles: synthesis, structual and conductivity characterization. J Alloy Compd 484(1–2):371–376CrossRefGoogle Scholar
  9. Esfand R, Tomalia DA (2001) Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications. Drug Discov Today 6:427–436CrossRefGoogle Scholar
  10. Gao F, Pan BF, Zheng WM, Ao LM, Gu HC (2005) Study of streptavidin coated onto PAMAM dendrimer modified magnetite nanoparticles. J Magn Magn Mater 293:48–54CrossRefGoogle Scholar
  11. Gupta AK, Wells S (2004) Surface-modified superparamagnetic nanoparticles for drug delivery: preparation, characterization, and cytotoxicity studies. IEEE Trans Nano Biosci 3:66–73CrossRefGoogle Scholar
  12. Gurdag S, Khandare J, Stapels S, Matherly LH, Kannan RM (2006) Activity of dendrimer-methotrexate conjugates on methotrexate-sensitive and -resistant cell lines. Bioconjug Chem 17:275–283CrossRefGoogle Scholar
  13. Hansson GK, Edfeldt K (2005) Toll to be paid at the gateway to the vessel wall. Arterioscler Thromb Vasc Biol 25(6):1085–1087CrossRefGoogle Scholar
  14. Hoa LTM, Dung TT, Danh TM, Duc NH, Chien DM (2009) Preparation and characterization of magnetic nanoparticles coated with polyethylene glycol. J Phys 187(1):012048. doi: 10.1088/1742-6596/187/1/012048 Google Scholar
  15. Hong S, Bielinska AU, Mecke A, Keszler B, Beals JL, Shi X, Balogh L, Orr BG, Baker JR Jr, Banaszak-Holl MM (2004) Interaction of poly(amidoamine) dendrimers with supported lipid bilayers and cells: hole formation and the relation to transport. Bioconjug Chem 15:774–782CrossRefGoogle Scholar
  16. Julian JM, Anderson DG, Brandau AH, McGinn JR, Millon AM (1991) In: Brezinski DR (ed) An infrared spectroscopy atlas for the coatings industry 1 federation of societies for coating technology, 4th edn. Blue Bell, Pennsylvania Vols I and IIGoogle Scholar
  17. Kukowska-Latallo JF, Candido KA, Cao Z, Nigavekar SS, Majoros IJ, Thomas TP, Balogh LP, Khan MK, Baker JR Jr (2005) Nanoparticle targeting of anticancer drug improves therapeutic response in animal model of human epithelial cancer. Cancer Res 65:5317–5324CrossRefGoogle Scholar
  18. Lee CC, MacKay JA, Fréchet JM, Szoka FC (2005) Designing dendrimers for biological applications. Nat Biotechnol 23:1517–1526CrossRefGoogle Scholar
  19. Lee CC, Gillies ER, Fox ME, Guillaudeu SJ, Fréchet JM, Dy EE, Szoka FC (2006) A single dose of doxorubicin-functionalized bow-tie dendrimer cures mice bearingC-26 colon carcinomas. Proc Natl Acad Sci USA 103:16649–16654CrossRefGoogle Scholar
  20. Liu WM, Xue YN, He WT, Zhuo RX, Huang SW (2011) Dendrimer modified magnetic iron oxide nanoparticle/DNA/PEI ternary complexes: a novel strategy for magnetofection. J Control Release 152:159–160CrossRefGoogle Scholar
  21. Mahmoudi M, Simchi A, Milani AS, Stroeve P (2009) Cell toxicity of superparamagnetic iron oxide nanoparticles. J Colloid Interface Sci 336(2):510–518CrossRefGoogle Scholar
  22. Majoros IJ, Keszler B, Woehler S, Bull T, Baker JR Jr (2003) Acetylation of poly(amidoamine) dendrimers. Macromolecules 36:5526–5529CrossRefGoogle Scholar
  23. Malik N, Evagorou EG, Duncan R (1999) Dendrimer-platinate: a novel approach to cancer chemotherapy. Anticancer Drugs 10:767–776CrossRefGoogle Scholar
  24. Malik N, Wiwattanapatapee R, Klopsch R, Lorenz K, Frey H, Weener JW, Meijer EW, Paulus W, Duncan R (2000) Dendrimers: relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo. J Control Release 65:133–148CrossRefGoogle Scholar
  25. Matsumura Y, Maeda H (1986) A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res 46:6387–6392Google Scholar
  26. Matsunaga T, Sato R, Kamiya S, Tanaka T, Takeyama H (1999) Chemiluminescence enzyme immunoassay using protein A-bacterial magnetite complex. J Magn Magn Mater 194:126–131CrossRefGoogle Scholar
  27. Menjoge AR, Kannan RM, Tomalia DA (2010) Dendrimer-based drug and imaging conjugates: design considerations for nanomedical applications. Drug Discov Today 15(5–6):171–185CrossRefGoogle Scholar
  28. Mornet S, Vekris A, Bonnet J, Duguet E, Grasset F, Choy JH, Portier J (2000) DNA–magnetite nanocomposite materials. Mater Lett 42:183–188CrossRefGoogle Scholar
  29. Pan BF, Gao F, Gu HC (2005) Dendrimer modified magnetite nanoparticles for protein immobilization. J Colloid Interface Sci 284(1):1–6CrossRefGoogle Scholar
  30. Pan B, Cui D, Sheng Y, Ozkan C, Gao F, He R, Li Q, Xu P, Huang T (2007) Dendrimer-modified magnetic nanoparticles enhance efficiency of gene delivery system. Cancer Res 67:8156–8163CrossRefGoogle Scholar
  31. Rahman O, Mohapatra SC, Ahmad S (2012) Fe3O4 inversespinal super paramagnetic nanoparticles. Mater Chem Phys 132:196–202CrossRefGoogle Scholar
  32. Reetz MT, Zonta A, Vijayakrishnan V, Schimossek K (1998) Entrapment of lipases in hydrophobic magnetite-containing sol–gel materials: magnetic separation of heterogeneous biocatalysts. J Mol Catal A 134:251–258CrossRefGoogle Scholar
  33. Sato N, Kobayashi H, Hiraga A, Saga T, Togashi K, Konishi J, Brechbiel MW (2001) Pharmacokinetics and enhancement patterns of macromolecular MR contrastagents with various sizes of polyamidoamine dendrimer cores. Magn Reson Med 46:1169–1173CrossRefGoogle Scholar
  34. Shimomura M, Abe T, Sato Y, Oshima K, Yamauchi T, Miyauchi S (2003) Sugar-binding property of magnetite particles modified with dihydroxyborylphenyl groups via graft polymerization of acrylic acid. Polymer 44:3877–3882CrossRefGoogle Scholar
  35. Shukla R, Thomas TP, Peters J, Kotlyar A, Myc A, Baker JR Jr (2005) Tumor angiogenic vasculature targeting with PAMAM dendrimer RGD conjugates. Chem Commun (Camb) 14:5739–5741CrossRefGoogle Scholar
  36. Shukoor MI, Natalio F, Ksenofontov V, Tahir MN, Eberhardt M, Theato P, Schröder HC, Müller WE, Tremel W (2007) Double-stranded RNA polyinosinic polycytidylic acid immobilized onto gamma-Fe2O3 nanoparticles by using a multifunctional polymeric linker. Small 3(8):1374–1378CrossRefGoogle Scholar
  37. Singh P, Gupta U, Asthana A, Jain NK (2008) Folate and folate-PEG PAMAM dendrimers: synthesis, characterization, and targeted anticancer drug delivery potential in tumor bearing mice. Bioconjug Chem 19(11):2239–2252CrossRefGoogle Scholar
  38. Slowing I, Trewyn BG, Lin VS (2006) Effect of surface functionalization of MCM-41-type mesoporous silica nanoparticles on the endocytosis by human cancer cells. J Am Chem Soc 128(46):14792–14793CrossRefGoogle Scholar
  39. Stiriba SE, Frey H, Haag R (2002) Dendritic polymers in biomedical applications: from potential to clinical use indiagnostics and therapy. Angew Chem Int Ed Engl 41:1329–1334CrossRefGoogle Scholar
  40. Svenson S (2009) Dendrimers as versatile platform in drug delivery applications. Eur J Pharm Biopharm 71:445–462CrossRefGoogle Scholar
  41. Svenson S, Tomalia DA (2005) Dendrimers in biomedical applications reflections on the field. Adv Drug Deliv Rev 57(15):2106–2129CrossRefGoogle Scholar
  42. Takeda K, Kaisho T, Akira S (2003) Toll-like receptors. Annu Rev Immunol 21:335–376CrossRefGoogle Scholar
  43. Tang Y, Li YB, Wang B, Lin RY, van Dongen M, Zurcher DM, Gu XY, Banaszak Holl MM, Liu G, Qi R (2012) Efficient in vitro siRNA delivery and intramuscular gene silencing using PEG-modified PAMAM dendrimers. Mol Pharm 9(6):1812–1821CrossRefGoogle Scholar
  44. Tanyolaç D, Özdural AR (2000) Preparation of low-cost magnetic nitrocellulose microbeads. React Funct Polym 45:235–242CrossRefGoogle Scholar
  45. Taylor JI, Hurst CD, Davies MJ, Sachsinger N, Bruce IJ (2000) Application of magnetite and silica–magnetite composites to the isolation of genomic DNA. J Chromatogr A 890:159–166CrossRefGoogle Scholar
  46. Thomas TP, Patri AK, Myc A, Myaing MT, Ye JY, Norris TB, Baker JR Jr (2004) Invitro targeting of synthesized antibody conjugated dendrimer nanoparticles. Biomacromolecules 5:2269–2274CrossRefGoogle Scholar
  47. Thomas TP, Majoros IJ, Kotlyar A, Kukowska-Latallo JF, Bielinska A, Myc A, Baker JR Jr (2005) Targeting and inhibition of cell growth by an engineered dendritic nanodevice. J Med Chem 48(11):3729–3735CrossRefGoogle Scholar
  48. Thorek DL, Tsourkas A (2008) Size, charge and concentration dependent uptake of iron oxide particles by non-phagocytic cells. Biomaterials 29(26):3583–3590CrossRefGoogle Scholar
  49. Tomalia DA, Baker H, Dewald J, Hall M, Kallos G, Martin S, Roeck J, Ryder J, Smith P (1985) A new class of polymers: starburst-dendritic macromolecules. Polym J 17:117–132CrossRefGoogle Scholar
  50. Unsoy G, Yalcın S, Khodadust R, Gunduz G, Gunduz U (2012) Synthesis optimization and characterization of chitosan-coated iron oxide nanoparticles produced for biomedical applications. J Nanopart Res 14:964CrossRefGoogle Scholar
  51. Uzun K, Çevik E, Şenel M, Sözeri H, Baykal A, Abasıyanık FM, Toprak SM (2010) Covalent immobilization of invertase on PAMAM-dendrimer modified superparamagnetic iron oxide nanoparticles. J Nanopart Res 12(8):3057–3067CrossRefGoogle Scholar
  52. Wuang SC, Neoh KG, Kang ET, Pack DW, DE Leckband (2007) Synthesis and functionalization of polypyrrole-Fe3O4 nanoparticles for applications in biomedicine. J Mater Chem 17:3354–3362CrossRefGoogle Scholar
  53. Zhuo RX, Du B, Lu ZR (1999) In vitro release of 5 fluorouracil with cyclic core dendritic polymer. J Control Release 57:249–257CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Department of BiotechnologyMiddle East Technical UniversityAnkaraTurkey
  2. 2.Department of Food EngineeringAhi Evran UniversityKırşehirTurkey
  3. 3.Department of Chemical EngineeringMiddle East Technical UniversityAnkaraTurkey
  4. 4.Department of Biological SciencesMiddle East Technical UniversityAnkaraTurkey

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