Colloid and Polymer Science

, Volume 286, Issue 5, pp 563–569

Size-controlled synthesis of monodisperse core/shell nanogels

Original Contribution


Small, monodisperse nanogels (∼50-nm radius) were synthesized by free-radical precipitation polymerization and were characterized using a suite of light scattering and chromatography methods. Nanogels were synthesized with either N-isopropylacrylamide or N-isopropylmethacrylamide as the main monomer, with acrylic acid or 4-acrylamidofluorescein as a comonomer and N,N′-methylenebis(acrylamide) as a cross-linker. By varying the surfactant and initiator concentrations, particle size was controlled while maintaining excellent monodispersity. An amine-containing shell was added to these core particles to facilitate subsequent bioconjugation. Successful conjugation of folic acid to the particles was demonstrated as an example of how such materials might be employed in a targeted drug delivery system.


Nanogels Synthesis Bioconjugation Monodispersity Core/shell 





lower critical solution temperature




acrylic acid


enhanced permeability and retention


reticuloendothelial system


ammonium persulfate


sodium dodecyl sulfate




N-(3-aminopropyl) methacrylamide hydrochloride




dimethyl sulfoxide




multi-angle laser light scattering


asymmetric field flow fractionation


  1. 1.
    Heskins M, Guillet JE (1968) J Macromol Sci Chem A 2:1441–1455CrossRefGoogle Scholar
  2. 2.
    Tanaka T (1986) Physica A 140A:261–268CrossRefGoogle Scholar
  3. 3.
    Tanaka T, Fillmore DJ (1979) J Chem Phys 70:1214–1218CrossRefGoogle Scholar
  4. 4.
    Tanaka T, Fillmore DJ, Sun S-T, Nishio I, Swislow G, Shah A (1980) Phys Rev Lett 45:1636–1639CrossRefGoogle Scholar
  5. 5.
    Schild HG (1992) Prog Polym Sci 17:163–249CrossRefGoogle Scholar
  6. 6.
    Kim S, Healy KE (2003) Biomacromolecules 4:1214–1223CrossRefGoogle Scholar
  7. 7.
    Pelton RH, Chibante P (1986) Colloids Surf 20:247–256CrossRefGoogle Scholar
  8. 8.
    Lutolf MP, Raeber GP, Zisch AH, Tirelli N, Hubbell JA (2003) Adv Mater 15:888–892CrossRefGoogle Scholar
  9. 9.
    Langer R (1998) Nature 392:5–10Google Scholar
  10. 10.
    Langer R (2000) Acc Chem Res 33:94–101CrossRefGoogle Scholar
  11. 11.
    Langer R (2001) Science 293:58–59CrossRefGoogle Scholar
  12. 12.
    Nayak S, Lee H, Chmielewski J, Lyon LA (2004) J Am Chem Soc 126:10258–10259CrossRefGoogle Scholar
  13. 13.
    Nayak S, Lyon LA (2005) Angew Chem Int Ed 44:7686–7708CrossRefGoogle Scholar
  14. 14.
    Kim J, Nayak S, Lyon LA (2005) J Am Chem Soc 127:9588–9592CrossRefGoogle Scholar
  15. 15.
    Kim J, Serpe MJ, Lyon LA (2004) J Am Chem Soc 126:9512–9513CrossRefGoogle Scholar
  16. 16.
    Holtz JH, Asher SA (1997) Nature 389:829–832CrossRefGoogle Scholar
  17. 17.
    Plunkett KN, Berkowski KL, Moore JS (2005) Biomacromolecules 6:632–637CrossRefGoogle Scholar
  18. 18.
    Pelton R (2000) Adv Coll Inter Sci 85:1–33CrossRefGoogle Scholar
  19. 19.
    Saunders BR, Vincent B (1999) Adv Coll Inter Sci 80:1–25CrossRefGoogle Scholar
  20. 20.
    Snowden MJ, Vincent B (1992) J Chem Soc Chem Commun 1103–1105 (DOI 10.1039/C39920001103)
  21. 21.
    Zhou G, Elaissari A, Delair T, Pichot C (1998) Coll Polym Sci 276:1131–1139CrossRefGoogle Scholar
  22. 22.
    Gan D, Lyon LA (2001) J Am Chem Soc 123:7511–7517CrossRefGoogle Scholar
  23. 23.
    Jones CD, Lyon LA (2000) Macromolecules 33:8301–8306CrossRefGoogle Scholar
  24. 24.
    Jones CD, Lyon LA (2003) Macromolecules 36:1988–1993CrossRefGoogle Scholar
  25. 25.
    Berndt I, Pedersen JS, Lindner P, Richtering W (2006) Prog Colloid Polym Sci 133:35–40CrossRefGoogle Scholar
  26. 26.
    Berndt I, Popescu C, Wortmann F-J, Richtering W (2006) Angew Chem Int Ed 45:1081–1085CrossRefGoogle Scholar
  27. 27.
    Berndt I, Richtering W (2003) Macromolecules 36:8780–8785CrossRefGoogle Scholar
  28. 28.
    Duracher D, Elaissari A, Pichot C (1999) Coll Polym Sci 277:905–913CrossRefGoogle Scholar
  29. 29.
    Duracher D, Elaissari A, Pichot C (1999) J Polym Sci A Polym Chem 37:1823–1837CrossRefGoogle Scholar
  30. 30.
    Drummond DC, Meyer O, Hong K, Kirpotin DB, Papahadjopoulos D (1999) Pharmacol Rev 51:691–743Google Scholar
  31. 31.
    Hobbs SK, Monsky WL, Yuan F, Roberts WG, Griffith L, Torchilin VP, Jain RK (1998) Proc Natl Acad Sci 95:4607–4612CrossRefGoogle Scholar
  32. 32.
    Yuan F, Dellian M, Fukumura D, Leunig M, Berk DA, Torchilin VP, Jain RK (1995) Cancer Res 55:3752–3756Google Scholar
  33. 33.
    Matsumura Y, Maeda H (1986) Cancer Res 46:6387–6392Google Scholar
  34. 34.
    Maeda H (2001) Adv Enzyme Regul 41:189–207CrossRefGoogle Scholar
  35. 35.
    Maeda H, Seymour LW, Miyamoto Y (1992) Bioconjugate Chem 3:351–362CrossRefGoogle Scholar
  36. 36.
    Brannon-Peppas L, Blanchette JO (2004) Adv Drug Del Rev 56:1649–1659CrossRefGoogle Scholar
  37. 37.
    Storm G, Belliot SO, Daemen T, Lasic DD (1995) Adv Drug Del Rev 17:31–48CrossRefGoogle Scholar
  38. 38.
    Odian G (2004) Principles of polymerization, 4th edn. Wiley, New YorkGoogle Scholar
  39. 39.
    Serpe MJ, Jones CD, Lyon LA (2003) Langmuir 19:8759–8764CrossRefGoogle Scholar
  40. 40.
    Dube D, Francis M, Leroux J-C, Winnik FM (2002) Bioconjugate Chem 13:685–692CrossRefGoogle Scholar
  41. 41.
    Leamon CP, Cooper SR, Hardee GE (2003) Bioconjugate Chem 14:738–747CrossRefGoogle Scholar
  42. 42.
    Leamon CP, Low PS (1991) Proc Natl Acad Sci 88:5572–5576CrossRefGoogle Scholar
  43. 43.
    Leamon CP, Low PS (2001) Drug Discov Today 6:44–51CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.School of Chemistry and Biochemistry & Petit Institute for Bioengineering and BioscienceGeorgia Institute of TechnologyAtlantaUSA

Personalised recommendations