Dendrimer 101

  • Lajos P. Balogh
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 620)


In this chapter dendrimer basics are reviewed. It is impossible to describe, refer to or even list the related literature (our “dendrimer” database consists of over 7,000 papers and patents), thus selection of references has been made based on personal preference, often choosing clarity over details and overarching principles instead of detailed chemical structures. A large number of excellent reviews are available to those who are interested in more detail in particular areas1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26. References will take the reader to original scientific papers that provide more detail about a particular topic, describe experiments, and draw conclusions reflecting each author’s personal views. Even listing of books and reviews must be partial, as they number in the hundreds.


Hyperbranched Polymer PAMAM Dendrimers Dendritic Polymer Dendrimer Molecule Propylene Imine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Dendrimer database at the Center for Molecular Design and Recognition web site ( Scholar
  2. 2.
    David K Smith, ed. Recent Developments in Dendrimer Chemistry: Tetrahedron. 2005; 59(22).Google Scholar
  3. 3.
    Tomalia DA, Frechet JMJ, eds. Dendrimers and Dendritic Polymers. Prog Polym Sci 2005; 30.Google Scholar
  4. 4.
    Aulenta F, Hayes W, Rannard S. Dendrimers: A new class of nanoscopic containers and delivery devices. Eur Polym J 2003; 39:1741–1771.CrossRefGoogle Scholar
  5. 5.
    Boas U, Peter M, Heegaard H. Dendrimers in drug research. Chem Soc Rev 2004; 33:43–63.PubMedCrossRefGoogle Scholar
  6. 6.
    Bosman AW, Janssen HM, Meijer EW. About dendrimers: Structure, physical properties, and applications. Chem Rev 1999; 99(7):1665–1688.PubMedCrossRefGoogle Scholar
  7. 7.
    Caminade AM, Laurent R, Majoral JP. Characterization of dendrimers. Adv Drug Deliv Reviews 2005; 57:2130–2146.CrossRefGoogle Scholar
  8. 8.
    Cloninger MJ. Biological applications of dendrimers. Curr Opin in Chem Biol 2002; 6:742–748.CrossRefGoogle Scholar
  9. 9.
    Crespo L, Sanclimens G, Pons M et al. Peptide and amide bond-containing dendrimers. Chem Rev 2005; 105:1663–1681.PubMedCrossRefGoogle Scholar
  10. 10.
    Niederhafner P, Sebestik J, Jezek J. Peptide dendrimers. J Peptide Sci 2005; 11:757–788.CrossRefGoogle Scholar
  11. 11.
    Florence T, ed. Dendrimers: A versatile targeting platform. Adv Drug Deliv Rev Vol 2005; 57(15).Google Scholar
  12. 12.
    Dvornic PR. PAMAMOS: The first commercial silicon-containing dendrimers and their applications. J Polym Sci Part A: Polym Chem 2006; 44(9):2755–2773.CrossRefGoogle Scholar
  13. 13.
    Dykes GM. Dendrimers: A review of their appeal and applications. J Chem Technol Biotechnol 2001; 76:903–918.CrossRefGoogle Scholar
  14. 14.
    Frechet JMJ, Tomalia DA, eds. Dendrimers and Other Dendritic Polymers. New York: John Wiley and Sons Ltd, 2002.Google Scholar
  15. 15.
    Grayson SM, Frechet JMJ. Convergent dendrons and dendrimers: From synthesis to applications. Chem Rev 2001; 101:3819–3867.PubMedCrossRefGoogle Scholar
  16. 16.
    Gorman C. Metallodendrimers: Structural diversity and functional behavior. Adv Mater 1998; 10(4):295–309.CrossRefGoogle Scholar
  17. 17.
    Majoral JP, Caminade AM. Dendrimers containing heteroatoms (Si, P, B, Ge, or Bi). Chem Rev 1999; 99:845–880.PubMedCrossRefGoogle Scholar
  18. 18.
    Maurice WPL, Baars A, Meijer EW. Dendrimers II — Architecture, nanostructure and supramolecular chemistry. Topics in Curr Chem 2000; 210:131–182.CrossRefGoogle Scholar
  19. 19.
    Newkome GR, Moorefield CN, Vögtle F. Dendrimers and dendrons: Concepts, syntheses, applications. Wiley VCH Weinheim 2001.Google Scholar
  20. 20.
    Newkome GR, Moorefield CN, Vögtle F. Dendritic macromolecules: Concepts, syntheses, perspectives. New York: Wiley-VCH, 1996.Google Scholar
  21. 21.
    Newkome GR, ed. Advances in Dendritic Macromolecules. Amsterdam, London, New York, Oxford, Shannon, Tokyo: JAI Press, Inc., (An Imprint of Elsevier Science), 2002:5.Google Scholar
  22. 22.
    Tomalia DA, Dvornic P. Dendritic polymers, divergent synthesis (Starburst polyamidoamine dendrimers). In: Salamone JC, ed. Polymeric Materials Encyclopedia, Vol. 3 (D-E). New York; CRC Press, 1996:1814–1830.Google Scholar
  23. 23.
    Tomalia DA, Frechet JMJ. Introduction to “Dendrimers and Dendritic Polymers”. Prog Polym Sci 2005; 30:217–219.CrossRefGoogle Scholar
  24. 24.
    Vögtle F, ed. Dendrimers: Top Curr Chem. Berlin: Springer and dendrimer related volumes thereof, 1998:197.Google Scholar
  25. 25.
    Vögtle F, Gestermann S, Hesse R et al. Functional dendrimers. Prog Polym Sci 2000; 25:987–1041.CrossRefGoogle Scholar
  26. 26.
    Zeng F, Zimmerman SC. Dendrimers in supramolecular chemistry: From molecular recognition to self-assembly. Chem Rev 1997; 97:1681–1712.PubMedCrossRefGoogle Scholar
  27. 27.
    Buhleier E, Wehner W, Vögtle F. “Cascade”-and “Nonskid-Chain-like” synthesis of molecular cavity topologies. Synthesis 1978, (3):155–158.Google Scholar
  28. 28.
    Tomalia DA, Baker H, Dewald J et al. A new class of polymers: Starburst®-dendritic macromolecules. J Polym J (Tokyo) 1985; 17:117–132.Google Scholar
  29. 29.
    Tomalia DA, Baker H, Dewald J et al. Dendritic macromolecules: Synthesis of starburst dendrimers. Macromol 1986; 19:2466–2468.CrossRefGoogle Scholar
  30. 30.
    de Brabander-van den Berg EMM, Meijer EW. Poly(propylene imine) dendrimers: Large-scale synthesis by hetereogeneously catalyzed hydrogenations. Angew Chem Int Ed 1993; 32:1308–1310.CrossRefGoogle Scholar
  31. 31.
    Majoral JP, Caminade AM. Divergent approaches to phosphorus-containing dendrimers and their functionalization. In: Vögtle F, ed. Dendrimers: Top Curr Chem. Berlin: Springer, 1998; 197:79–124.Google Scholar
  32. 32.
    Newkome GR. A Systematic nomenclature for cascade polymers. J Polym Sci Part A: Polym Chem 1993; 31(3):641–651.CrossRefGoogle Scholar
  33. 33.
    Tomalia DA, Dewald JR. Dense Star Polymers Having Core: Core Branches. Terminal Groups USP, 1983, (4,507,466).Google Scholar
  34. 34.
    Tomalia DA, Dewald JR, Hall MJ et al. First SPSJ Int Polym: Conference. Kyoto, Japan; 1984:65.Google Scholar
  35. 35.
    Tomalia DA, Naylor AM, Goddard IIIrd WA. Starburst dendrimers: Molecular-level control of size, shape, surface chemistry, topology, and flexibility from atoms to macroscopic matter. Angew Chem Int Ed Engl 1990; 29:138–175.CrossRefGoogle Scholar
  36. 36.
    Tomalia et al. US 4,558,120 A, 4,568,737A, US 4,587,329A, 4,631,337A etc.Google Scholar
  37. 37.
    Newkome GR, Yao Z, Baker GR et al. Cascade molecules: A new approach to micelles, A [27]-Arborol. J Org Chem 1985; 50:2003–2004.CrossRefGoogle Scholar
  38. 38.
    Launay N, Caminade AM, Lahana R et al. A general synthetic strategy for neutral phosphorus-containing dendrimers. Angew Chem Int Ed Eng 1994; 33:1589–1592.CrossRefGoogle Scholar
  39. 39.
    Schultz JL, Wilks ES. Dendritic and star polymers: Classification, nomenclature, structure representation, and registration in the DuPont SCION database. J Chem Inf Comput Sci 1998; 38:85–99.Google Scholar
  40. 40.
    Newkome GR, Young JK, Baker GR et al. Cascade polymers. pH dependence of hydrodynamic radii of acid terminated dendrimers. Macromol 1993; 26:2394–2396.CrossRefGoogle Scholar
  41. 41.
    Hummelen JC, van Dongen JLJ, Meijer EW. Electrospray mass spectrometry of poly(propylene imine) dendrimers — The issue of dendritic purity or polydispersity. Chem Eur J 1997; 3(9):1489–1493.CrossRefGoogle Scholar
  42. 42.
    Frey H. Degree of branching in hyperbranched polymers. 2. Enhancement of the DB: Scope and limitations. Acta Polymerica 1997; 48(8):298–309.CrossRefGoogle Scholar
  43. 43.
    Boogh L, Pettersson B, Månson JAE. Dendritic hyperbranched polymers as tougheners for epoxy resins. Polymer 1999; 40:2249.CrossRefGoogle Scholar
  44. 44.
    Duncan R, Izzo L. Dendrimer biocompatibility and toxicity. Adv Drug Deliv Rev 2005; 57:2215–2237.PubMedCrossRefGoogle Scholar
  45. 45.
    Wooley KL, Hawker CJ, Frechet JMJ. Hyperbranched macromolecules via a novel double-stage convergent growth approach. J Am Chem Soc 1991; 113:4252–4261.CrossRefGoogle Scholar
  46. 46.
    Wooley KL, Hawker CJ, Frechet JMJ. A “Branched-Monomer Approach” for the rapid synthesis of dendrimers. Angew Chem Int Ed 1994; 33:82–85.CrossRefGoogle Scholar
  47. 47.
    Kawaguchi T, Walker KL, Charles L et al. Double exponential dendrimer growth. J Am Chem Soc 1995; 117:2159–2165.CrossRefGoogle Scholar
  48. 48.
    deGennes PG, Hervet HJ. Statistics of starburst polymers. J Phys Lett (Paris) 1983; 44:L351–L360.Google Scholar
  49. 49.
    Peterson JV, Allikmaa JS, Pehk T et al. Structural deviations in poly(amidoamine) dendrimers: A MALDI-TOF MS analysis. Eur Polym J 2003; 39:33–42.CrossRefGoogle Scholar
  50. 50.
    Crooks RM, Buford I, Lemon IIIrd et al. Dendrimer-encapsulated metals and semiconductors: Synthesis. Characterization, and Applications Topics in Current Chemistry 2001; (212):81–135.Google Scholar
  51. 51.
    Tolic LP, Anderson GA, Smith RD et al. Electrospray ionization fourier transform ion cyclotron resonance mass spectrometric characterization of high molecular mass starburst dendrimers. Internat J Mass Spectr Ion Proc 1997; 165/166:405–418.CrossRefGoogle Scholar
  52. 52.
    Balogh LP, Shi X, Bányai I et al. Generational, skeletal and substitutional diversities in generation one poly(amidoamine) dendrimers. Polymer 2005; 46(9):3022–3034.CrossRefGoogle Scholar
  53. 53.
    Tomalia DA, Brothers IInd HM, Piehler LT et al. Partial shell-filled core-shell tecto(dendrimers) — A strategy to surface differentiated nano-clefts and cusps. PNAS 2002; 99(8):5081–5087.PubMedCrossRefGoogle Scholar
  54. 54.
    Mansfield ML. Dendron segregation in model dendrimers. Polymer 1994; 35:1827–1830.CrossRefGoogle Scholar
  55. 55.
    Ballauff M, Likos CN. Dendrimers in solution: Insight from theory and simulation. Angew Chem Int Ed Eng 2004; 43:2998–3020.CrossRefGoogle Scholar
  56. 56.
    Harreis HM, Likos CN, Ballauff M. Can dendrimers be viewed as compact colloids? A simulation study of the fluctuations in a dendrimer of fourth generation. J Chem Phys 2003; 118:1979–88.CrossRefGoogle Scholar
  57. 57.
    Balzani S, Campagna G, Denti A et al. Harvesting sunlight by artificial supramolecular antennae. Sol Energy Mater Sol cells 1995; 38:159–173.CrossRefGoogle Scholar
  58. 58.
    Stewart GM, Fox MA. Chromophore-labeled dendrons as light harvesting antennae. J Am Chem Soc 1996; 118:4354–4360.CrossRefGoogle Scholar
  59. 59.
    Kopelman R, Shortreed M, Shi ZY et al. Spectroscopic evidence for excitonic localization in fractal antenna supermolecules. Phys Rev Letters 1997; 78(7):1239–1242.CrossRefGoogle Scholar
  60. 60.
    Bar-Haim A, Klafter J. Dendrimers as light harvesting antennae. J Luminescence 1998; 76–77:197–200.CrossRefGoogle Scholar
  61. 61.
    Shortreed MR, Swallen SF, Shi ZY et al. Directed energy transfer funnels in dendrimeric antenna supermolecules. J Phys Chem B 1997; 101:6318–6322.CrossRefGoogle Scholar
  62. 62.
    Hawker CJ, Malmström EE, Frank CW et al. Exact linear analogs of dendritic polyether macromolecules: Design, synthesis, and unique properties. J Am Chem Soc 1997; 119:9903–9904.CrossRefGoogle Scholar
  63. 63.
    Tomalia DA. Birth of a new macromolecular architecture: Dendrimers as quantized building blocks for nanoscale synthetic polymer chemistry. Prog Polym Sci 2005; 30:294–324.CrossRefGoogle Scholar
  64. 64.
    Murat M, Grest GS. Molecular dynamics study of dendrimer molecules in solvents of varying quality. Macromolecules 1996; 29:1278–1285.CrossRefGoogle Scholar
  65. 65.
    Wooley KL, Hawker CJ, Frechet JMJ. Unsymmetrical three-dimensional macromolecules: Preparation and characterization of strongly dipolar dendritic macromolecules. J Am Chem Soc 1993; 115:11496–11505.CrossRefGoogle Scholar
  66. 66.
    Stechemesser S, Eimer W. Solvent-dependent swelling of poly(amidoamine) Starburst dendrimers. Macromol 1997; 30:2204–2206.CrossRefGoogle Scholar
  67. 67.
    Borkovec M, Koper GJM. Proton binding characteristics of branched polyelectrolytes. Macromol 1997; 30:2151–2158.CrossRefGoogle Scholar
  68. 68.
    van Duijvenbode RC, Rajanayagam A, Koper GJM et al. Synthesis and protonation behavior of carboxylate-functionalized poly(propyleneimine) dendrimers. Macromol 2000; 33:46–52.CrossRefGoogle Scholar
  69. 69.
    Cakara D, Kleimann J, Borkovec M. Microscopic protonation equilibria of poly(amidoamine) dendrimers from macroscopic titrations. Macromol 2003; 36:4201–4207.CrossRefGoogle Scholar
  70. 70.
    Jannerfeldt G, Boogh L, Månson JAE. Influence of hyperbranched polymers on the interfacial tension of polypropylene/polyamide-6 blends. J Polym Sci Part B: Polym Phys 1999; 37:2069–2077.CrossRefGoogle Scholar
  71. 71.
    Uppuluri S, Morrison FA, Dvornic PR. Rheology of dendrimers. 2. Bulk polyamidoamine dendrimers under steady shear, creep, and dynamic oscillatory shear. Macromolecules 2000; 33:2551–2560.CrossRefGoogle Scholar
  72. 72.
    Uppuluri S, Keinath SE, Tomalia DA et al. Rheology of dendrimers. I. Newtonian flow behavior of medium and highly concentrated solutions of polyamidoamine (pamam) dendrimers in ethylenediamine (eda) solvent. Macromolecules 1998; 31:4498–4510.CrossRefGoogle Scholar
  73. 73.
    Amiji M, ed. Nanotechnology in Cancer Therapy. Boca Raton, London, New York: CRC Press (Taylor and Francis Group), 2006.Google Scholar
  74. 74.
    Nigavekar SS, Balogh L, Khan MK. 3H dendrimer nanoparticle organ/tumor distribution. Pharm Res 2004; 21(3):476–83.PubMedCrossRefGoogle Scholar
  75. 75.
    Khan MK, Nigavekar SS, Balogh LP. In vivo biodistribution of dendrimers and dendrimer nanocomposites — Implications for cancer imaging and therapy. Technol Canc Res and Treatment 2005; 4(6):603–613.Google Scholar
  76. 76.
    Hong S, Bielinska AU, Mecke A et al. Interaction of poly(amidoamine) dendrimers with supported lipid bilayers and cells: Hole formation and the relation to transport. Bioconj Chem 2004; 15:774–782.CrossRefGoogle Scholar
  77. 77.
    Stiriba SE, Frey H, Haag R. Dendritic polymers in biomedical applications: From potential to clinical use in diagnostics and therapy. Angew Chem Int Ed 2002; 41(8):1329–1334.CrossRefGoogle Scholar
  78. 78.
    Balogh LP, Swanson DR, Spindler R et al. Formation and characterization of dendrimer-based water soluble inorganic nanocomposites. Proc ACS PMSE 1997;77:118–9.Google Scholar
  79. 79.
    Beck-Tan N, Balogh L, Trevino S. Structure of metallo-organic nanocomposites produced from dendrimer complexes. Proc ACS PMSE 1997; 77:120.Google Scholar
  80. 80.
    Balogh L, Tomalia DA. Poly(amidoamine) dendrimer-templated nanocomposites. 1. Synthesis of zerovalent copper nanoclusters. J Am Chem Soc 1998; 120:7355–7356.CrossRefGoogle Scholar
  81. 81.
    Gupta U, Agashe HB, Jain NK et al. Dendrimers: Novel polymeric nanoarchitectures for solubility enhancement. Biomacromol 2006; 7(3):649–658.CrossRefGoogle Scholar
  82. 82.
    Patri AK, Kukowska-Latallo JF, Baker Jr JR. Targeted drug delivery with dendrimers: Comparison of the release kinetics of covalently conjugated drug and noncovalent drug inclusion complex. Adv Drug Deliv Rev 2005; 57:2203–2214.PubMedCrossRefGoogle Scholar
  83. 83.
    Muggia FM. Doxorubicin-polymer conjugates: Further demonstration of the concept of enhanced permeability and retention. Clin Canc Res 1999; 5(1):7–8.Google Scholar
  84. 84.
    Bhadra D, Bhadra S, Jain S et al. A PEGylated dendritic nanoparticulate carrier of fluorouracil. Internat J of Pharmaceutics 2003; 257(1–2):111–124.CrossRefGoogle Scholar
  85. 85.
    Devarakonda B, Hill RA, Liebenberg W et al. Comparison of the aqueous solubilization of practically insoluble niclosamide by polyamidoamine (PAMAM) dendrimers and cyclodextrins. Internat J Pharmaceutics 2005; 304:193–209.CrossRefGoogle Scholar
  86. 86.
    Malik N, Evagorou EG, Duncan R. Dendrimer-platinate: A novel approach to cancer chemotherapy. Anti-cancer Drugs 1999; 10(8):767–775.PubMedCrossRefGoogle Scholar
  87. 87.
    Yiyun C, Tongwen X. Solubility of nicotinic acid in polyamidoamine dendrimer solutions. Eur J Med Chem 2005; 40:1384–1389.PubMedCrossRefGoogle Scholar
  88. 88.
    Yiyun C, Tongwen X, Rongqiang F. Polyamidoamine dendrimers used as solubility enhancers of ketoprofen. Eur J Med Chem 2005; 40:1390–1393.PubMedCrossRefGoogle Scholar
  89. 89.
    Quintana A, Raczka E, Piehler L et al. Design and function of a dendrimer-based therapeutic nanodevice targeted to tumor cells through the folate receptor. Pharm Res 2002; 19(9):1310–1316.PubMedCrossRefGoogle Scholar
  90. 90.
    Wiener EC, Konda S, Shadron A et al. Targeting dendrimer-chelates to tumors and tumor cells expressing the high-affinity folate receptor. Invest Radiol 1997; 32(12):748–54.PubMedCrossRefGoogle Scholar
  91. 91.
    Kukowska-Latallo JF, Candido KA, Cao Z et al. Nanoparticle targeting of anticancer drug improves therapeutic response in animal model of human epithelial cancer. Cancer Res 2005; 65(12):5317–5324.PubMedCrossRefGoogle Scholar
  92. 92.
    Patri AK, Myc A, Beals J et al. Synthesis and in vitro testing of J591 antibody-dendrimer conjugates for targeted prostate cancer therapy. Bioconj Chem 2004; 15:1174–1181.CrossRefGoogle Scholar
  93. 93.
    Shukla R, Thomas TP, Peters JL et al. HER2 specific tumor targeting with dendrimer conjugated anti-HER2 mAb, Bioconj Chem 2006;17(5):1109–1115.CrossRefGoogle Scholar
  94. 94.
    Kolhe P, Khandare J, Pillai O et al. Preparation, cellular transport, and activity of polyamidoamine-based dendritic nanodevices with a high drug payload. Biomaterials 2006; 27(4):660–669.PubMedCrossRefGoogle Scholar
  95. 95.
    Gurdag S, Khandare J, Sarah Stapels S et al. Activity of dendrimer-methotrexate conjugates on methotrexate-sensitive and-resistant cell lines. Bioconjugate Chem 2006; 17:275–283.CrossRefGoogle Scholar
  96. 96.
    Reuter JD, Myc A, Hayes MM et al. Inhibition of viral adhesion and infection by sialic-acid-conjugated dendritic polymers. Bioconj Chem 1999; 10:271–278.CrossRefGoogle Scholar
  97. 97.
    Majoros I, Myc A, Thomas T et al. PAMAM dendrimer-based multifunctional conjugate for cancer therapy: Synthesis, characterization, and functionality. Biomacromolecules 2006; 7:572–579.PubMedCrossRefGoogle Scholar
  98. 98.
    Zhao M, Sun L, Crooks RM. Preparation of Cu nanoclusters within dendrimer templates. J Am Chem Soc 1998;120:4877–4878.CrossRefGoogle Scholar
  99. 99.
    Esumi K, Suzuki A, Aihara N et al. Preparation of gold colloids with UV irradiation using dendrimers as stabilizer. Langmuir 1998; 14:3157–3159.CrossRefGoogle Scholar
  100. 100.
    Lesniak W, Bielinska AU, Balogh LP. Silver/Dendrimer nanocomposites as biomarkers: Fabrication, characterization, in vitro toxicity, and intracellular detection. Nano Letters 2005; 5(11):2123–2130.PubMedCrossRefGoogle Scholar
  101. 101.
    Balogh LP, Khan MK. Dendrimer nanocomposites for cancer therapy chapter 28. In: Mansour Amiji M, ed. Nanotechnology in Cancer Therapy. Boca Raton, London, New York: CRC Press (Taylor and Francis Group), 2006.Google Scholar
  102. 102.
    Maiti PK, Cagin T, Lin ST et al. Effect of solvent and pH on the structure of PAMAM dendrimers. Macromolecules 2005; 38:979–991.CrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2007

Authors and Affiliations

  • Lajos P. Balogh
    • 1
    • 2
  1. 1.Department of Radiation MedicineUniversity at Buffalo SUNYBuffaloUSA
  2. 2.Roswell Park Cancer Institute Department of OncologyUniversity at Buffalo SUNYBuffaloUSA

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