Anionic PAMAM dendrimers as drug delivery vehicles for transition metal-based anticancer drugs

Michelle J. Pisani, N.J. Wheate, F. Richard Keene, J.R. Aldrich-Wright, J. Grant Collins

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The use of anionic half-generation poly(amidoamine) dendrimers as drug delivery vehicles for [Pt(S,S-dach)(5,6-Me2phen)]2+ (56MESS) (where S,S-dach = 1S,2S-diaminocyclohexane; 5,6-Me2phen = 5,6-dimethyl-1,10-phenanthroline) and [{Δ,Δ-Ru(phen)2}2(μ-bb7)]4+ (Rubb7) (where phen = 1,10-phenanthroline; bb7 = 1,7-bis[4-(4′-methyl-2,2′-bipyridyl)heptane]) has been studied by nuclear magnetic resonance spectroscopy. From one- and two-dimensional 1H NMR spectra both 56MESS and Rubb7 were found to bind to the surface of generation 3.5, 4.5, 5.5 and 6.5 dendrimers through electrostatic interactions. The higher charge and larger size of Rubb7 resulted in stronger binding to all dendrimer generations (Kb 2 × 105 M−1) compared with 56MESS (Kb 1 × 104 M−1). Interestingly, there appeared to be no observable trend between dendrimer size and binding constant strength. The size of the free and 56MESS-bound dendrimers were examined using pulsed-gradient spin-echo NMR. The dendrimers ranged in hydrodynamic diameter from 11 to 20 nm and in all cases were larger than their corresponding full-generation dendrimer. Upon the addition of 56MESS the diameter of the dendrimers increased, consistent with surface binding.
Original languageEnglish
Pages (from-to)373-380
Number of pages7
JournalJournal of Inorganic Biochemistry
Volume103
Issue number3
DOIs
Publication statusPublished - 2009

Keywords

  • drug delivery
  • anionic dendrimer
  • platinum(II)
  • ruthenium(II)
  • nuclear magnetic resonance

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