TY - JOUR
T1 - Anionic PAMAM dendrimers as drug delivery vehicles for transition metal-based anticancer drugs
AU - Pisani, Michelle J.
AU - Wheate, Nial J.
AU - Keene, F. Richard
AU - Aldrich-Wright, Janice R.
AU - Collins, J. Grant
PY - 2009/3
Y1 - 2009/3
N2 - 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.
AB - 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.
KW - Anionic dendrimer
KW - Drug delivery
KW - Nuclear magnetic resonance
KW - Platinum(II)
KW - Ruthenium(II)
UR - http://www.scopus.com/inward/record.url?scp=59649116847&partnerID=8YFLogxK
U2 - 10.1016/j.jinorgbio.2008.11.014
DO - 10.1016/j.jinorgbio.2008.11.014
M3 - Article
C2 - 19121543
AN - SCOPUS:59649116847
SN - 0162-0134
VL - 103
SP - 373
EP - 380
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
IS - 3
ER -