Anionic PAMAM dendrimers as drug delivery vehicles for transition metal-based anticancer drugs.
The use of anionic half-generation poly(amidoamine) dendrimers as drug delivery vehicles for [Pt(S,S-dach)(5,6-Me(2)phen)](2+) (56MESS) (where S,S-dach=1S,2S-diaminocyclohexane; 5,6-Me(2)phen=5,6-dimethyl-1,10-phenanthroline) and [{Delta,Delta-Ru(phen)(2)}(2)(mu-bb7)](4+) (Rubb(7)) (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 (1)H NMR spectra both 56MESS and Rubb(7) 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 Rubb(7) resulted in stronger binding to all dendrimer generations (K(b)> or =2 x 10(5)M(-1)) compared with 56MESS (K(b)> or =1 x 10(4)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.
Pisani
Michelle J
MJ
School of Physical, Environmental and Mathematical Sciences, University College, University of New South Wales, Northcott Drive, Campbell, ACT 2600, Australia.
Wheate
Nial J
NJ
Keene
F Richard
FR
Aldrich-Wright
Janice R
JR
Collins
J Grant
JG
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D001665:Binding Sites; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism*; D050091:Dendrimers; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000737:chemistry; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000737:chemistry; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000737:chemistry*; D011073:Polyamines / Q000008:administration & dosage / Q000737:chemistry*
C539772:(1,2-diaminocyclohexane)(5,6-dimethyl-1,10-phenanthroline)platinum(II); D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D050091:Dendrimers; D009942:Organometallic Compounds; D009944:Organoplatinum Compounds; C104700:PAMAM Starburst; D014677:Pharmaceutical Vehicles; D011073:Polyamines; C539773:bis(delta,delta-bis(1,10-phenanthroline)ruthenium(II))(mu-(1,7-bis(4-(4'-methyl-2,2'-bipyridyl)heptane)))