Evaluation of Tris cationic lipids as transport vehicles for platinum (II) complexes

Abstract

The objective of this project was to enhance the activity of existing and new platinum(II) complexes against cancer through encapsulation in cationic liposomes. In this study a range of platinum(II) complexes the type [Pt(intercalating ligand)(ancillary ligand)]2+ (where the intercalating ligands were: 1,10-phenanthroline, 5-methyl-1,10-phenanthroline, 5,6-dimethyl-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 3,4,7,8-tetramethyl-1,10-phenanthroline or 4- methyl-1,10-phenanthroline and the ancillary ligands were: 1S,2R- and 1R,2Rdiaminocyclohexane, 1,2-diaminoethane, 1,2R- and 1,2S-diaminopropane, 2S,3S-, 2R,3R- and 2S,3R-diaminobutane) were synthesised, characterised and biologically tested. The ligand 2,3-diaminobutane was synthesised and resolved. The resulting platinum compounds were characterised by one and two dimensional 1H, 13C and 195Pt NMR experiments. Complexes were also analysed by ESI-MS, microanalysis, UV-Vis and circular dichroism (CD) including synchrotron radiation circular dichroism (SRCD) spectroscopy. The platinum(II) complexes were tested against a range of cancerous cell lines to determine their cytotoxicity. Selected platinum(II) complexes were combined with K3C6TL3 liposomes and the resulting formulations were characterised by HPLC, DLS (dynamic light scattering), ESI-MS, synchrotron small angle X-ray scattering (SSAXS), 1H Pulsed Gradient Spin Echo (PGSE) NMR and linear dichroism (LD). The formulations were also used in preliminary cytotoxicity assays against a number of cancerous cell lines to determine if encapsulation enhances the activity of platinum(II) complexes.

Date of Award	2010
Original language	English