Mechanism of the membrane interaction of polynuclear platinum anticancer agents. Implications for cellular uptake.

摘要: The interaction between phospholipids and polynuclear platinum drugs was studied as a mechanism model for cellular uptake of anticancer drugs. by differential scanning calorimetry (DSC), 31P nuclear magnetic resonance spectroscopy (NMR), inductively coupled plasma optical emission (ICP-OES), electrospray ionization mass spectrometry (ESI-MS). transition temperature, enthalpy, entropy negatively charged DPPS, DPPA, DPPG were changed upon reaction with the trinuclear complex [{trans-PtCl(NH3)2}2μ-Pt(NH3)2{H2N(CH2)6NH2}2](NO3)4 (I, BBR3464) dinuclear analogue [{trans-PtCl(NH3)2}μ-{(NH2)(CH2)3NH2(CH2)4(NH2)}Cl3 (II, BBR3571). This suggests that these complexes interacted not only phosphate headgroup but also region fatty acid tail liposomes finally fluidity membrane. Both noncovalent (presumably electrostatic hydrogen bonding) covalent interactions were...