An electroanalytical toolbox for bioapplications

Abstract

This thesis describes the utilization of electrochemical methods for studying polyion-surfactant interactions, drug transfer through biomimetic phospholipid membranes and lateral charge transfer in DNA. Different aspects of oligonucleotide drug development and the corresponding delivery problem are considered and thus, the literature review in the beginning of the thesis is divided into four parts, giving an overview of the research field. The problem of oligonucleotide delivery has been approached using a surface-active compound as a carrier for the oligonucleotide. The complexation of the oligonucleotide with the surfactant shields most of the oligonucleotide's negative charges, thus making its incorporation into the lipophilic cell membrane and transfer through it more probable. Thermodynamics and kinetics of surfactant-oligonucleotide binding have been measured using advanced electrochemical methods based on the electrified liquid-liquid interface. A micropipette-based technique provided information on the stability and energetics of surfactant-oligonucleotide complexes, as well as the degree of binding. The kinetics of the surfactant-oligonucleotide interaction has been approached with a hydrodynamic technique enabling the control of the residence time of surfactant and oligonucleotide. Membrane activity is the most important property of the oligonucleotide-carrier complex. Carrier complexes should penetrate the biological phospholipid membrane, then escape the interior of the lipid membrane and transfer to the interior of the cell. Membrane activity of the surfactant-oligonucleotide complexes has been studied using a biomimetic phospholipid monolayer immobilised at an electrified liquid-liquid interface. In a related study, charge transfer in DNA immobilized on silicon surface has been studied by scanning electrochemical microscopy (SECM) to get fundamental information on nano-sized immobilized DNA-architectures.