Abstract

Chemotherapy treatment and its secondary effects are devastating for patients and it is due to cellular resistance. So there is a scientific and medical interest in understanding cellular transport mechanisms of anti-cancer drugs. As part of this thesis, biomimetic models, in particular liposomes have been specially designed to study some of the transport mechanisms. While maintaining their simplicity, liposomes have been preferred over other models because their membranes are similar (structure and behaviour) to that of cell membranes. Thus, a bare liposome, a liposome with electroactive units encapsulated within its internal void and surface-modified redox liposornes were designed. In order to obtain the surface-modified redox liposome, the phospholipid headgroup of 1,2-distearoyl-sn -glycero-3-phosphocholine (DSPC) was first modified with an electroactive ferrocene derivative. The modification of the phospholipid headgroup with ferrocenemethanol led to the synthesis of an unstable redox phospholipid. Thus ferrocene-ethanol was preferred. Since the latter is a primary alcohol and DSPC is a choline bearing phospholipid, Phospholipase D-assisted transphosphatidylation was performed. To our knowledge, it is the first time an organometallic redox phospholipid was synthesised. The ferrocene group was attached covalently to the phospholipid headgroup and this was mostly verified by infrared studies. Mass spectrometry and 31phosphorus NMR spectroscopy were also used to quantify the reaction mixture. Cyclic voltammetry analysis confirmed that the functionalized phospholipid is indeed redox active. The ethylferrocene phospholipid was then used to produce surface-modified redox liposomes by the double emulsion technique. The liposome was immobilised by sedimentation by encapsulating sucrose within the liposome. Scanning electrochemical microscopy studies were performed on this redox active liposome, which mimicked a surface bound reaction. It was demonstrated, by chronoamperometry experiments, that its surface was not only electroactive, but its electrochemical response could be modulated upon the use of a specific sacrificial mediator. This preliminary investigation was only the beginning of a much larger SECM study on surface bound reactions at membranes. Finally, the design of a new ring microelectrode is presented. The fabrication steps of this microelectrode are simpler than what is already presented in the literature. Moreover, the use of pure platinum (and not an alloy) and the isolation of the micropipet by a silicon oxide coating make this distinct from others. However, cyclic voltammetry analysis combined with numerical simulations showed that during the ring exposure by focused ion beam the insulating properties of the silicon oxide layer are weakened. A small modification of this step would lead to the fabrication of a ring microelectrode suitable for SECM local probe