Membrane fluidity matters: Hyperthermia from the aspects of lipids and membranes

Hyperthermia is a promising treatment modality for cancer in combination both with radio- and chemotherapy. In spite of its great therapeutic potential, the underlying molecular mechanisms still remain to be clarified. Due to lipid imbalances and 'membrane defects' most of the tumour cells possess elevated membrane fluidity. However, further increasing membrane fluidity to sensitise to chemo-or radiotherapy could have some other effects. In fact, hyperfluidisation of cell membrane induced by membrane fluidiser initiates a stress response as the heat shock protein response, which may modulate positively or negatively apoptotic cell death. Overviewing some recent findings based on a technology allowing direct imaging of lipid rafts in live cells and lipidomics, novel aspects of the intimate relationship between the 'membrane stress' of tumour cells and the cellular heat shock response will be highlighted. Our findings lend support to both the importance of membrane remodelling and the release of lipid signals initiating stress protein response, which can operate in tandem to control the extent of the ultimate cellular thermosensitivity. Overall, we suggest that the fluidity variable of membranes should be used as an independent factor for predicting the efficacy of combinational cancer therapies

Photoinduced ultrafast dynamics of Ru(dcbpy)₂(NCS)₂-sensitized nanocrystalline TiO₂ films:The influence of sample preparation and experimental conditions

In most of the previous ultrafast electron injection studies of Ru(dcbpy)(2)(NCS)(2)-sensitized nanocrystalline TiO2 films, experimental conditions and sample preparation have been different from study to study and no studies of how the differences affect the observed dynamics have been reported. In the present paper, we have investigated the influence of such modifications. Pump photon density, environment of the sensitized film (solvent and air), and parameters of the film preparation (crystallinity and quality of the film) were varied in a systematic way and the obtained dynamics were compared to that of a well-defined reference sample: Ru(dcbpy)(2)(NCS)(2)-TiO2 in acetonitrile. In some cases, the induced changes in the dynamics were uncorrelated to the electron injection process. High pump photon density (not in the linear response region) and exposure of the sensitized film to air altered the picosecond-time- scale kinetics considerably, and the changes were attributed mostly to degradation of the dye. In other cases, changes in the measured kinetics were related to the electron injection processes: reducing the firing temperature of the nanocrystalline film or making the film via electron beam evaporation (EBE) resulted in a decrease of the overall crystallinity of the film, and the electron injection slowed. In the sensitized EBE films, in addition to an increased contribution of triplet excited-state electron injection, a new electron transfer (ET) process with a time constant of 200 fs was observed