Spectroscopic Investigation of Interactions of New Potential Anticancer Drugs with DNA and Non-Ionic Micelles

摘要

Photophysical properties of some azinium iodides in aqueous solution of nanostructured systems as DNA and nonionic micelles were investigated using steady-state and ultrafast time-resolved spectroscopy. Spectrophotometric and fluorimetric titrations of the investigated compounds with salmon testes DNA supplied evidence of a good interaction between the salts and DNA with binding constants of 10(4)-10(6)M(-1), making them interesting for pharmaceutical applications. The interaction with DNA also changes the photobehavior of the compounds, increasing the radiative deactivation pathway to the detriment of internal conversion and slowing down the excited state dynamics. The interaction of the azinium salts with the nonionic surfactant Triton X-100 from premicellar to postmicellar concentration was studied by spectrophotometric and fluorimetric titrations evidencing the ability of the micelles to associate the studied salts in their hydrophobic portion and to release them in the presence of DNA, acting as promising drug carriers. Also transient absorption spectroscopy with femtosecond resolution demonstrated the insertion of the investigated compounds into micellar aggregates. Preliminary measurements by confocal fluorescence microscopy on MCF-7 cells in the presence of the studied azinium salts showed that they are able to cross the cellular membrane and that their cytotoxicity can be expressed through interaction with DNA (RNA). In fact, they showed a significant fluorescence signal in all cell compartments, particularly (for 2 and 3) into punctuate structures within the nuclei compatible with a localization into the nucleoli.