Flow cytometry studies of cell death and protection promoted by porphyrinoid compounds, phenothiazines and Teluranes associated to nanostructures in a cell biology multiuser lab

Abstract

The association of drugs and other compounds for the fundamental studies of nanostructures, cytotoxicity, cell death mechanisms, development of materials and advanced therapies have gained increasing interest in science. The relevance is evident in the high impact publications about this subject that is frequent in literature. Currently in our research group, the NanoBioMAv, we are conducting studies involving three classes of compounds with cytotoxic effects and protective antioxidant activity proven by studies in cells and isolated mitochondria. For some of these compounds the binding to nanostructures has proved to be able to modulate these effects and so, we intend to develop these supramolecular structures and for advances in the study of cellular effects.For porphyrinoid compounds we propose studies involving the incorporation andthe structural and functional characterization of hemin, microperoxidase, and cytochrome c-11 silica in mesoporous MCM-41and SBA-15. In addition, it will also be investigated if the affinity for cytochrome c and / or membrane lipids exhibited by the mesoporous silica contributes to the observed cytotoxicity of these nanostructures. In addition we also propose the association of hematite to mesoporous silicas to enable directional delivery. Regarding the phenothiazines, they are ongoing studies of the association of the phenothiazine nucleus (subject of a patent PI 0801368-3 funded by FAPESP -2006/03139-6) with PEG. This association leads to formation of nanoparticles currently in process of characterization. In addition, preliminary studies have shown that the antioxidant and photoprotective properties of phenothiazines are maintained and modulated by different PHT / PEG ratios and so we intend to start studies with melanocytes and other cells in culture to characterize their effects for future applications and cosmeceutic formulations.Regarding the teluranas we have obtained very interesting and relevant results about theiraction on mitochondrial bioenergetics and especially in the expression of antioxidant enzymes, particularly the thiol-rich proteins that are the focus of great interest today instudies involving cellular redox balance. Therefore, it is opportune to study the action and delivery of teluranas modulated by nanostructures as proposed in this project. Studies proposed for the three classes of compounds involve the use of flux cytometry, provided by the multi-user facility acquired by the project EMU-3 2009/54130-7 coordinated by the beneficiary of the present proposed project. Therefore by taking advantage of the demand of the above studies we intend to acquire aditional facilities (microscope, CO2 incubator and water purifier) that will allow us to construct a multiuser cell biology laboratory where the flux cytometer will be localized too (seeobservations and considerations). (AU)