Oxidative stress in many neurodegenerative diseases occurs when insufficient cellular antioxidant defense cannot control the levels of reactive oxygen species (ROS). Unsaturated fatty acids abundant in neuronal membranes are highly prone to lipid peroxidation. Therapeutically interesting compounds are flavonoids due to the multitude of their actions, such as anti-inflammatory, antibacterial, antioxidant etc., in all kinds of cells and tissues. For example, a high antioxidant activity of flavonoids in neurons has been recently demonstrated. The difficulty is the poor flavonoid solubility in water. Local increase in the flavonoid concentration could be realized by means of flavonoid encapsulation or adsorption into/onto nanocarriers in the form of nanoparticles (NPs). The present project is aimed to study the inhibition of lipid peroxidation of liposomes and supported lipid bilayers (SLBs) by free and encapsulated flavonoids from the subgroups of flavonols, anthocyanins and flavons.

We have envisaged a research of interactions of flavonoids with two and/or three component lipid membranes using the experimental techniques available in our laboratories: atomic force microscopy (AFM), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), and fluorescence microspectroscopy (FMS) upgraded with optical tweezers. Moreover, to further improve the spatial resolution of imaging a recently setup super-resolution STED fluorescence microscopy at the Jozef Stefan Institute will also be used. We want to investigate how the structural properties of flavonoids correlate with structural changes in liposomes and SLBs made of unsaturated phosphatidylcholine/sphingomyelin/cholesterol lipid mixtures. Such mixture resembles the lipid composition of humane brain white matter. The location and orientation of flavonoids affect membrane structure and function, notably their structural, thermotropical and elastic properties. These have not yet been quantified at the molecular level using such combination of powerful technique. Thus, such approach would much contribute to more complete understanding of the NP-lipid bilayer interactions.

We expect to find out how the biocompatible mesoporous NPs made of silica, magnetite and/or goethite loaded with flavonoids affect the organization and fluidity of the model membranes and whether the flavonoids embedded in NPs themselves permeate through and alter the membrane structure protecting their structure under oxidative stress conditions. Within this study we hope to gain more complete understanding of the mechanism of flavonoid action at the molecular level.