FREE RADICALS IN BIO- AND NANO-TECHNOLOGY – Research

The involvement of free radicals in diverse fields, spanning from physics, materials, biology and medicine, indicates the flexibility and specificity of these important chemical intermediates. In bio- and nano-technology, free radical-based processes can be connected to innovative research dealing with the fate of drug nano-carriers as well as the efficacy of photo-induced processes, either for biological and biotechnological applications. The main objectives of the Laboratory are focused on (a) Models of DNA damage and consequences and (b) Free radical lipid transformations and lipidomics of radical stress.

  • Models of DNA damage and consequences

DNA transformations by free radical processes is an important area, for either health or biomarker development and for bio-nanotechnological applications. Tandem or clustered lesions and DNA/DNA or DNA/protein cross-links are correlated to various health conditions or drug treatments, being the repair machinery of the cell able to repair them. Moreover, processes as charge transfer in specific DNA sequences can be developed as applications to novel nanotechnologies. Our research is organized into the following areas: (i) Free-radical mechanistic studies of DNA oxidation based on biomimetic models and DNA damage/repair processes; (ii) Biomarker discovery and development of nucleic acid modifications, in view of providing a complete screening of DNA damages, for example for drug development. 5′,8-Cyclo-2’-deoxyadenosine (cdA) and 5′,8-cyclo-2′-deoxyguanosine (cdG) are tandem lesions produced by hydroxyl radicals of endogenous or exogenous origin that insult DNA by attacking the purine nucleosides (Figure 1). These lesions have been detected in γ-irradiated mammalian-cultured cells, human fluids and animal tissues as 5′R– and 5′S-diasteroisomers. Their presence is associated with pathological processes such as carcinogenesis, inflammation, and aging and with neurological disorders. Increased rates of reactive oxygen/nitrogen species (ROS/RNS) are involved in almost all cancer types, associated with tumor development and progression, causing damage to biomolecules such as nucleic acids.

Figure 1: Schematic hydroxyl radical attack to DNA with the formation of 5′,8-cyclo-2′-deoxyadenosine (cdA) and 5′,8-cyclo-2′-deoxyguanosine (cdG) lesions.

  • Free radical lipid transformations and lipidomics of radical stress

Free radical lipid transformations, envisages membranes as an important compartment for adaptation and metabolic recovery, through rapid reorganization and turnover. The following research aspects are developed: (i) Chemical basis and reactivity of free radicals with biological membranes; (ii) Lipid remodeling in vitro and in vivo under stress; (iii) Trans fatty acids and the role of biologically relevant small radicals in the cis-trans isomerization; (v) Endogenous protection of the cis-lipid geometry: the role of enzymatic and molecular defenses; (vi) Molecular libraries for recognition of trans lipids. The use of vesicles called liposomes, created by the aggregation of saturated and unsaturated phospholipids (Figure 2) represented advancement for chemical biology studies of these membrane biomimetic systems and for expanding drug delivery strategies. Over the years, liposomes have gained attention for carrying therapeutics, thanks to their high versatility combined with their high biological compatibility. Indeed, due to their amphiphilic properties, drugs with different partition coefficients can be incorporated into liposomes allowing control of the degradation rate and the harmful side effects. Moreover, the similarity of liposomes to biological membranes makes them non-immunogenic, physiologically inert and highly tolerated by the organism.

Figure 2: Molecular structures of l-α-phosphatidylcholine (A) and of fatty acid fragments (B); The comparison of oleic acid and elaidic acid structures to evidence the loss of the bent cis geometry (C); Reaction mechanism for the cistrans isomerization catalyzed by thiyl radicals (D).