DEVELOPMENT AND CHARACTERIZATION OF NANOCONJUGATED SYSTEMS FOR THERAPEUTIC TARGETING OF PATHOLOGICAL INFLAMMATORY MARKERS

Inflammation is a physiological response of the body to a damaging external or internal stimulus (such as infection by bacteria or viruses, lesion, tissue damage), and it implies several cellular events leading to the activation and migration of immune cells to the inflammatory focus, with the aim of defeating the causes of the pathological condition. However, it happens sometimes that the inflammatory response itself is responsible for the onset of a pathology; among the pathologies with an inflammatory involvement are atherosclerosis, some neurodegenerative diseases and cancer. Indeed, these diseases are characterized by the overexpression of some inflammatory markers, like adhesion molecules. Adhesion molecules are proteins involved in the interaction between circulating leukocytes and endothelial cells. The most expressed in our organism are selectins, integrins, VCAM-1 (Vascular Cell Adhesion Molecule 1) and ICAM-1 (InterCellular Adhesion Molecule 1). The aim of the project is to develop nanodispersed systems conjugated with directing devices capable of selective interaction with inflammatory markers, such as VCAM-1, ICAM-1 and selectins. Particularly, the objective is to prepare liposomes that could be used as targeted vehicles for drugs, which will be delivered in specific sites of the organism, for the treatment of pathologies like atherosclerosis, neurodegenerative diseases or cancer. The selected target is the protein VCAM-1, and our idea is to exploit a three-step pretargeting based on the biotin-avidin interaction. The first step involves NAMP, a previously synthesized biotin derivative linked to a VCAM-1 binding peptide. This molecule has been conceived to be administered parenterally, followed by injection of avidin or its derivatives streptavidin or neutravidin, to exploit the biotin-avidin high affinity complex (Kd 10-15 M); the pretargeting will be achieved by final administration of biotinylated liposomes.