BIOINSPIRED NANODRUGS FOR CANCER THERAPY

Abstract

Cancer is a complex disease that can start mainly in any organ in the body when abnormal cells grow in an uncontrolled manner to invade neighbouring parts of the body to spread to other organs.The inhibition of proteins that control multiple oncogenic pathways could be a solution to treat cancer. One protein involved in multiple cellular pathways is peptidylprolyl PIN1 an isomerase formed by a WW domain and a catalytic domain with a molecular weight of 18 KDa. To identify molecules that are capable to inhibit in vivo PIN1, our laboratory collaborator used consensus docking to model existing PIN1‐ligand X‐ray structures and screened a chemical database for candidate inhibitors. This effective technique allowed identifying new hit compounds, thanks to receptor based on pharmacophore screening strategies which are commonly developed and applied on different classes of protein targets. Docking technique is used for in silico identification of novel hit compounds. Due to problem related to drug loading efficiency, in this study a compound C17 was obtained through docking, modified with pluronic acid and coated with albumin in order to increase the uptake of the drug. This formulation was used in order to increase the circulation half-life, since albumin can bind to the hydrophobic moieties of the C17 in order to prevent opsonization and phagocytosis. In the other side being albumin highly demanding source of energy of tumors, it has been used to improve the uptake of the drug by cancer cell lines.