Efficacy of imatinib loaded-antiCD44 coated gold nanoparticles: a possible new therapeutic approach to BOS

Gold nanoparticles (GNPs) can be exploited for local and targeted treatment for poorly prognosis diseases. Bronchiolitis Obliterans Syndrome (BOS) is the main cause of medium-term failure of lung transplantation and characterized by fibroobliteration of small airways due to uncontrolled proliferation of mesenchymal cells (MCs). Since CD44 receptor is overexpressed by BOS MCs, we developed GNPs decorated with the half chain of moAb against CD44 (GNP-HC). We aimed firslty to assess the in vitro activity of GNP-HC loaded with imatinib (GNP-HCim), a cAbl inhibitor already used in the treatment of chronic pulmonary GVHD. Furthermore we aimed to evaluate efficacy of local delivery of these carrier in heterotopic tracheal transplantation model in mice. For in vitro experiments, we evaluated cytotoxicity of GNP-HC, GNP-HCim and imatinib alone in BOS-derived MCs. Moreover, we performed in vivo experiments in mouse heterotopic trachea transplantation, with continuous intratracheal administration of GNP or vehicle by Alzet Model 2004 miniosmotic pumps, in order to assess their efficacy. GNP-HCim treated MCs showed significantly reduced viability than GNP-HC and imatinib alone, associated to induction of apoptosis (50 ± 0.5 % for GNP-HCim vs. GNP-HC 40 ± 0.35 % and Imatinib alone 30 ± 1.2 %). These results were strengthened by animal model, in which the percentage of tracheal obliterated area was significantly reduced by GNP-HCim (12.99 ± 2.5%) respect to GNP-HC (46.79± 5.7%) and vehicle treated tracheas (30.92 ± 5.8%). GNPs represent a valid vehicle for local and selective drug administration avoiding systemic toxicity.