0_1543 Nanostructured natural compounds for the immunosurveillance manipulationAlessandra Invidia^1,2, Gabriele Maiorano², Giuseppe Gigli^1,2, Ilaria Elena Palamà²

1. Department of Mathematics and Physics, University of Salento, Monteroni Street, 73100 Lecce, Italy
2. Nanotechnology Institute, CNR-NANOTEC, Monteroni Street, 73100 Lecce, Italy

AbstractIn the last years, increasing attention is paid to the ability of several natural compounds such as polyphenols, terpenoids, alkaloids and cardiac glycosides, to manipulate the immune system against different diseases. In cancer these natural compounds can be result effective tools for immunogenic cell death (ICD) induction. However, one of the major obstacles to successful exploitations of these natural compounds is represented by their low bioavailability. For this reason, the employment of nanotechnology-based solutions represents a promising strategy to perform selective and controlled delivery of these compounds for the possibility to overcome biological barriers. In this context, polymeric nanoparticles (pNPs) can be appropriately designed in order to deliver precise doses of natural molecules, by simultaneously performing a desired targeting. Among natural compounds that potentially are ICD inducers, the cardiac glycoside digoxin was successfully encapsulated by solvent evaporation, by employing carboxyl-terminated polycaprolactone as building block. The resulting pNPs exhibited a size ranging from 100 to 300 nm, a suitable size for their accumulation in tumor tissues, Z-potential value of -29 mV and a good polydispersion index. Cytotoxicity analyses on glioblastoma cells show a low cell viability (<80%) for concentrations of digoxin ranging from 200 to 600 nM. According to these results, a concentration of 200 nM was adopted as the optimal one to evaluate pNPs uptake and their ability to deliver this compound and then, to induce a controlled cell death. Western Blot analyses revealed an intracellular overexpression of HMGB1 and HSP70/90 proteins in samples treated with nanostructured digoxin, these proteins are markers related to an active process of ICD. These results revealed promising in order to pursuit a proper nanostructuration of natural molecules such as digoxin, thus opening the way to the development of nanotechnological tools to achieve the manipulation of immunosurveillance in cold tumor, as glioblastoma.