The Role of Nanomedicine in Pancreatic Islet Transplantation

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by immunemediated destruction of insulin-producing beta-cells in the pancreas. It is the most common metabolic disease in the young, with incidence in childhood increasing steadily. T1DM is associated with dramatically increased mortality and morbidity, and is accompanied by enormous costs. All this clearly indicates that despite continuous improvements in the use of exogenous insulin, current T1DM therapeutic strategies are far from being fully satisfactory. An interesting alternative to insulin administration is represented by the transplantation of isolated islets, which has the advantage of restoring the lost beta-cell mass and re-establish the feedback between glycemic values and insulin release. However, the mandatory use of immunosuppressive agents, with their unavoidable adverse effects, remains one of the major limitations to a wider use of islet transplantation. This problem could be overcome if isolated islets are coated with materials able to protect the cells from immunological attacks while allowing normal cell nutrition and oxygenation. In addition, the use of appropriate anti-inflammatory molecules during islet transplantation and the possibility of tracking and homing the graft could represent major advances in the field. With all this in mind, in this doctoral project the candidate has explored the use of nanomedicine tools to evaluate the role of multilayer nanoencapsulation, anti-inflammatory nanostructures, and selective nanoparticle-guided homing in human islet transplantation for the treatment of T1DM. The main objectives pursued and reached during the course have been a) the development of a system to immunoprotect isolated human islets by a novel multi-layerby- layer nanocoating system, with maintenance of in-vitro viability and function; b) the evaluation of whether nanocoated human islets could cure chemically induced diabetes in mice; c) the assessment of the effects of anti-inflammatory nanomolecules on human islet properties; and d) the feasibility of tracking and transplanting human islets into laboratory animals using nanoparticle-guided homing. The overall results support the potential of the nanomedicine systems developed during this doctorate course for implementation in the human clinical setting.