Nanoparticle-Based Interventions for Liver Transplantation

Abstract

Liver transplantation is the only treatment for hepatic insufficiency as a result of acute and chronic liver injuries/pathologies that fail to recover. Unfortunately, there remains an enormous and growing gap between organ supply and demand. Although recipients on the liver transplantation waitlist have significantly higher mortality, livers are often not allocated because they are (i) classified as extended criteria or marginal livers and (ii) subjected to longer cold preservation time (>6 h) with a direct correlation of poor outcomes with longer cold ischemia. Downregulating the recipient's innate immune response to successfully tolerate a graft having longer cold ischemia times or ischemia-reperfusion injury through induction of immune tolerance in the graft and the host would significantly improve organ utilization and post-transplant outcomes. Broadly, technologies proposed for development aim to extend the life of the transplanted liver through post-transplant or recipient conditioning. In this review, we focus on the potential benefits of nanotechnology to provide unique pre-transplant grafting and recipient conditioning of extended criteria donor livers using immune tolerance induction and hyperthermic pre-conditioning.

Keywords: hyperthermia; liver transplant; nanoparticles; tolerance.

Figure 1

Nanotechnology offers the potential to address donor liver shortages with new approaches to organ and donor preconditioning. Immune modulation of the liver with nanoparticles can expand the donor pool through conditioning. (A) Receptor blockade with nanoparticles offers the potential to reduce organ-rejecting immune responses by suppressing liver-specific pro-inflammatory immune receptors. (B) Donor endothelium conditioning can be achieved by blocking recognition by the recipient immune system of non-self MHC molecules present on endothelial cells in the vasculature of the donor graft using nanoparticle targeting. (C) Tolerance induction in recipients with nanoparticles potentially improves targeting efficiency with lower doses of nanoparticle-coated donor antigens and peptides to tolerize recipient immune cells or induce chimerism. (D) Hyperthermic perfusion with magnetic nanoparticle hyperthermia can be used to stimulate localized HSP upregulation and controlled organ-specific preconditioning. The yellow coil is a representation of the RF coil, which will be used to apply an alternating magnetic field (AMF).