Targeted Drug Delivery in Transplantation: Use of Immunosuppressant Nanoparticle Therapy

A-M. Broome, S.K. Dixit, N. Levey, C. Atkinson, S.N. Nadig
Medical University of South Carolina, US

Keywords: tranplant, immunotherapy, rapamycin, T cells

Summary:

Immunosuppression carries a host of harmful side effects and globally suppresses the immune system. Therapies that exert local immunosuppression by targeting an allograft, while reducing systemic side effects could offer great potential. We explored the therapeutic potential of rapamycin encapsulated nanoparticles for focused delivery to a transplanted allograft. Using the hydrophobic property of rapamycin, we developed a self-assembly micelle nanoparticle. This Targeted Rapamycin Micelle (TRaM) was conjugated to a near-infrared fluorophore and platelet derived growth factor to facilitate tracking and cellular uptake in cells that overexpress PDGF receptor as a proof-of-concept. Size and fluorophore intensity was performed for quality control. TRaM nanoparticles measured 10-15 nm in size as determined by DLS. Imaging demonstrated cellular uptake of TRaM in cell lines overexpressing the target when compared to cells without or cells incubated with untargeted RaM. We demonstrate the successful incorporation of rapamycin into micelle nanoparticles which are taken up by cells via receptor-mediated endocytosis. These data set the stage for future experiments, where allograft-targeted TRaMs will be used to investigate focused immunosuppression. Clinically, this novel technology and focused delivery method could alleviate the side effect profile of systemic rapamycin and blunt the immune response at the level of the allograft.