Issue 46, 2018, Issue in Progress

Organ preservation with targeted rapamycin nanoparticles: a pre-treatment strategy preventing chronic rejection in vivo

Abstract

Hypothermic preservation is the standard of care for storing organs prior to transplantation. Endothelial and epithelial injury associated with hypothermic storage causes downstream graft injury and, as such, the choice of an ideal donor organ preservation solution remains controversial. Cold storage solutions, by design, minimize cellular necrosis and optimize cellular osmotic potential, but do little to assuage immunological cell activation or immune cell priming post transplantation. Thus, here we explore the efficacy of our previously described novel Targeted Rapamycin Micelles (TRaM) as an additive to standard-of-care University of Wisconsin preservation solution as a means to alter the immunological microenvironment post transplantation using in vivo models of tracheal and aortic allograft transplantation. In all models of transplantation, grafts pre-treated with 100 ng mL−1 of TRaM augmented preservation solution ex vivo showed a significant inhibition of chronic rejection post-transplantation, as compared to UW augmented with free rapamycin at a ten-fold higher dose. Here, for the first time, we present a novel method of organ pretreatment using a nanotherapeutic-based cellular targeted delivery system that enables donor administration of rapamycin, at a ten-fold decreased dose during cold storage. Clinically, these pretreatment strategies may positively impact post-transplant outcomes and can be readily translated to clinical scenarios.

Graphical abstract: Organ preservation with targeted rapamycin nanoparticles: a pre-treatment strategy preventing chronic rejection in vivo

Article information

Article type
Paper
Submitted
21 Feb 2018
Accepted
24 Jun 2018
First published
23 Jul 2018
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2018,8, 25909-25919

Organ preservation with targeted rapamycin nanoparticles: a pre-treatment strategy preventing chronic rejection in vivo

P. Zhu, C. Atkinson, S. Dixit, Q. Cheng, D. Tran, K. Patel, Y. Jiang, S. Esckilsen, K. Miller, G. Bazzle, P. Allen, A. Moore, A. Broome and Satish N. Nadig, RSC Adv., 2018, 8, 25909 DOI: 10.1039/C8RA01555D

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