Journal
RSC ADVANCES
Volume 8, Issue 46, Pages 25909-25919Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c8ra01555d
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Funding
- National Institutes of Health (NIH) National Institute of Biomedical Imaging and Biochemistry (NIBIB) [K08 EB019495]
- NIH Institutional Post-Doctoral Training Grant [HL007260]
- AHA [17CPOST33671205]
- NIH Institutional Pre-Doctoral Training Grants [4T32 HL007260, 5T32 GM008716]
- South Carolina Clinical & Translational Research (SCTR) Institute via NIH National Center for Advancing Translational Sciences (NCATS) grant [UL1 TR000062]
- National Natural Science Foundation of China [81700571]
- Barclay Patterson Memorial Foundation
- Small Animal Imaging Shared Resource, Hollings Cancer Center, Medical University of South Carolina [P30 CA138313]
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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 controversiall.(1,2) 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.
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