Advancing Kidney Nanowarming through Scaleable Coating of Iron Oxide Nanoparticles

点击翻译按钮获取中文摘要

Advancing Kidney Nanowarming through Scaleable Coating of Iron Oxide Nanoparticles ABSTRACT The inability to preserve donor kidneys for more than a few hours significantly contributes to organ shortages, poor organ matching, and poor quality of life for transplant recipients. Using radiofrequency excited iron oxide nanoparticles (IONPs) dispersed in cryoprotectants (CPAs), the Bischof group at the University of Minnesota has successfully rewarmed small (< 80 mL) cryopreserved (-140 ºC) biological samples, including a rabbit kidney. To reliably produce IONPs at a scale needed to nanowarm whole human kidneys, however, a simpler, biocompatible coated IONP is needed that 1) is stable in CPAs, 2) has a low volume fraction, and 3) is inexpensive and easy to produce in batches > 1g. To address this need, we designed an easy-to-make small-molecule phosphonate linker (PLink) which contains a phosphonate “anchor” for high irreversible binding to iron oxide and a carboxyl “handle” for ligand attachment. This linker enables ligands such as PEG to bind to IONPs without complex chemistry and can be used to coat > 1g of IONPs per batch. We already have preliminary data to show that this PLink coating method preserves heating and imaging IONP properties. In order to develop this technology for use in rewarming cryopreserved kidneys, we will 1) determine PLink coating effects on heating, imaging, and biocompatibility properties of two commercially available IONPs and one lab-made IONP, and 2) scale up coated IONP production for in vivo mouse studies and ex vivo rat kidney perfusion. When we have completed these aims, we will be able to produce stable coated IONPs in bulk, which will allow us to significantly accellerate the development of actual kidney cryopreservation and nanowarming for transplantation.