Advancing Kidney Nanowarming through Scaleable Coating of Iron Oxide Nanoparticles

利用氧化铁纳米粒子的可缩放涂层推进肾脏纳米武器 摘要 无法保存供体肾脏超过几个小时，极大地导致了器官短缺 器官匹配，移植受者的生活质量较差。使用射频激励的纳米氧化铁 (IONPs)分散在低温保护剂(CPA)中，明尼苏达大学的Bischof小组成功地 重新加热的小(&lt；80毫升)低温保存(-140℃)生物样本，包括兔肾。可靠地生产 然而，在纳米武器整个人类肾脏所需的规模上，更简单、生物兼容的包衣IONP是 需要1)在CPA中稳定，2)具有低体积分数，以及3)廉价且易于批量生产 &gt；1g。为了满足这一需求，我们设计了一种易于制造的小分子膦酸酯连接物(PLINK)，它 含有一个与氧化铁高度不可逆结合的磷酸盐“锚”和一个用于配基的羧基“柄”。 依恋。这种连接物使配体如聚乙二醇能够与IONPs结合，而不需要复杂的化学作用，并且可以 用于每批涂布1g IONPs。我们已经有初步数据表明，这种扣环涂层方法 保持加热和成像IONP属性。为了开发这项用于复温的技术 冷冻保存的肾脏，我们将1)确定粉红色涂层对加热、成像和生物相容性的影响 两个商用IONP和一个实验室制造的IONP的性质，以及2)放大涂层IONP 用于体内小鼠研究和体外大鼠肾脏灌流的生产。当我们完成这些目标时，我们 将能够批量生产稳定的包衣IONPs，这将使我们能够显著加速 用于移植的实际肾脏冷冻保存和纳米温控技术的发展。

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.