Advancing Kidney Nanowarming through Scaleable Coating of Iron Oxide Nanoparticles

通过氧化铁纳米颗粒的可缩放涂层推进肾脏纳米变暖 摘要 无法将捐赠的肾脏保存超过几个小时，这在很大程度上导致了器官短缺， 器官匹配和移植受者的生活质量差。使用射频激发的氧化铁纳米颗粒 明尼苏达大学的Bischof小组成功地将IONP分散在冷冻保护剂（CPA）中， 复温的小块（< 80 mL）冷冻保存（-140 ºC）生物样本，包括一个兔肾。可靠地生产 然而，更简单的、生物相容性涂覆的IONP是 需要1）在CPA中稳定，2）具有低体积分数，和3）便宜且易于批量生产 > 1g。为了满足这一需求，我们设计了一种易于制备的小分子膦酸酯连接体（PLink）， 含有膦酸酯“锚”，用于与氧化铁高度不可逆结合，以及羧基“柄”，用于配体 附件.该接头使得配体如PEG能够在没有复杂化学的情况下与IONP结合，并且可以是可生物降解的。 用于每批涂覆> 1g的IONP。我们已经有初步数据表明，这种PLink涂层方法 保持加热和成像IONP属性。为了发展这项技术用于复温 我们将1）确定PLink涂层对加热、成像和生物相容性的影响 两种市售IONP和一种实验室制备的IONP的性质，以及2）按比例放大的涂覆的IONP 用于体内小鼠研究和离体大鼠肾灌注。当我们完成这些目标时，我们 将能够批量生产稳定的涂层IONP，这将使我们能够显着加速 发展真正的肾脏冷冻保存和移植。

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.