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首页> 外文期刊>RSC Advances >Organ preservation with targeted rapamycin nanoparticles: a pre-treatment strategy preventing chronic rejection in vivo
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Organ preservation with targeted rapamycin nanoparticles: a pre-treatment strategy preventing chronic rejection in vivo

机译：靶向雷帕霉素纳米颗粒的器官保存：一种预防体内慢性排斥反应的预处理策略

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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 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.
机译：低温保存是在器官移植之前保存器官的标准护理方法。与低温保存有关的内皮和上皮损伤导致下游移植物损伤，因此，理想的供体器官保存溶液的选择仍存在争议。通过设计，冷藏解决方案可最大程度地减少细胞坏死并优化细胞渗透潜能，但对缓解免疫细胞活化或移植后免疫细胞启动的作用很小。因此，在这里，我们探讨了我们先前描述的新型靶向雷帕霉素胶束（TRaM）作为威斯康星大学护理标准溶液保存添加剂的功效，以此作为使用气管和主动脉体内模型改变移植后免疫学微环境的手段同种异体移植。在所有移植模型中，与用游离雷帕霉素增强的UW相比，用10倍的游离雷帕霉素增强的UW移植，用100 ng mL〜（？1）TRaM增强的保存液离体预处理的移植物均显示出对移植后慢性排斥的显着抑制。更高的剂量。在这里，我们首次提出了一种使用基于纳米治疗的细胞靶向递送系统进行器官预处理的新方法，该系统能够在冷藏期间以10倍的剂量减少雷帕霉素的供体给药。在临床上，这些预处理策略可能会对移植后的结果产生积极影响，并且可以很容易地转化为临床方案。

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