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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：具有靶向雷帕霉素纳米粒子的器官保存：预处理策略预防体内慢性排斥反应

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摘要

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.
机译：低温保存是在移植之前存放器官的护理标准。与低温储存相关的内皮和上皮损伤导致下游接枝损伤，因此，选择理想的供体器官保存溶液的选择仍然存在争议。（1,2）冷藏解决方案，通过设计，最大限度地减少细胞坏死和优化细胞渗透潜力，最大限度地减少蜂窝渗透潜力，但对缓和免疫细胞活化或免疫细胞启动后移植术。因此，在这里，我们探讨了我们以前描述的新型针对性雷帕霉素胶束（电车）作为威斯康星州水平保存解决方案的添加剂的疗效，作为改变在气管和主动脉的体内移植后移植的手段的手段同种异体移植移植。在所有型号的移植模型中，用100ng ml（-1）的电车增强保存溶液前体内预处理的移植物显示出对慢性排斥反射后移植后的显着抑制，与UW增强了以较高的自由雷帕霉素增强剂量。在此，我们首次介绍了使用纳米治疗性的细胞靶向递送系统的器官预处理的新方法，该递送系统能够在冷储存期间在10倍下减少的剂量下给予雷帕霉素。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，并且可以容易地翻译成临床情景。

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  • 来源
    《RSC Advances》 |2018年第46期|共11页
  • 作者

    Zhu Peng; Atkinson Carl; Dixit Suraj; Cheng Qi; Tran Danh; Patel Kunal; Jiang Yu-Lin; Esckilsen Scott; Miller Kayla; Bazzle Grace; Allen Patterson; Moore Alfred; Broome Ann-Marie; Nadig Satish N.;

  • 作者单位

    Med Univ South Carolina Dept Surg Div Transplant Surg Charleston SC 29425 USA;

    Med Univ South Carolina Dept Surg Div Transplant Surg Charleston SC 29425 USA;

    Med Univ South Carolina Dept Cell &

    Mol Pharmacol &

    Expt Therapeut Charleston SC 29425 USA;

    Med Univ South Carolina Dept Surg Div Transplant Surg Charleston SC 29425 USA;

    Med Univ South Carolina Dept Microbiol &

    Immunol Lee Patterson Allen Transplant Immunobiol Lab Charleston SC 29425 USA;

    Med Univ South Carolina Dept Surg Div Transplant Surg Charleston SC 29425 USA;

    Med Univ South Carolina Dept Cell &

    Mol Pharmacol &

    Expt Therapeut Charleston SC 29425 USA;

    Med Univ South Carolina Dept Surg Div Transplant Surg Charleston SC 29425 USA;

    Med Univ South Carolina Dept Cell &

    Mol Pharmacol &

    Expt Therapeut Charleston SC 29425 USA;

    Med Univ South Carolina Dept Microbiol &

    Immunol Lee Patterson Allen Transplant Immunobiol Lab Charleston SC 29425 USA;

    Med Univ South Carolina Dept Surg Div Transplant Surg Charleston SC 29425 USA;

    Med Univ South Carolina Dept Cell &

    Mol Pharmacol &

    Expt Therapeut Charleston SC 29425 USA;

    Med Univ South Carolina Dept Cell &

    Mol Pharmacol &

    Expt Therapeut Charleston SC 29425 USA;

    Med Univ South Carolina Dept Surg Div Transplant Surg Charleston SC 29425 USA;

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