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Immunosuppressive nano-therapeutic micelles downregulate endothelial cell inflammation and immunogenicity

机译：免疫抑制纳米治疗胶束下调内皮细胞炎症和免疫原性

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摘要

In this study, we developed a stable, nontoxic novel micelle nanoparticle to attenuate responses of endothelial cell (EC) inflammation when subjected to oxidative stress, such as observed in organ transplantation. Targeted Rapamycin Micelles (TRaM) were synthesized using PEG-PE-amine and N-palmitoyl homocysteine (PHC) with further tailoring of the micelle using targeting peptides (cRGD) and labeling with far-red fluorescent dye for tracking during cellular uptake studies. Our results revealed that the TRaM was approximately 10 nm in diameter and underwent successful internalization in Human Umbilical Vein EC (HUVEC) lines. The uptake efficiency of TRaM nanoparticles was improved with the addition of a targeting moiety. In addition, our TRaM therapy was able to downregulate both mouse cardiac EC (MCEC) and HUVEC production and release of the pro-inflammatory cytokines IL-6 and IL-8 in normal oxygen tension and hypoxic conditions. We were also able to demonstrate a dose-dependent uptake of TRaM therapy into biological tissues ex vivo. Taken together, these data demonstrate the feasibility of targeted drug delivery in transplantation, which has the potential for conferring local immunosuppressive effects without systemic consequences while also dampening endothelial cell injury responses.
机译：在这项研究中，我们开发了一种稳定的无毒新型胶束纳米粒子，以在经受氧化应激时衰减内皮细胞（EC）炎症的响应，例如在器官移植中观察到。使用PEG-PE-胺和N-棕榈酰同型半胱氨酸（PHC）合成靶向雷帕霉素胶束（电车），使用靶向肽（CRGD）进一步剪裁，并用远红荧光染料标记用于在细胞摄取研究期间跟踪。我们的研究结果表明，电车直径约为10纳米，人脐静脉EC（HUVEC）线上的成功内化。通过添加靶向部分改善了电车纳米颗粒的吸收效率。此外，我们的电车疗法能够在正常氧气张力和缺氧条件下使小鼠心脏EC（MCEC）和HUVEC生产和释放促炎细胞因子IL-6和IL-8释放。我们还能够证明将电车疗法的剂量依赖于生物组织exvivo。这些数据一起展示了移植中靶向药物递送的可行性，这具有赋予局部免疫抑制作用的可能性而不会在没有系统后果的同时抑制内皮细胞损伤反应。

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  • 来源
    《RSC Advances》 |2015年第54期|共11页
  • 作者

    Nadig Satish N.; Dixit Suraj K.; Levey Natalie; Esckilsen Scott; Miller Kayla; Dennis William; Atkinson Carl; Broome Ann-Marie;

  • 作者单位

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

    Med Univ S Carolina Dept Radiol &

    Radiol Sci Charleston SC 29425 USA;

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

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

    Med Univ S Carolina Dept Radiol &

    Radiol Sci Charleston SC 29425 USA;

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

    Med Univ S Carolina Dept Microbiol &

    Immunol Charleston SC 29425 USA;

    Med Univ S Carolina Dept Radiol &

    Radiol Sci Charleston SC 29425 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
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