Endothelial cells play a central role in the process of inflammation. Their biologic relevance, as well as their accessibility to IV injected therapeutics, make them a strong candidate for treatment with molecularly‐targeted nanomedicines. Typically, the properties of targeted nanomedicines are first optimized in vitro in cell culture and then in vivo in rodent models. While cultured cells are readily available for study, results obtained from isolated cells can lack relevance to more complex in vivo environments. On the other hand, the quantitative assays needed to determine the impact of nanoparticle design on targeting efficacy are difficult to perform in animal models. Moreover, results from animal models often translate poorly to human systems. To address the need for an improved testing platform, we developed an isolated vessel perfusion system to enable dynamic and quantitative study of vascular‐targeted nanomedicines in readily obtainable human vessels isolated from umbilical cords or placenta. We show that this platform technology enables the evaluation of parameters that are critical to targeting efficacy (including flow rate, selection of targeting molecule, and temperature). Furthermore, biologic replicates can be easily produced by evaluating multiple vessel segments from the same human donor in independent, modular chambers. The chambers can also be adapted to house vessels of a variety of sizes, allowing for the subsequent study of vessel segments in vivo following transplantation into immunodeficient mice. We believe this perfusion system can help to address long‐standing issues in endothelial targeted nanomedicines and thereby enable more effective clinical translation.

中文翻译：

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离体人体血管灌注系统，用于设计和评估针对内皮的纳米药物。


内皮细胞在炎症过程中发挥核心作用。它们的生物学相关性以及静脉注射疗法的可及性使它们成为分子靶向纳米药物治疗的有力候选者。通常，靶向纳米药物的特性首先在细胞培养物的体外进行优化，然后在啮齿动物模型的体内进行优化。虽然培养的细胞很容易用于研究，但从分离的细胞获得的结果可能与更复杂的体内环境缺乏相关性。另一方面，确定纳米颗粒设计对靶向功效的影响所需的定量测定很难在动物模型中进行。此外，动物模型的结果通常很难转化为人类系统。为了满足改进测试平台的需求，我们开发了一种离体血管灌注系统，以便能够在从脐带或胎盘分离的容易获得的人体血管中对血管靶向纳米药物进行动态和定量研究。我们表明，该平台技术能够评估对靶向功效至关重要的参数（包括流速、靶向分子的选择和温度）。此外，通过在独立的模块化室中评估来自同一人类供体的多个血管片段，可以轻松地产生生物复制品。这些腔室还可以适应容纳各种尺寸的血管，以便在移植到免疫缺陷小鼠体内后进行体内血管片段的后续研究。我们相信这种灌注系统可以帮助解决内皮靶向纳米药物中长期存在的问题，从而实现更有效的临床转化。