Three-dimensional (3D) visualization of tumor vasculature is a key factor in accurate evaluation of RNA interference (RNAi)-based antiangiogenic nanomedicine, a promising approach for cancer therapeutics. However, this remains challenging because there is not a physiologically relevant in vitro model or precise analytic methodology. To address this limitation, a strategy based on 3D microfluidic angiogenesis-on-a-chip and 3D tumor vascular mapping was developed for evaluating RNAi-based antiangiogenic nanomedicine. We developed a microfluidic model to recapitulate functional 3D angiogenic sprouting when co-cultured with various cancer cell types. This model enabled efficient and rapid assessment of antiangiogenic nanomedicine in treatment of hyper-angiogenic cancer. In addition, tissue-clearing-based whole vascular mapping of tumor xenograft allowed extraction of complex 3D morphological information in diverse quantitative parameters. Using this 3D imaging-based analysis, we observed tumor sub-regional differences in the antiangiogenic effect. Our systematic strategy can help in narrowing down the promising targets of antiangiogenic nanomedicine and then enables deep analysis of complex morphological changes in tumor vasculature, providing a powerful platform for the development of safe and effective nanomedicine for cancer therapeutics.

中文翻译：

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3D微流控平台和肿瘤血管定位，用于评估基于抗血管生成RNAi的纳米药物。

肿瘤脉管系统的三维（3D）可视化是准确评估基于RNA干扰（RNAi）的抗血管生成纳米药物的关键因素，这是一种有前途的癌症治疗方法。但是，这仍然具有挑战性，因为没有生理相关的体外模型或精确的分析方法。为了解决这一局限性，开发了一种基于3D微芯片血管生成和3D肿瘤血管映射的策略，用于评估基于RNAi的抗血管生成纳米药物。我们开发了一种微流体模型，与各种癌细胞类型共培养时，可概括功能性3D血管新生。该模型能够高效，快速地评估抗血管生成纳米药物治疗高血管生成癌的能力。此外，基于组织清除的肿瘤异种移植物的全血管图谱可以提取各种定量参数中的复杂3D形态学信息。使用基于3D成像的分析，我们观察到了抗血管生成作用的肿瘤亚区域差异。我们的系统策略可以帮助缩小抗血管生成纳米药物的前景，然后能够深入分析肿瘤脉管系统中复杂的形态学变化，为开发安全有效的用于癌症治疗的纳米药物提供强大的平台。