Polymeric nanocarriers must overcome several biological barriers to reach the vicinity of solid tumors and deliver their encapsulated drug. This study assessed the in vitro and in vivo passage through the blood vessel wall to tumors of two well-characterized polymeric nanocarriers: poly(ethyleneglycol-b-ε-caprolactone) micelles and polymersomes charged with a fluorescent membrane dye (DiO: 3,3'-dioctadecyloxacarbo-cyanine perchlorate). The internalization and translocation from endothelial (human primary endothelial cells HUVEC) to cancer cells (human tumor cell line HCT-116) was studied in conventional 2D monolayers, 3D tumor spheroids, or in an endothelium model based on transwell assay. Micelles induced a faster DiO internalization compared to polymersomes but the latter crossed the endothelial monolayer more easily. Both translocation rates were enhanced by the addition of a pro-inflammatory factor or in the presence of tumor cells. These results were confirmed by early in vivo experiments. Overall, this study pointed out the room for the improvement of polymeric nanocarriers design to avoid drug losses when crossing the blood vessel walls.

中文翻译：

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从内皮到肿瘤组织的旅程：PEO-PCL 胶束和聚合物囊泡纳米载体之间的独特行为。

聚合物纳米载体必须克服多种生物屏障才能到达实体瘤附近并递送其封装的药物。本研究评估了两种特征良好的聚合物纳米载体在体外和体内通过血管壁到达肿瘤的能力：聚（乙二醇-b-ε-己内酯）胶束和带有荧光膜染料（DiO：3,3）的聚合物囊泡'-二十八烷基氧羰花青高氯酸盐）。在传统的 2D 单层、3D 肿瘤球体或基于 Transwell 测定的内皮模型中研究了从内皮（人原代内皮细胞 HUVEC）到癌细胞（人肿瘤细胞系 HCT-116）的内化和易位。与聚合物囊泡相比，胶束诱导了更快的 DiO 内化，但后者更容易穿过内皮单层。通过添加促炎因子或在存在肿瘤细胞的情况下，两种易位率均得到增强。这些结果得到了早期体内实验的证实。总的来说，这项研究指出了聚合物纳米载体设计的改进空间，以避免药物穿过血管壁时的损失。