Real-time visualization and quantitation of vascular permeability in vivo: implications for drug delivery.
Real-time visualization and quantitation of vascular permeability in vivo: implications for drug delivery.
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DOI：
10.1371/journal.pone.0033760
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Lewis JD
中科院分区：
文献类型：
--
作者：
Pink DB;Schulte W;Parseghian MH;Zijlstra A;Lewis JD
人类肿瘤的渗漏、异质性脉管系统阻碍了全身药物在癌组织内的均匀分布。然而，用于研究体内血管递送系统的技术通常需要复杂的哺乳动物模型和耗时的手术方案。发育中的鸡胚胎是一种成熟的人类癌症模型，很容易进行肿瘤成像。为了评估该模型用于肿瘤渗透性的体内分析，使人肿瘤在绒毛尿囊膜（CAM）上生长，所述绒毛尿囊膜是覆盖生长的鸡胚的薄血管膜。小的荧光葡聚糖通过肿瘤脉管系统和周围组织的实时移动被用于测量肿瘤异种移植物内的血管渗漏。白细胞介素-2（IL-2）肽片段或血管内皮生长因子（VEGF）选择性地增强肿瘤部位内的葡聚糖外渗。相对于周围正常组织，VEGF治疗增加了肿瘤中心的血管渗漏，并增加了人肿瘤异种移植物中的阿霉素摄取。这种新的系统很容易在体内可视化血管通透性的变化，并表明血管通透性可以被操纵，以提高化疗药物靶向肿瘤。
The leaky, heterogeneous vasculature of human tumors prevents the even distribution of systemic drugs within cancer tissues. However, techniques for studying vascular delivery systems in vivo often require complex mammalian models and time-consuming, surgical protocols. The developing chicken embryo is a well-established model for human cancer that is easily accessible for tumor imaging. To assess this model for the in vivo analysis of tumor permeability, human tumors were grown on the chorioallantoic membrane (CAM), a thin vascular membrane which overlays the growing chick embryo. The real-time movement of small fluorescent dextrans through the tumor vasculature and surrounding tissues were used to measure vascular leak within tumor xenografts. Dextran extravasation within tumor sites was selectively enhanced an interleukin-2 (IL-2) peptide fragment or vascular endothelial growth factor (VEGF). VEGF treatment increased vascular leak in the tumor core relative to surrounding normal tissue and increased doxorubicin uptake in human tumor xenografts. This new system easily visualizes vascular permeability changes in vivo and suggests that vascular permeability may be manipulated to improve chemotherapeutic targeting to tumors.
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