Vascular permeability in a human tumor xenograft: molecular size dependence and cutoff size.
Vascular permeability in a human tumor xenograft: molecular size dependence and cutoff size.
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DOI：
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发表时间：
1995-09
期刊：
影响因子：
11.2
通讯作者：
Fan Yuan;M. Dellian;D. Fukumura;M. Leunig;D. Berk;V. Torchilin;R. Jain
中科院分区：
文献类型：
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作者：
Fan Yuan;M. Dellian;D. Fukumura;M. Leunig;D. Berk;V. Torchilin;R. Jain
分子大小是肿瘤中治疗药物跨血管转运的关键决定因素之一。然而，文献中没有关于肿瘤微血管通透性的分子大小依赖性的数据。因此，我们测量了移植到严重联合免疫缺陷小鼠背侧皮肤室的人结肠腺癌LS174T中各种大分子的微血管通透性。这些分子被荧光标记并静脉注射。变成老鼠。根据活体荧光显微镜技术测量的荧光强度计算微血管通透性。渗透率值在25,000至160,000的分子量范围内变化约2倍。这些数据表明，肿瘤血管的渗透选择性低于正常血管，可能是由于血管壁上的大孔所致。大分子的传输似乎受到通过这些孔的扩散的限制。通过观察直径为 100-600 nm 的空间稳定脂质体的经血管运输来估计孔的截止尺寸。我们发现模型中的肿瘤血管可渗透直径达 400 nm 的脂质体，这表明孔的截止尺寸在直径 400 至 600 nm 之间。
Molecular size is one of the key determinants of transvascular transport of therapeutic agents in tumors. However, there are no data in the literature on the molecular size dependence of microvascular permeability in tumors. Therefore, we measured microvascular permeability to various macromolecules in the human colon adenocarcinoma LS174T transplanted in dorsal skin chambers in severe combined immunodeficient mice. These molecules were fluorescently labeled and injected i.v. into mice. The microvascular permeability was calculated from the fluorescence intensity measured by the intravital fluorescence microscopy technique. The value of permeability varied approximately 2-fold in the range of molecular weight from 25,000 to 160,000. These data indicate that tumor vessels are less permselective than normal vessels, presumably due to large pores in the vessel wall. The transport of macromolecules appears to be limited by diffusion through these pores. The cutoff size of the pores was estimated by observations of transvascular transport of sterically stabilized liposomes of 100-600 nm in diameter. We found that tumor vessels in our model were permeable to liposomes of up to 400 nm in diameter, suggesting that the cutoff size of the pores is between 400 and 600 nm in diameter.