Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers
Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers
复制标题
DOI：
10.1093/jnci/djj070
复制
发表时间：
2006-03-01
影响因子：
10.3
通讯作者：
Chilkoti, A
中科院分区：
文献类型：
--
作者：
Dreher, MR;Liu, WG;Chilkoti, A
背景：将抗癌治疗剂递送至实体瘤是有问题的。大分子药物载体是一种有吸引力的替代药物递送方法，因为它们似乎靶向肿瘤并且在正常组织中具有有限的毒性。我们研究了分子量如何影响模型大分子药物载体（与荧光团共价连接的葡聚糖）在肿瘤中的积累。方法：我们使用分子量为3.3 kDa至2 MDa的葡聚糖。通过背侧皮肤褶皱窗口室、活体激光扫描共聚焦显微镜和自定义图像分析，在实体瘤中同时测量这些葡聚糖的血管渗透性、积聚和三维渗透。结果如下：增加葡聚糖的分子量在统计学上显著地降低了其血管渗透性大约两个数量级（即，从154 x 10（-7）cm/s，95%置信区间[CI] = 134至174 x 10（-7）cm/s，对于3.3-kDa葡聚糖，到1.7 x 10（-7）cm/s，95%，CI = 0.7至2.6 x 10（-7）cm/s，对于2-MDa葡聚糖; P
Background: Delivery of anticancer therapeutic agents to solid tumors is problematic. Macromolecular drug carriers are an attractive alternative drug delivery method because they appear to target tumors and have limited toxicity in normal tissues. We investigated how molecular weight influences the accumulation of a model macromolecular drug carrier, dextran covalently linked to a fluorophore, in tumors. Methods: We used dextrans with molecular weights from 3.3 kDa to 2 MDa. Vascular permeability, accumulation, and three-dimensional penetration of these dextrans were simultaneously measured in solid tumors via a dorsal skin fold window chamber, intravital laser-scanning confocal microscopy, and custom image analysis. Results: Increasing the molecular weight of dextran statistically significantly reduced its vascular permeability by approximately two orders of magnitude (i.e., from 154 x 10(-7) cm/s, 95% confidence interval [CI] = 134 to 174 x 10(-7) cm/s, for 3.3-kDa dextran to 1.7 x 10(-7) cm/s, 95%, CI = 0.7 to 2.6 x 10(-7) cm/s for 2-MDa dextran; P