Scaling rules for diffusive drug delivery in tumor and normal tissues

被引:145
作者
Baish, James W. [1 ,2 ]
Stylianopoulos, Triantafyllos [3 ,4 ]
Lanning, Ryan M. [3 ,4 ]
Kamoun, Walid S. [3 ,4 ]
Fukumura, Dai [3 ,4 ]
Munn, Lance L. [3 ,4 ]
Jain, Rakesh K. [3 ,4 ]
机构
[1] Bucknell Univ, Dept Mech, Lewisburg, PA 17837 USA
[2] Bucknell Univ, Dept Biomed Engn, Lewisburg, PA 17837 USA
[3] Harvard Univ, Sch Med, Boston, MA 02114 USA
[4] Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA
关键词
antiangiogenesis; cancer; fractal dimension; percolation; transport; VASCULAR NORMALIZATION; ANTIANGIOGENIC THERAPY; PRESSURE; GROWTH; MICROSCOPY; CANCER; MODEL; ANGIOGENESIS; ARCHITECTURE; BRAIN;
D O I
10.1073/pnas.1018154108
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Delivery of blood-borne molecules and nanoparticles from the vasculature to cells in the tissue differs dramatically between tumor and normal tissues due to differences in their vascular architectures. Here we show that two simple measures of vascular geometry-delta(max) and lambda-readily obtained from vascular images, capture these differences and link vascular structure to delivery in both tissue types. The longest time needed to bring materials to their destination scales with the square of delta(max), the maximum distance in the tissue from the nearest blood vessel, whereas., a measure of the shape of the spaces between vessels, determines the rate of delivery for shorter times. Our results are useful for evaluating how new therapeutic agents that inhibit or stimulate vascular growth alter the functional efficiency of the vasculature and more broadly for analysis of diffusion in irregularly shaped domains.
引用
收藏
页码:1799 / 1803
页数:5
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