期刊
BIOPHYSICAL JOURNAL
卷 115, 期 6, 页码 1103-1115出版社
CELL PRESS
DOI: 10.1016/j.bpj.2018.07.038
关键词
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类别
资金
- National Institutes of Health [U54 CA 151459-02]
- Stanford Graduate Engineering Fellowship
- Stanford Center for Cancer Nanotechnology Excellence Focused on Therapy Response pilot program [U54-CA119367]
- Hana Jabsheh initiative
- National Science Foundation-Major Research Instrumentation award [0960306]
- Department of Defense through the National Defense Science & Engineering Graduate Fellowship program
- K99/R00 award [K99 CA160764]
- National Institutes of Health grant for a Center for Systems Biology [U54-CA209971]
- Ben and Catherine Ivy Foundation
- Stanford Bio-X Interdisciplinary Initiatives Program grant
- National Science Foundation [ECCS-1542152]
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [0960306] Funding Source: National Science Foundation
In modern cancer treatment, there is significant interest in studying the use of drug molecules either directly injected into the bloodstream or delivered by nanoparticle (NP) carriers of various shapes and sizes. During treatment, these carriers may extravasate through pores in the tumor vasculature that form during angiogenesis. We provide an analytical, computational, and experimental examination of the extravasation of point particles (e.g., drug molecules) and finite-sized spheroidal particles. We study the advection-diffusion process in a model microvasculature, consisting of a shear flow over and a pressure-driven suction flow into a circular pore in a flat surface. For point particles, we provide an analytical formula S(kappa,P,Q) approximate to (1/kappa + pi/4(1 + 0.3959P(1/2))(2/3)))(-1) + 2PQ for the dimensionless Sherwood number S, i.e., the extravasation rate, in terms of the pore entry resistance (Damkohler number kappa), the shear rate (Peclet number P) , and the suction flow rate (suction strength Q) . Brownian dynamics (BD) simulations verify this result, and our simulations are then extended to include finite-sized NPs, in which no analytical solutions are available. BD simulations indicate that particles of different geometries have drastically different extravasation rates in different flow conditions. In general, extreme aspect ratio particles provide a greater flux through the pore because of favorable alignment with streamlines entering the pore and less hindered interaction with the pore. We validate the BD simulations by measuring the in vitro transport of both bacteriophage MS2 (a spherical NP) and free dye (a model drug molecule) across a porous membrane. Despite their vastly different sizes, BD predicts S = 8.53 E-4 and S = 27.6 E - 4, and our experiments agree favorably, with S-exp = 10.6 E-4 +/- 1.75 E-4 and S-exp = 16.3 E-4 +/- 3.09 E - 4, for MS2 and free dye, respectively, thus demonstrating the practical utility of our simulation framework.
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