Institute for Micromanufacturing, Louisiana Tech University, Ruston, LA 71272, United States; Biomedical Engineering, Louisiana Tech University, Ruston, LA 71272, United States.
Comput Methods Programs Biomed. 2013 Oct;112(1):58-68. doi: 10.1016/j.cmpb.2013.06.011. Epub 2013 Jul 18.
Determining the factors that influence the delivery of sub-micron particles to tumors and understanding the relative importance of each of these factors is fundamental to the optimization of the particle delivery process. In this paper, a model that combines random walk with the pressure driven movement of nanoparticles in a tumor vasculature is presented. Nanoparticle movement in a cylindrical tube with dimensions similar to the tumor's blood capillary with a single pore is simulated. Nanoparticle velocities are calculated as a pressure driven flow over imposed to Brownian motion. The number and percentage of nanoparticles leaving the blood vessel through a single pore is obtained as a function of pore size, nanoparticle size and concentration, interstitial pressure, and blood pressure. The model presented here is able to determine the importance of these controllable parameters and thus it can be used to understand the process and predict the best conditions for nanoparticle-based treatment. The results indicate that the nanoparticle delivery gradually increases with pore size and decreases with nanoparticle size for tumors with high interstitial fluid pressure (in this work we found this behavior for head and neck carcinoma and for metastatic melanoma with interstitial pressures of 18mmHg and 19mmHg, respectively). For tumors with lower interstitial fluid pressure (rectal carcinoma with 15.3mmHg) however, delivery is observed to have little sensitivity to particle size for almost the entire nanoparticle size range. Though an increase in nanoparticle concentration increases the number of nanoparticles being delivered, the efficiency of the delivery (percentage of nanoparticles delivered) is found to remain closely unaffected.
确定影响亚微米颗粒输送到肿瘤的因素，并了解这些因素的相对重要性，对于优化颗粒输送过程至关重要。在本文中，提出了一种将随机漫步与纳米颗粒在肿瘤脉管系统中的压力驱动运动相结合的模型。模拟了与肿瘤毛细血管尺寸相似的具有单个孔的圆柱形管中纳米颗粒的运动。纳米颗粒的速度通过对布朗运动施加压力驱动流来计算。作为孔径、纳米颗粒尺寸和浓度、间质压力和血压的函数，获得了通过单个孔离开血管的纳米颗粒的数量和百分比。本文提出的模型能够确定这些可控参数的重要性，因此可以用于理解该过程并预测基于纳米颗粒的治疗的最佳条件。结果表明，对于具有高间质流体压力的肿瘤（在这项工作中，我们分别发现了头颈部癌和转移性黑色素瘤的这种行为，其间质压力分别为 18mmHg 和 19mmHg），随着孔径的增大，纳米颗粒的输送逐渐增加，而随着纳米颗粒尺寸的增大而减小。然而，对于间质流体压力较低的肿瘤（间质压力为 15.3mmHg 的直肠癌），输送对颗粒尺寸的敏感性很小，几乎在整个纳米颗粒尺寸范围内都是如此。虽然纳米颗粒浓度的增加会增加输送的纳米颗粒数量，但输送的效率（输送的纳米颗粒百分比）发现几乎不受影响。
