Department of Mechanical Engineering, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD, 21250, USA.
Med Biol Eng Comput. 2021 Feb;59(2):301-313. doi: 10.1007/s11517-020-02308-4. Epub 2021 Jan 11.
The objective of this study is to investigate the effect of hyperthermia-induced improvement of hydraulic conductivity and lymphatic function on both tumoral IFP reduction and nanoparticle delivery to PC3 tumors. We developed a theoretical model for nanoparticle transport in a tumor incorporating Starling's law, Darcy's law, transient convection, and diffusion of chemical species in porous media, and nanoparticle accumulation in tumors. Results have shown that both mechanisms were effective to decrease the IFP at the tumor center from 1600 Pa in the control without heating to 800 Pa in tumors with whole body heating. IFP reductions not only elevate the nanoparticle concentration in the tumor, but also result in a more uniform nanoparticle concentration in the tumor than that in the control without heating. Due to the IFP reductions at the tumor center and/or local blood perfusion increases, the final amount of accumulated nanoparticles in the tumor increased by more than 35-95% when compared to the control without heating. We conclude that increases in the hydraulic conductivity and recovery of lymphatic functions are possible mechanisms that lead to IFP reductions and enhancement in nanoparticle deposition in PC3 tumors observed in our in vivo experimental studies.
本研究旨在探讨高热诱导的水通透性和淋巴功能改善对肿瘤内间质液压（IFP）降低和纳米颗粒递送至 PC3 肿瘤的影响。我们开发了一个包含 Starling 定律、达西定律、瞬态对流和多孔介质中化学物质扩散以及肿瘤内纳米颗粒积累的理论模型，用于研究纳米颗粒在肿瘤中的输运。结果表明，这两种机制均能有效降低未加热对照组肿瘤中心的 IFP，从 1600 Pa 降低至全身加热组的 800 Pa。IFP 降低不仅提高了肿瘤中的纳米颗粒浓度，而且使肿瘤内纳米颗粒的浓度分布比未加热对照组更加均匀。由于肿瘤中心的 IFP 降低和/或局部血液灌注增加，与未加热对照组相比，肿瘤中累积的纳米颗粒最终增加了 35-95%以上。我们得出结论，水通透性的增加和淋巴功能的恢复是导致我们在体内实验研究中观察到的 IFP 降低和纳米颗粒沉积增强的可能机制。
