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.

Graphical abstract

中文翻译：

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由于轻度全身热疗后导水率增加或淋巴功能恢复，增强金纳米颗粒输送至 PC3 肿瘤的理论评估

本研究的目的是研究热疗诱导的水力传导率和淋巴功能的改善对肿瘤 IFP 减少和纳米颗粒输送到 PC3 肿瘤的影响。我们开发了一种肿瘤中纳米粒子传输的理论模型，其中包含 Starling 定律、达西定律、瞬态对流和化学物质在多孔介质中的扩散，以及纳米粒子在肿瘤中的积累。结果表明，这两种机制都可以有效地将肿瘤中心的 IFP 从未加热的对照中的 1600 Pa 降低到全身加热的肿瘤中的 800 Pa。IFP 减少不仅提高了肿瘤中的纳米颗粒浓度，而且还导致肿瘤中的纳米颗粒浓度比没有加热的对照更均匀。由于肿瘤中心的 IFP 减少和/或局部血液灌注增加，与没有加热的对照相比，肿瘤中累积的纳米颗粒的最终量增加了 35-95% 以上。我们得出结论，在我们的体内实验研究中观察到，水力传导率的增加和淋巴功能的恢复是导致 IFP 减少和 PC3 肿瘤中纳米颗粒沉积增强的可能机制。

图形概要