Gao Yan, Shi Yanbin, Fu Mengguang, Feng Yihua, Lin Guimei, Kong Deyin, Jiang Bo
School of Mechanical & Automotive Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China.
School of Mechanical & Automotive Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China.
Comput Methods Programs Biomed. 2020 Sep;193:105493. doi: 10.1016/j.cmpb.2020.105493. Epub 2020 May 5.
Although nanoparticle preparations have great potential in the treatment of tumors, nanoparticle preparations have not achieved the desired therapeutic effect. The reason is that the abnormal tumor microenvironment prevents nanoparticles from effective concentrating and reaching tumor area. Therefore, it's very necessary to better understand the effect of the abnormal tumor microenvironment on the transvascular transport of nanoparticles to overcome this critical problem.
In this paper, a tumor abnormal vascular-interstitial model was established, and the transvascular transport process of nanoparticles was simulated in the model by computational fluid dynamics (CFD) modeling.
The simulation results showed that the transport efficiency of nanoparticles decreased with increasing interstitial fluid pressure (IFP), and nanoparticles could not cross the blood vessel wall when the IFP approached the blood vessel wall pressure. Interestingly, the transport efficiency of nanoparticles first increased with blood flow velocity, and then decreased with blood flow velocity.
The results showed that with the continuous malignant development of tumors, the ability of nanoparticles to passively diffuse has almost disappeared. The enhanced permeability and retention (EPR) effect of the nanoparticles disappeared with the disappearance of the pressure gradient inside the tumor. These results provided guidance for future research on the vascular transport pathways and mechanisms of nanoparticles.
尽管纳米颗粒制剂在肿瘤治疗中具有巨大潜力,但纳米颗粒制剂尚未达到预期的治疗效果。原因在于异常的肿瘤微环境阻碍纳米颗粒有效富集并到达肿瘤区域。因此,为克服这一关键问题,深入了解异常肿瘤微环境对纳米颗粒跨血管转运的影响非常必要。
本文建立了肿瘤异常血管-间质模型,并通过计算流体动力学(CFD)建模在该模型中模拟纳米颗粒的跨血管转运过程。
模拟结果表明,纳米颗粒的转运效率随间质液压力(IFP)升高而降低,当IFP接近血管壁压力时,纳米颗粒无法穿过血管壁。有趣的是,纳米颗粒的转运效率随血流速度先升高后降低。
结果表明,随着肿瘤的持续恶性发展,纳米颗粒被动扩散的能力几乎消失。随着肿瘤内部压力梯度的消失,纳米颗粒的增强渗透与滞留(EPR)效应也消失了。这些结果为未来纳米颗粒血管转运途径及机制的研究提供了指导。