Simulation study of the effects of interstitial fluid pressure and blood flow velocity on transvascular transport of nanoparticles in tumor microenvironment.

Gao, Yan; Shi, Yanbin; Fu, Mengguang; Feng, Yihua; Lin, Guimei; Kong, Deyin; Jiang, Bo

BACKGROUND AND OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.