Effect of nanoparticle size, magnetic intensity, and tumor distance on the distribution of the magnetic nanoparticles in a heterogeneous tumor microenvironment

Abstract

Tumor microenvironment involves physical parameters that impede the transport of therapeutic agents and create an abnormal extracellular matrix (ECM) at the region with an elevated interstitial fluid pressure (IFP). This is the main reason that the chemotherapy drug agents could not fully penetrate the solid tumors. To overcome this resistance, drug-coated magnetic nanoparticle (MNP) had been proposed as a therapeutic agent affected by an external magnetic force. Three variables as the MNP’s size, magnetic field intensity, and the tumor-magnet distance are proposed to see their effects on the distribution of the drugs to the tumor tissue. A micro-scale computational domain is assumed as the normal and tumor tissues with the discrete microvessels. The results determine a moderate effect on the drug penetration to the tumor tissue by the magnetic field and size variations. This moderate effect is due to the consequent of the high density of ECM and high amount of IFP leading only a 36% increase in the drug penetration to the tumor tissue with a 10 nm MNP and under the 2.5 T magnetic field intensity. While, a slight percent increase about 11% is obtained from 0.6 T to 2.5 T. We conclude that the dense ECM, high IFP, and the existence of microvessels have negative effects on the systemic delivery of the MNP distribution leading to a low impact of Magnetic field on the MNPs’ penetration. Therefore, The systemic drug delivery of MNP under the magnetic field has a lower effect in comparison to local drug delivery of MNPs to the homogenous solid tumors. However, the convection rate in the tumor tissue shows a percent increase in the rate of drug distribution to the tumor tissue. The size and the magnetic field are the two most promised parameters for improving the convection term in the tumor region. the finding of this study can help to better understanding the magnetic effects on the distribution rate of MNP to the solid tumor and to overcome the tumor microenvironmet barriers for better drug efficacy.