Extension of a multiphase tumour growth model to study nanoparticle delivery to solid tumours

Abstract

One of the main challenges in increasing the efficacy of conventional chemotherapeutics is the fact that they do not reach cancerous cells at a sufficiently high dosage. In order to remedy this deficiency, nanoparticle-based drugs have evolved as a promising novel approach to more specific tumour targeting. Nevertheless, several biophysical phenomena prevent the sufficient penetration of nanoparticles in order to target the entire tumour. We therefore extend our vascular multiphase tumour growth model, enabling it to investigate the influence of different biophysical factors on the distribution of nanoparticles in the tumour microenvironment. The novel model permits the examination of the interplay between the size of vessel-wall pores, the permeability of the blood-vessel endothelium and the lymphatic drainage on the delivery of particles of different sizes. Solid tumours develop a non-perfused core and increased interstitial pressure. Our model confirms that those two typical features of solid tumours limit nanoparticle delivery. Only in case of small nanoparticles is the transport dominated by diffusion, and particles can reach the entire tumour. The size of the vessel-wall pores and the permeability of the blood-vessel endothelium have a major impact on the amount of delivered nanoparticles. This extended in-silico tumour growth model permits the examination of the characteristics and of the limitations of nanoparticle delivery to solid tumours, which currently complicate the translation of nanoparticle therapy to a clinical stage.