Multiscale Modelling of Nanoparticle Distribution in a Realistic Tumour Geometry Following Local Injection

Abstract

Radiosensitizers have proven to be an effective method of improving radiotherapy outcomes, with the distribution of particles being a crucial element to delivering optimal treatment outcomes due to the short range of effect of these particles. Here we present a computational model for the transport of nanoparticles within the tumour, whereby the fluid velocity and particle deposition are obtained and used as input into the convection-diffusion equation to calculate the spatio-temporal concentration of the nanoparticles. The effect of particle surface charge and injection locations on the distribution of nanoparticle concentration within the interstitial fluid and deposited onto cell surfaces is assessed. The computational results demonstrate that negatively charged particles can achieve a more uniform distribution throughout the tumour as compared to uncharged or positively charged particles, with particle volume within the fluid being 100% of tumour volume and deposited particle volume 44.5%. In addition, varying the injection location from the end to the middle of the tumour caused a reduction in particle volume of almost 20% for negatively charged particles. In conclusion, radiosensitizing particles should be negatively charged to maximise their spread and penetration within the tumour. Choosing an appropriate injection location can further improve the distribution of these particles.

A Novel Experimental Approach to Understand the Transport of Nanodrugs

“…The mass loss, however, shows a slight decrease in this size range, which implies that competing diffusion and sedimentation mechanisms control the nanodrug transport in this size regime. The decrease in deposition for the 302 nm sized nanodrugs can be explained in terms of an increase in diffusivity of the combined nanodrug as compared to the zinc oxide nanodrug, as seen from the trend in the velocity profile [33,39,40,49]. Surface properties such as the surface charge of the nanodrugs also have a major influence on their transport.…”

“…Diffusivity of spherical particles in a fluid is an inverse function of particle diameter, based on the Stokes-Einstein equation. Particles with high diffusivity exhibit a low deposition rate [33]. The mass loss of nanodrugs during the flow through channels 1 and 2 can be attributed to the deposition of particles on the walls of the flow channels and therefore, provide a measure of the deposition rate of the nanodrugs.…”

“…To this end, different computational approaches have been reported for nanodrugs in an effort to translate the preclinical stage efficacy to clinical trials [33][34][35][36][37]. For example, Moreno-Chaparro et al, reported that the nanoparticle's shape plays a key role in the transport behavior for surface functionalized nanoparticles [38].…”