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

SIMPLE SUMMARY: Nanoparticle radiosensitizers can be used to increase the efficacy of radiotherapy. In this work a multiscale computational model has been developed to assess the distribution of nanoparticles during and after intratumoural injection into a realistic tumour. The aim of the study is to assess how particle surface charge and injection location can affect the distribution of nanoparticles within the tumour, with the optimal result being a uniform concentration across the tumour. This work aims to aid the development of radiosensitizers and guide clinical trials. 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.