Systematic nanoparticle diffusivity estimation using multicellular tumor spheroid model

Despite the vast potential of nanoparticles in anticancer therapies, the method of evaluating nanoparticle penetration within specific tumors is neither standardized nor mainstream. Multicellular tumor spheroids have been established as a popular model for in vitro screening of nanoparticles; however, their utility would be expanded considerably by improved quantification of nanoparticle diffusivity. This paper outlines a method to accurately estimate the diffusivity of nanoparticles in multicellular tumor spheroids using an unsteady-state diffusion based simulation model. This simulation model has been shown to accurately estimate diffusivity using synthetic data. Validation of the model's use in drug-delivery studies is accomplished through the high throughput creation of consistent tumor spheroids, introduction of fluorescently-labeled nanoparticles into the engineered tumors, and image processing of spheroid samples. Once validated, this system will allow researchers to efficiently quantify diffusivity for their nanoparticle drug delivery systems.