Development of a spheroid model to simulate drug penetration in solid tumors

The two main types of tissue culture models are commonly divided into two-dimensional (2D) models and three-dimensional (3D) models.

Various critical aspects of physiological conditions are not addressed in the 2D models, including the extracellular environment, adhesion proteins, and the configuration of micro-epoxy in 3D. The current existing 3D models have difficulties in monitoring drug diffusion and in-tumor drug sensitivity.

Our approach to overcome these challenges was to develop a robust, uniform and highly reproducible 3D co-culture sphere inside a spheroid model, with a constant spheroid size, allowing one spheroid per well, with a fluorescent core. The 3D spheroid model as presented in this research consists of liver cancer cells in the outer spheroid structure and green fluorescent protein (GFP) expressing fibroblast cells in its core. Its three-dimensional structure provides a good simulation of an in-vivo solid tumor and by monitoring the mean fluorescence intensity (MFI) given by the GFP expressed from the fibroblast cells core, we were able to screen anti-cancer drugs and evaluate drug penetration and diffusion time inside the spheroid.

The described model was tested with both free drugs and drug-carrying nanoparticles. Our preliminary results show a decrease in GFP fluorescence as a function of drug concentration and time.