Interaction of Particles with Tumor Tissue Using Ex Vivo Cellular Model

Predicting the biodistribution and penetration of particle-based drug delivery systems in tumor tissues is highly challenging. Most studies in vitro investigating the interactions of particles with cells use monolayers; however, only minimal information can be gained using existing cellular models in a single cell setup. To provide an available and more reliable physiological model, it is critical to simulate cancer tissue characteristics including all its complexity to obtain a similar response in a cell culture model. Multicellular cancer spheroids can be developed as a predictive tool to study cell-particle interactions and their capacity for tissue penetration. Here we investigated the engulfment of different sized particles by cancer cells in a 3D culture comprised from pancreatic cell lines or patient-derived tumor tissue cells. Using advanced imaging techniques, we were able to detect and evaluate the penetration capacity of different sized particles ranging from 0.5 to 2 micron in size. Our results clearly show the variation in penetration of particles with a different size in the same 3D ex vivo tissue, and differences between various tumors using the same particle size. We propose to utilize spheroids as a useful model for studying particle diffusion in tissues and for tissue biodistribution.