Interaction of Particles with Tumor Tissue Using Ex Vivo Cellular Model

Katerina Tischenko Natalie Orehov Ofra Benny
The School of Pharmacy, Faculty of Medicine, The Hebrew University, Israel

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.

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