Analysis of polymeric nanoparticle properties for siRNA/DNA delivery in a tumor xenograft tissue slice air-liquid interface model

BackgroundClassical two-dimensional (2D) cell culture as a drug or nanoparticle test system only poorly recapitulates in vivo conditions. Animal studies are costly, ethically controversial, and preclude large-scale testing. Methods and ResultsWe established a three-dimensional (3D) tissue slice air-liquid interface (ALI) culture model for nanoparticle testing. We developed an optimized procedure for the reproducible generation of large sets of tissue slices from tumor xenografts that retain their tissue architecture. When used for the analysis of nanoparticles based on chemically modified polyethylenimines (PEIs) to deliver siRNA or DNA, differences in transfection efficacy and cytotoxicity between nanoparticles were observed more clearly than in 2D cell culture. While nanoparticle efficacies between cell culture and the tissue slice model overall correlated, the tissue slice model also identified particularly suitable candidates whose efficacy was underestimated in 2D cell culture and had already been shown in previous in vivo studies. ConclusionThe ex vivo 3D tissue slice ALI culture model is a powerful system that allows the effective evaluation of biological nanoparticle efficacy and biocompatibility in an intact tissue environment. It is comparably inexpensive, time-saving, and follows the 3R principle, while allowing the identification of critical nanoparticle properties and optimal candidates for in vivo applications.

Automated summary

A three-dimensional tissue slice air-liquid interface (ALI) culture model was developed for nanoparticle testing, which showed clearer differences in transfection efficacy and cytotoxicity compared to 2D cell culture. This model allows for the evaluation of biological nanoparticle efficacy and biocompatibility in an intact tissue environment, providing a cost-effective and time-saving alternative.