The response of cells to the exposure of nanomaterials is crucial for determining their safety in their multiple uses; however, the majority of the in vitro experiments use monolayered cell cultures, 2D cell cultures. Multiple studies highlight the different toxicological response, phenotype, metabolism and composition of cells grown on 2D systems (petri dishes, plastic flat surfaces) compared to their growth in 3D systems, a more realistic environment.
3D in vitro cell culture approaches emerged to obtain in vitro cell culture systems that recapitulate realistically and physiologically the environment of cells and to increase the applicability of NPs and drugs. These 3D in vitro approaches also aim at reducing and optimizing the translation of new drugs to the market following the three R notion (Replace, Reduce and Refine).
Here, we have analyzed how the exposed surface of the cells, as well as the environment where cells grow, can influence the interaction and uptake of superparamagnetic iron oxide nanoparticles (SPIONs). We exposed three different cell lines (MDAMB-231, HL60 and bEnd3) grown at different environments with increasing concentrations of SPIONs. We evaluated parameters analyzing the morphological changes of the cell, iron uptake and cell viability. Results showed that upon exposure to SPIONs, cell viability and morphology are more affected when cells are growing in 3D systems, indicating that the increase of exposed surface area of the cells is a strong parameter to take in account when evaluating SPIONs or other materials or drugs. Our results clearly reinforce the use of more realistic environments, such as 3D, for the design of new drug delivery systems.
Maria Milla, Si-Ming Yu, Anna Laromaine
Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Spain
Parametrizing the exposure of superparamagnetic iron oxide nanoparticles in cell cultures at different in vitro environments
Chemical Engineering Journal 340, 173-180 (2018)
Description of cell lines and cell cultures environments used to assess SPIONs in 2D and 3D environments.