Advances in the study of spheroids as versatile models to evaluate biological interactions of inorganic nanoparticles

Spheroids are in vitro three-dimensional multicellular microstructures able to mimic the biological microenvironment, including the complexity of tumor architecture. Therefore, results closer to those expected for in vivo organisms can be reached using spheroids compared to the cell culture monolayer model. Inorganic nanoparticles (NPs) have also been playing relevant roles in the comprehension of biological processes. Moreover, they have been probed as novel diagnostic and therapeutical nanosystems. In this context, in this review, we present applications, published in the last five years, which show that spheroids can be versatile models to study and evaluate biological interactions involving inorganic NPs. Applications of spheroids associated with (i) basic studies to assess the penetration profile of nanostructures, (ii) the evaluation of NP toxicity, and (iii) NP-based therapeutical approaches are described. Fundamentals of spheroids and their formation methods are also included. We hope that this review can be a reference and guide future investigations related to this interesting three-dimensional biological model, favoring advances to Nanobiotechnology. [Display omitted] •Spheroids are 3D models that can mimic better in vivo tissues than 2D cell culture.•Spheroids have been applied as a useful model to study the biomedical potential of inorganic NPs.•Different methods of spheroid preparation are comprehensively reviewed.•The use of spheroids to study basic interaction, toxicity, and therapeutics involving inorganic NPs are described.•Spheroids can support advances in the development of inorganic NPs for life sciences.