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.

Automated summary

Spheroids are three-dimensional multicellular microstructures that can replicate the complexity of the biological microenvironment and tumor architecture. Compared to traditional cell culture methods, spheroids provide more accurate results that resemble in vivo organisms. In addition, inorganic nanoparticles have been proven to be valuable tools for understanding biological processes and have potential applications in diagnostics and therapeutics. This review highlights the versatility of spheroids in studying biological interactions involving inorganic nanoparticles, including penetration profiles, toxicity evaluation, and therapeutical approaches.