Testingin vitrotoxicity of nanoparticles in 3D cell culture with various extracellular matrix scaffold

Abstract

Nanomaterials are used in a variety of fields and toxicity assessment is paramount for their development and application. Although most toxicity assessments have been performed in 2D (2-Dimensional) cell culture, the inability to adequately replicate the in vivo environment and toxicity is a limitation. To overcome the limitation, a 3D (3-Dimensional) cell culture method has been developed to make an environment closer to an in vivo system. In this study, 20 nm SiO2 nanoparticles were dispersed in serum-containing (SC) and serum-free (SF) media to compare 2D cell culture and 3D cell culture toxicity. The cells were subjected to a 3D cell culture method in which HepG2, a human-derived liver cancer cell line, was mixed on a scaffold. We found that nanoparticles induced toxicity in 2D cell culture, but toxicity was not observed in 3D cell culture similar to in vivo environment. However, differences in toxicity were observed between the three types of scaffolds in the absence of serum as the number of cells decreased.

Nanoparticles‐induced potential toxicity on human health: Applications, toxicity mechanisms, and evaluation models

“…The direct addition of higher concentrations of NPs to cells has a stronger effect on cells than prediluting and mixing NPs with the medium before adding them to cells, but the mechanisms involved are not obvious, so the evaluation of NPs at the cellular level requires more data to support the view. Due to the limitations of the two‐dimensional cell culture model, one study also compared the difference in toxicity between a three‐dimensional cell model with SNPs cultured in an extracellular matrix and a two‐dimensional HepG2 cell culture model, and in agreement with expectations, the results were different, with more severe damage in the two‐dimensional cell model 355 …”

“…Due to the limitations of the two-dimensional cell culture model, one study also compared the difference in toxicity between a three-dimensional cell model with SNPs cultured in an extracellular matrix and a two-dimensional HepG2 cell culture model, and in agreement with expectations, the results were different, with more severe damage in the two-dimensional cell model. 355 While in vitro cellular assays can help assess the toxicity of nanomaterials, they may not be able to account for the complexities of pharmacokinetics, organ toxicity, and preclinical and clinical conditions. Additionally, the results can differ significantly from study to study and laboratory to laboratory.…”

“…Due to the limitations of the two‐dimensional cell culture model, one study also compared the difference in toxicity between a three‐dimensional cell model with SNPs cultured in an extracellular matrix and a two‐dimensional HepG2 cell culture model, and in agreement with expectations, the results were different, with more severe damage in the two‐dimensional cell model. 355 …”

Exploring the Impact of Nanoparticle Stealth Coatings in Cancer Models: From PEGylation to Cell Membrane-Coating Nanotechnology

“…It has been extensively demonstrated how the toxic effects of NPs are significantly reduced in cultured 3D models, such as cell spheroids, compared to monolayer culture data . Furthermore, ECM and stromal cells can alter the accessibility of NPs to the tumor and their internalization in tumor cells as they generate a physical obstacle and trigger biological changes in the tumor that can be a limiting factor in the efficacy of these treatments . These effects can be elucidated in vitro using three-dimensional models encapsulated in hydrogels, which more closely replicate the in vivo cellular uptake of NPs. , Collagen type I was employed to generate an ECM-derived hydrogel as it is the most abundant structural protein in breast cancer tissues and plays a fundamental role in tumor progression and drug resistance .…”

“…52 These effects can be elucidated in vitro using three-dimensional models encapsulated in hydrogels, which more closely replicate the in vivo cellular uptake of NPs. 50,52 Collagen type I was employed to generate an ECM-derived hydrogel as it is the most abundant structural protein in breast cancer tissues and plays a fundamental role in tumor progression and drug resistance. 53 The behavior of the prepared NPs was analyzed in multicellular spheroids of MCF-7 and FBs embedded in a collagen type-I hydrogel to study their effect in a biomimetic environment comprising the ECM.…”