title: In vitro toxicity testing of nanoparticles in 3D cell culture.
abstract: Common 2D cell cultures do not adequately represent the functions of 3D tissues that have extensive cell-cell and cell-matrix interactions, as well as markedly different diffusion/transport conditions. Hence, testing cytotoxicity in 2D cultures may not accurately reflect the actual toxicity of nanoparticles (NPs) and other nanostructures in the body. To obtain more adequate and detailed information about NP-tissue interactions, we here introduce a 3D-spheroid-culture-based NP toxicology testing system. Hydrogel inverted colloidal crystal (ICC) scaffolds are used to create a physiologically relevant and standardized 3D liver tissue spheroid model for in vitro assay application. Toxicity of CdTe and Au NPs are tested in both 2D and 3D spheroid cultures. The results reveal that NP toxic effects are significantly reduced in the spheroid culture when compared to the 2D culture data. Tissue-like morphology and phenotypic change are identified to be the major factors in diminishing toxicity. Acting as an intermediate stage bridging in vitro 2D and in vivo, our in vitro 3D cell-culture model would extend current cellular level cytotoxicity to the tissue level, thereby improving the predictive power of in vitro NP toxicology.
authors.affiliation: Department of Biomedical Engineering, Chemical Engineering, Material Science and Engineering, University of Michigan, Ann Arbor, 48109, USA.
authors.forename: Jungwoo
authors.initials: J
authors.lastname: Lee
authors.forename: G Daniel
authors.initials: GD
authors.lastname: Lilly
authors.forename: R Christopher
authors.initials: RC
authors.lastname: Doty
authors.forename: Paul
authors.initials: P
authors.lastname: Podsiadlo
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Kotov
mesh_terms: D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003102:Colloids; D003460:Crystallization; D005562:Formazans; D006801:Humans; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D053758:Nanoparticles / Q000633:toxicity*; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D013778:Tetrazolium Salts; D018675:Toxicity Tests; D014407:Tumor Cells, Cultured
chemical_list: D003102:Colloids; D005562:Formazans; D013778:Tetrazolium Salts; C079782:MTT formazan; D007770:L-Lactate Dehydrogenase