Three-Dimensional Microtissue Assay for High-Throughput Cytotoxicity of Nanoparticles

    Authors

    Y. Luo; C. M. Wang; M. Hossain; Y. Qiao; L. Y. Ma; J. C. An;M. Su

    Comments

    Authors: contact us about adding a copy of your work at STARS@ucf.edu

    Abbreviated Journal Title

    Anal. Chem.

    Keywords

    CDTE QUANTUM DOTS; IN-VIVO TOXICITY; DIFFERENTIAL CYTOTOXICITY; PULMONARY TOXICITY; CELLULAR TOXICITY; CARBON NANOTUBES; DRUG-DELIVERY; PEG; VITRO; CELLS; Chemistry, Analytical

    Abstract

    Traditional in vitro nanotoxicity researches are conducted on cultured two-dimensional (2D) monolayer cells and thereby cannot reflect organism response to nanoparticle toxicities at tissue levels. This paper describes a new, high-throughput approach to test in vitro nanotoxicity in three-dimensional (3D) microtissue array, where microtissues are formed by seeding cells in nonsticky microwells, and cells are allowed to aggregate and grow into microtissues with defined size and shape. Nanoparticles attach and diffuse into microtissues gradually, causing radial cytotoxicity among cells, with more cells being killed on the outer layers of the microtissue than inside. Three classical toxicity assays [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT), glucose-6-phosphate dehydrogenase (G6DP), and calcein AM and ethidium homodimer (calcein AM/EthD-1)] have been adopted to verify the feasibility of the proposed approach. Results show that the nanotoxicities derived from this method are significantly lower than that from traditional 2D cultured monolayer cells (p < 0.05). Equipped with a microplate reader or a microscope, the nanotoxicity assay could be completed automatically without transferring the microtissue, ensuring the reliability of toxicity assay. The proposed approach provides a new strategy for high-throughput, simple, and accurate evaluation of nanoparticle toxicities by combining 3D microtissue array with a panel of classical toxicity assays.

    Journal Title

    Analytical Chemistry

    Volume

    84

    Issue/Number

    15

    Publication Date

    1-1-2012

    Document Type

    Article

    Language

    English

    First Page

    6731

    Last Page

    6738

    WOS Identifier

    WOS:000307159200066

    ISSN

    0003-2700

    Share

    COinS