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Interactions of engineered nanomaterials in physiological media and implications for in vitro dosimetry.

ABSTRACT: In vitro toxicity assays are efficient and inexpensive tools for screening the increasing number of engineered nanomaterials (ENMs) entering the consumer market. However, the data produced by in vitro studies often vary substantially among different studies and from in vivo data. In part, these discrepancies may be attributable to lack of standardisation in dispersion protocols and inadequate characterisation of particle-media interactions which may affect the particle kinetics and the dose delivered to cells. In this study, a novel approach for preparation of monodisperse, stabilised liquid suspensions is presented and coupled with a numerical model which estimates delivered dose values. Empirically derived material- and media-specific functions are presented for each media-ENM system that can be used to convert administered doses to delivered doses. The interactions of ENMs with a variety of physiologic media were investigated and the importance of this approach was demonstrated by in vitro cytotoxicity assays using THP-1 macrophages.

SUBMITTER: Cohen J

PROVIDER: S-EPMC4479135 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Interactions of engineered nanomaterials in physiological media and implications for in vitro dosimetry.

Cohen Joel J Deloid Glen G Pyrgiotakis Georgios G Demokritou Philip P

Nanotoxicology 20120320 4

In vitro toxicity assays are efficient and inexpensive tools for screening the increasing number of engineered nanomaterials (ENMs) entering the consumer market. However, the data produced by in vitro studies often vary substantially among different studies and from in vivo data. In part, these discrepancies may be attributable to lack of standardisation in dispersion protocols and inadequate characterisation of particle-media interactions which may affect the particle kinetics and the dose deli ...[more]

PMID: 22393878

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Project description:BackgroundThere is a great need for screening tools capable of rapidly assessing nanomaterial toxicity. One impediment to the development of reliable in vitro screening methods is the need for accurate measures of cellular dose. We present here a methodology that enables accurate determination of delivered to cell dose metrics. This methodology includes (1) standardization of engineered nanomaterial (ENM) suspension preparation; (2) measurement of ENM characteristics controlling delivery to cells in culture; and (3) calculation of delivered dose as a function of exposure time using the ISDD model. The approach is validated against experimentally measured doses, and simplified analytical expressions for the delivered dose (Relevant In Vitro Dose (RID)f function) are derived for 20 ENMs. These functions can be used by nanotoxicologists to accurately calculate the total mass (RIDM), surface area (RIDSA), or particle number (RIDN) delivered to cells as a function of exposure time.ResultsThe proposed methodology was used to derive the effective density, agglomerate diameter and RID functions for 17 industrially-relevant metal and metal oxide ENMs, two carbonaceous nanoparticles, and non-agglomerating gold nanospheres, for two well plate configurations (96 and 384 well plates). For agglomerating ENMs, the measured effective density was on average 60% below the material density. We report great variability in delivered dose metrics, with some materials depositing within 24 hours while others require over 100 hours for delivery to cells. A neutron-activated tracer particle system was employed to validate the proposed in vitro dosimetry methodology for a number of ENMs (measured delivered to cell dose within 9% of estimated).ConclusionsOur findings confirm and extend experimental and computational evidence that agglomerate characteristics affect the dose delivered to cells. Therefore measurement of these characteristics is critical for effective use of in vitro systems for nanotoxicology. The mixed experimental/computational approach to cellular dosimetry proposed and validated here can be used by nanotoxicologists to accurately calculate the delivered to cell dose metrics for various ENMs and in vitro conditions as a function of exposure time. The RID functions and characterization data for widely used ENMs presented here can together be used by experimentalists to design and interpret toxicity studies.

Dataset Information

Interactions of engineered nanomaterials in physiological media and implications for in vitro dosimetry.

Publications

Interactions of engineered nanomaterials in physiological media and implications for in vitro dosimetry.

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