Now showing 1 - 2 of 2
  • Publication
    Experimental and theoretical approach to comparative nanoparticle and small molecule intracellular import, trafficking, and export
    Central to understanding how nanoscale objects interact with living matter is the need for reproducible and verifiable data that can be interpreted with confidence. Likely this will be the basis of durable advances in nanomedicine and nanomedical safety. To develop these fields, there is also considerable interest in advancing the first generation of theoretical models of nanoparticle (NP) uptake into cells, and NP biodistribution in general. Here we present an uptake study comparing the outcomes for free molecular dye and NPs labeled with the same dye. A simple flux-based approach is presented to model NP uptake. We find that the intracellular NP concentration grows linearly in time, and that the uptake is essentially irreversible, with the particles accumulating in lysosomes. A wide range of practical challenges, from labile dye release to NP aggregation and the need to account for cell division, are addressed to ensure that these studies yield meaningful kinetic information.
    Scopus© Citations 271  1543
  • Publication
    Quantitative assessment of the comparative nanoparticle-uptake efficiency of a range of cell lines
    Interest continues to grow in the possibility of understanding the mechanism(s) of nanoparticle-cell interactions. At present there is little knowledge, and essentially no understanding, of the relevant length and time scales for nanoparticle-intracellular entry, and localization within cells, and the cell-specificity of nanoparticle uptake and localisation. We have investigated here the effect of particle size on the in vitro intracellular uptake of model fluorescent carboxyl-modified polystyrene nanoparticles in various cell lines commonly used for uptake studies. A range of micro- and nanoparticles of defined sizes (40 nm to 2 μm)were incubated with a series of cell types, including HeLa and A549 epithelial cells, 1321N1 astrocytes, HCMEC D3 endothelial cells and murine RAW 264.7 macrophages. Techniques such as confocal microscopy and flow cytometry were used to study particle uptake and sub-cellular localisation, making significant efforts to ensure reproducibility in a semi-quantitative approach. The results indicated that internalization of (nano)particles is highly size dependent for all cell lines studied and that the kinetics of uptake for the same nanoparticle varies in the different cell types. Interestingly, even cells non specialized for phagocytosis were able to internalize the larger nanoparticles. Intracellular uptake of all sizes of (nano)particles was observed to be the highest in RAW 264.7 cells (a specialized phagocytic cell line) and the lowest in the HeLa cells. Results suggests that (nano)particle uptake might not follow commonly defined size limits for uptake processes and highlights the variability of uptake kinetics for the same material in different cell types. These conclusions have important implications for the assessment of the safety of nanomaterials and potential biomedical applications of nanoparticles.
    Scopus© Citations 212  2192