Self-assembled Targeting of Cancer Cells by Iron(III)-doped, Silica Nanoparticles - PubMed (original) (raw)

Self-assembled Targeting of Cancer Cells by Iron(III)-doped, Silica Nanoparticles

K K Pohaku Mitchell et al. J Mater Chem B. 2014.

Abstract

Iron(III)-doped silica nanoshells are shown to possess an in vitro cell-receptor mediated targeting functionality for endocytosis. Compared to plain silica nanoparticles, iron enriched ones are shown to be target-specific, a property that makes them potentially better vehicles for applications, such as drug delivery and tumor imaging, by making them more selective and thereby reducing the nanoparticle dose. Iron(III) in the nanoshells can interact with endogenous transferrin, a serum protein found in mammalian cell culture media, which subsequently promotes transport of the nanoshells into cells by the transferrin receptor-mediated endocytosis pathway. The enhanced uptake of the iron(III)-doped nanoshells relative to undoped silica nanoshells by a transferrin receptor-mediated pathway was established using fluorescence and confocal microscopy in an epithelial breast cancer cell line. This process was also confirmed using fluorescence activated cell sorting (FACS) measurements that show competitive blocking of nanoparticle uptake by added holo-transferrin.

Keywords: Silica; nanoparticles; nanoshells; self-targeting; transferrin.

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Figures

Figure 1

Figure 1

Scanning electron microscopy image of 100 nm Fe(III)-doped nanoshells before dispersion. The image shows the morphology of the nanoshells. The scale bar in the lower left is 500 nm.

Figure 2

Figure 2

Fluorescence microscopy images of a cell adhesion/ endocytosis experiment with MDA-MB-231 epithelial breast cancer cells. The top row of images (a-d) show that 100 nm plain silica nanoshells are only minimally taken up by the cells regardless of the nanoshell concentration. Images e-h show that as the concentration of iron(III)-doped, silica nanoshells is increased, cellular uptake increases. The scale bar in the lower right corner of all images is 25 microns.

Figure 3

Figure 3

Confocal microscopy images of 100 nm plain silica (top) and Fe(III)-doped silica (lower panels) nanoshell uptake by MDA-MB-231 cells. The images shown are for three successive slices of the cell separated by 1 micron within the cells. The top row images are for cells incubated with the plain silica nanoshells at 100 ug/ml. The Fe(III)-doped, silica nanoshells (bottom, also 100 ug/ml) can be seen in similar positions in all three images indicating the nanoshells are within the cell. All scale bars in the images are 25 microns.

Figure 4

Figure 4

Fluorescence microscopy images of bovine holoTf blocking experiment. Panel a) control with 0μM holoTf and no nanoshells added to the cells. The subsequent images show the amount of 100 nm Fe(III)-doped, silica nanoshells taken up by MDA-MB-231 cells when cells were pre-incubated for 2 hours with increasing amounts of holoTf: b) 0 μM holoTf; c) 20 μM holoTf; d) 200 μM holoTf; e) 500 μM holoTf; and f) 1000 μM holoTf. After the pre-incubation step, cells were incubated with 50 μg/mL of AlexaFluor 680 coated, 100nm Fe(III)-doped, silica nanoshells. All scale bars in the images are 25 microns.

Figure 5

Figure 5

Histograms obtained from FACS analysis of TfR blocking experiment. Panel a is a simplified version of the figure seen in panel b. The shift of the curve toward lower fluorescence intensity with added holo-Tf in panel a is the result of decreased nanoshell uptake by the MDA-MB-231 cells due to blocking of the TfR by holoTf. The histograms seen in panel b show that at least 500 μM holoTf needs to be added to the cells before a significant inhibition in nanoshell uptake could be observed.

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