Elucidating the mechanism of cellular uptake and removal of protein dating scoundrels

Posted by / 26-Nov-2020 16:20

Elucidating the mechanism of cellular uptake and removal of protein

Specific binding and uptake of agonist-modified QDs.

Confocal fluorescence micrographs and corresponding brightfield images of cell clusters after incubation with [Lys4(αN-Acetyl-Cys), Arg6, Pro34]-p NPY-QDs (10 n M).

More than 800 G protein-coupled receptors in humans provide us with the paramount advantage that targeting of a plethora of cells is possible, and that switching from cell recognition to cell uptake is simply a matter of nanoparticle surface modification with the appropriate choice of ligand type. To investigate the validity of both hypotheses, we selected the human neuropeptide Y (NPY) Y-receptor as a model receptor.

To date, no mechanism is known that would allow us to design particles destined for a single target structure such that they can be addressed exclusively to the cell surface or alternatively to the cell interior.

Using MCF-7 breast cancer cells expressing the human Y(1)-receptor, we demonstrate that G protein-coupled receptors provide us with this option. The family of G protein-coupled receptors (GPCRs), which exhibit high tissue specificity and represent the largest class of receptors in the human genome (11), appeared to be a promising choice.

The nanoparticles are delivered into living MCF-7 cells in vesicular structures.

Except for the cell nuclei, the particles are located throughout the cell bodies.

Both agonist- and antagonist-modified QDs exhibited specific cell binding, but there was a tremendous difference with respect to cellular uptake. The cells formed vesicular structures containing agonist-modified QDs, which indicate that the nanoparticles had been transported into the cells (-stack images.

To further elucidate the location of agonist-modified particles after their interaction with cells, images representing optical sections through the cells were taken from MCF-7 cells after incubation with [Lys, strong fluorescence because of the QDs can be found throughout the cells, except for the cell nuclei.

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Using MCF-7 breast cancer cells expressing the human Y-receptor, we demonstrate that G protein-coupled receptors provide us with this option.