Elucidating mechanism cellular uptake removal protein
To date no class of targets is known that would allow direction of nanoparticle interactions with cells alternatively into one of these mutually exclusive events.
Using MCF-7 breast cancer cells expressing the human Y-receptor, we demonstrate that G protein-coupled receptors provide us with this option.
More selective interactions of nanoparticles with cells would substantially increase their potential for diagnostic and therapeutic applications.
Thus, it would not only be highly desirable that nanoparticles can be addressed to any cell with high target specificity and affinity, but that we could unequivocally define whether they rest immobilized on the cell surface as a diagnostic tag, or if they are internalized to serve as a delivery vehicle for drugs.
(2011) Impact of Gold Nanoparticle Concentration on their Cellular Uptake by MC3T3-E1 Mouse Osteoblastic Cells as Analyzed by Transmission Electron Microscopy. doi:10.4172/2157-7439.1000118 Copyright: © 2011 Mustafa T, et al.To whom correspondence should be addressed at Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of Colorado Anschutz Medical Campus, 12850 E.Montview Blvd, Mail Stop C238, Aurora, Colorado 80045.Ag NPs associated with each protein (HSA, BSA, and HDL) forming PCs as assessed by electron microscopy, hyperspectral analysis, ζ-potential, and hydrodynamic size.Addition of the PC decreased uptake of Ag NPs by rat lung epithelial and rat aortic endothelial cells.In vitro experiments typically measure the uptake of nanoparticles by exposing cells at the bottom of a culture plate to a suspension of nanoparticles, and it is generally assumed that this suspension is well-dispersed.However, nanoparticles can sediment, which means that the concentration of nanoparticles on the cell surface may be higher than the initial bulk concentration, and this could lead to increased uptake by cells.We found that agonist- and antagonist-modified nanoparticles bind to several receptor molecules at a time.This multiligand binding leads to five orders of magnitude increased-receptor affinities, compared with free ligand, in displacement studies.OVA PNPs enhance antigen uptake in a size-independent manner, and experience attenuated endosomal acidification as compared to soluble OVA. Expression of cytokines IL-1β and TNF-α were PNP size- and coating-dependent, with small (∼270 nm) nanoparticles triggering greater inflammatory cytokine production than large (∼560 nm) particles.IL-1β expression by DCs in response to PNP stimulation implies activation of the inflammasome, a pathway known to be activated by certain types of nanoparticulate adjuvants.