Gold nanoparticles (AuNPs) have been widely investigated as potential nanocarriers for drug delivery. In the present study, AuNPs were conjugated to a peptide that has a C-terminal Lys-Asp-Glu-Leu (KDEL) motif. In a pulse-chase study, time-course sampling revealed that AuNP-delivered KDEL peptides were rapidly localized to the endoplasmic reticulum (ER) in 5 to 15 min, and after 1h the majority of peptides were localized to the ER. Clathrin-coated vesicles and Golgi apparatus were also involved during the intracellular trafficking of KDEL peptide gold (AuNP-KDEL) nanoconstructs. Furthermore, overexpression of KDEL receptor (KDELR) significantly enhanced KDEL peptide uptake in both free and AuNP-conjugated forms. These data indicate that the AuNP-KDEL nanoconstructs are internalized via a clathrin-mediated pathway and trafficked to the ER via a retrograde transport pathway, bypassing the lysosomal degradation pathway. Thus, this novel approach to development of nanoconstruct-based drug delivery has the potential to evade intracellular degradation, enhancing drug efficacy.|From the Clinical Editor: In this study, gold nanoparticles were conjugated to a peptide with KDEL motif, resulting in internalization via a clathrin-mediated pathway and trafficking to the ER via retrograde transport meanwhile bypassing the lysosomal degradation pathway. This method results in a potential evasion of intracellular degradation, and enhanced drug efficacy. (C) 2013 Elsevier Inc. All rights reserved.
|Number of pages||9|
|Journal||Nanomedicine: Nanotechnology, Biology, and Medicine|
|Early online date||Oct 2012|
|Publication status||Published - 2013|
Wang, GK., Norton, AS., Pokharel, D., Song, Y., & Hill, RA. (2013). KDEL peptide gold nanoconstructs: promising nanoplatforms for drug delivery. Nanomedicine: Nanotechnology, Biology, and Medicine, 9(3), 366-374. https://doi.org/10.1016/j.nano.2012.09.002