KDEL peptide gold nanoconstructs: promising nanoplatforms for drug delivery

Abstract 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 p...

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Bibliographic Details
Published in:Nanomedicine 2013-04, Vol.9 (3), p.366-374
Main Authors: Wang, Guankui, PhD, Norton, Ann S., MS, Pokharel, Deep, BS, Song, Yuan, MS, Hill, Rodney A., PhD
Format: Article
Language:English
Subjects:
Animals
Biological Transport
Drug Delivery Systems - methods
Endocytosis
Fluorescence
Gold - chemistry
Gold nanoparticles
Green Fluorescent Proteins - metabolism
Internal Medicine
Intracellular Space - metabolism
KDEL receptor
Metal Nanoparticles - chemistry
Mice
Nanotechnology - methods
Oligopeptides - metabolism
Peptide
Protein Sorting Signals
Receptors, Peptide
Recombinant Fusion Proteins - metabolism
Trafficking
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Summary:Abstract 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 1 h 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.
ISSN:1549-9634
1549-9642
DOI:10.1016/j.nano.2012.09.002