KDEL peptide gold nanoconstructs: promising nanoplatforms for drug delivery

GK Wang, AS Norton, Deep Pokharel, Yuan Song, RA Hill

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

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 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.
Original languageEnglish
Pages (from-to)366-374
Number of pages9
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume9
Issue number3
Early online dateOct 2012
DOIs
Publication statusPublished - 2013

Grant Number

  • ftok
  • oax

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