KDEL peptide gold nanoconstructs:

promising nanoplatforms for drug delivery

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

Research output: Contribution to journalArticle

18 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

Fingerprint

Drug delivery
Gold
Peptides
Endoplasmic Reticulum
Clathrin
Pharmaceutical Preparations
Degradation
Nanoparticles
lysyl-aspartyl-glutamyl-leucine
Clathrin-Coated Vesicles
Time and motion study
Golgi Apparatus
Sampling

Grant Number

  • ftok
  • oax

Cite this

Wang, GK ; Norton, AS ; Pokharel, Deep ; Song, Yuan ; Hill, RA. / KDEL peptide gold nanoconstructs: promising nanoplatforms for drug delivery. In: Nanomedicine: Nanotechnology, Biology, and Medicine. 2013 ; Vol. 9, No. 3. pp. 366-374.
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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.",
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KDEL peptide gold nanoconstructs: promising nanoplatforms for drug delivery. / Wang, GK; Norton, AS; Pokharel, Deep; Song, Yuan; Hill, RA.

In: Nanomedicine: Nanotechnology, Biology, and Medicine, Vol. 9, No. 3, 2013, p. 366-374.

Research output: Contribution to journalArticle

TY - JOUR

T1 - KDEL peptide gold nanoconstructs:

T2 - promising nanoplatforms for drug delivery

AU - Wang, GK

AU - Norton, AS

AU - Pokharel, Deep

AU - Song, Yuan

AU - Hill, RA

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AB - 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.

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