title: 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 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.
  
  
  BACKGROUND
  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.
authors.affiliation: Department of Animal and Veterinary Science, University of Idaho, Moscow, ID 83844, USA.
authors.forename: Guankui
authors.initials: G
authors.lastname: Wang
authors.forename: Ann S
authors.initials: AS
authors.lastname: Norton
authors.forename: Deep
authors.initials: D
authors.lastname: Pokharel
authors.forename: Yuan
authors.initials: Y
authors.lastname: Song
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Hill
mesh_terms: D000818:Animals; D001692:Biological Transport; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis; D005453:Fluorescence; D006046:Gold / Q000737:chemistry*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D036103:Nanotechnology / Q000379:methods*; D009842:Oligopeptides / Q000378:metabolism*; D021382:Protein Sorting Signals; D018000:Receptors, Peptide; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: C064459:KDEL receptor; D009842:Oligopeptides; D021382:Protein Sorting Signals; D018000:Receptors, Peptide; D011993:Recombinant Fusion Proteins; C073762:lysyl-aspartyl-glutamyl-leucine; D049452:Green Fluorescent Proteins; D006046:Gold