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KDEL Peptide Gold Nanostructures: A Promising Platform for Drug Delivery
Author(s) -
Wang Guankui,
Song Yuan,
Norton Ann,
Hill Rodney A.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb685
Subject(s) - colocalization , kdel , endocytosis , peptide , endoplasmic reticulum , internalization , microbiology and biotechnology , golgi apparatus , clathrin , endosome , chemistry , transfection , cell penetrating peptide , receptor mediated endocytosis , receptor , biology , biochemistry , gene
The objective was to elucidate the mechanisms of cellular uptake and trafficking of peptide gold nanostructures (Au‐Pep). Peptide A (PepA) contains the carboxy‐terminal sequence Lys‐Asp‐Glu‐Leu (KDEL). Peptide B (PepB) is a random sequence peptide with no known receptor‐binding activity. Au‐Pep were incubated with Sol8 cells for 15 mins in DMEM without serum, followed by a 1 h chase period in DMEM plus serum. Cellular compartments including clathrin‐coated vesicles, Golgi apparatus and endoplasmic reticulum (ER) were labeled for peptide colocalization studies. In a subsequent study, cells were transfected to overexpress KDEL receptor (KDELR), followed by Au‐Pep incubation. Cell imaging was performed using confocal fluorescence microscopy. The results showed that free PepA uptake was significantly greater in KDELR overexpressing cells, whereas there was no difference in PepB uptake, suggesting that free PepA was internalized via KDELR‐mediated endocytosis. However, Au‐Pep uptake was similar in KDELR overexpressing cells and controls, suggesting that KDELR‐mediated endocytosis was not predominant for Au‐Pep internalization. Colocalization data showed that for all peptide treatments, most localized in the ER. This may suggest that these peptides are trafficked via a retrograde coat protein complex I mediated transport pathway. In conclusion, Au‐PepA may provide a nanoplatform for drug delivery. This work was supported by the University of Idaho Blue Ribbon BANTech Initiative.