KDEL peptide gold nanoconstructs: promising nanoplatforms for drug delivery

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 EditorIn 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.

Graphical AbstractNanoconstructs may be internalized via several known endocytosis pathways including macropinocytosis, clathrin-mediated, caveolae-mediated pathway or non-specific pathway such as membrane adsorption. Once the nanoconstructs enter the cells, they will be transported through different subcellular compartments. Our studies showed that a clathrin-mediated pathway is predominant during the internalization of Lys–Asp–Glu–Leu (KDEL) peptide gold nanoconstructs and these nanoconstructs are transported to the endoplasmic reticulum via a retrograde pathway mediated by coat protein I (COPI). Overall, the KDEL peptide gold nanoconstructs have potential as a nanoplatform for high efficacy drug delivery.Figure optionsDownload high-quality image (112 K)Download as PowerPoint slide