Research Article Enhanced heparan sulfate proteoglycan-mediated uptake of cell-penetrating peptide-modified liposomes

Protein transduction domains (PTDs) are used to enhance cellular uptake of drugs, proteins, polynu- cleotides or liposomes. In this study, functionalized An- tennapedia (Antp, aa 43-58) and HIV Tat (aa 47-57) peptides were coupled to small unilamellar liposomes via thiol-maleimide linkage. Modified liposomes showed higher uptake into a panel of cell lines including tumor and dendritic cells than unmodified control liposomes. Liposome uptake was time and concentration dependent as analyzed by flow cytometry and live-cell microscopy. At least 100 PTD molecules per small unilamellar lipo- some (100 ± 30 nm) were necessary for efficient translo- cation into cells. Cellular uptake of PTD-modified lipo- somes was 15- to 25-fold increased compared to unmod-