Nuclear localization of cell-penetrating peptides

UnrestrictedNuclear transport of cell-penetrating peptides is commonly believed to be facilitated by transduction. In this report, nuclear localization of a range of peptides were examined, including three highly endocytosed peptides, MAP, K9 and R16, and two peptides internalized primarily by transduction, Tat and R9. Results show that nuclear localization of MAP and R16 is significantly larger than both transduction peptides and K9. Total internalization follows the same pattern, suggesting that sheer volume facilitates high nuclear localization. Thus, there appears to be a correlation between endocytosis efficiency and nuclear localization of cell-penetrating peptides, if the peptide is resistant to degradation in the endocytic pathway. Inhibition of endosomal acidification causes fluctuations in nuclear localization of endocytosed peptides, suggesting that these peptides are able to escape endosomes and be transported to the nucleus. These data indicate that some highly endocytosed peptides may be more suitable for nuclear drug delivery than previously thought