Membrane-permeable
peptide carriers are attractive
drug delivery tools. Among such carriers, the
protein transduction domain (PTD) of the human immunodeficiency virus-type 1
Tat protein is most frequently used and has been successfully shown to deliver a large variety of cargoes. The Tat PTD can facilitate the uptake of large, biologically active molecules into mammalian cells, and recent studies have shown that it can mediate the delivery of different cargoes into tissues throughout a living organism. Given that the Tat PTD-mediated delivery is size-independent, this technology could make previously non-applicable large molecules usable to modulate
biological function in vivo and treat human diseases. It is likely that the
peptide carrier-mediated intracellular delivery process encompasses multiple mechanisms, but endocytic pathways are the predominant internalization routes. Tat PTD has been successfully used in preclinical models for the study of
cancer,
ischemia,
inflammation,
analgesia, and anesthesia. Our recent studies have shown that intraperitoneally injected fusion Tat
peptide Tat-PSD-95 PDZ2 can be delivered into the spinal cord to dose-dependently disrupt
protein-
protein interactions between PSD-95 and
NMDA receptors. This
peptide significantly inhibits chronic inflammatory
pain and reduces the threshold for
halothane anesthesia. The ability of the Tat PTD to target any cell is advantageous in some respects. However, the drug delivery system will be more attractive if we can modify the Tat PTD to deliver cargo only into desired organs to avoid possible side effects.