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Accumulation of arginine-rich cell-penetrating peptides in tumors and the potential for anticancer drug delivery in vivo

Nakase, Ikuhiko, Konishi, Yusuke, Ueda, Masashi, Saji, Hideo, Futaki, Shiroh
Journal of controlled release 2012 v.159 no.2 pp. 181-188
Human immunodeficiency virus 1, doxorubicin, glycosaminoglycans, image analysis, intravenous injection, mice, neoplasms, peptides, weight loss
We investigated the biodistribution of arginine-rich cell-penetrating peptides (CPPs) in tumor-xenografted nude mice after intravenous injection of fluorescently labeled CPPs using in vivo imaging. The CPPs used included HIV-1 Tat (48–60), penetratin, and the l- and d-enantiomers of oligoarginines (8, 12, and 16 residues), all of which are reported to have high cell penetration. Among the tested peptides, high accumulation in tumors was observed for the D-form of octaarginine (r8), and glycosaminoglycans played a key role. Injection of an r8-doxorubicin conjugate (4mg doxorubicin/kg) effectively suppressed tumor proliferation, with no significant decrease in mouse weight, whereas administration of doxorubicin itself (6mg/kg), yielding a similar degree of tumor-growth suppression, resulted in significant weight loss. These results suggest the potential of r8 as a prototypic tumor-targeting vector.