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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.