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

Ikuhiko Nakase, Yusuke Konishi, Masashi Ueda, Hideo Saji, Shiroh Futaki

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96 Citations (Scopus)


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 (4 mg doxorubicin/kg) effectively suppressed tumor proliferation, with no significant decrease in mouse weight, whereas administration of doxorubicin itself (6 mg/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.

Original languageEnglish
Pages (from-to)181-188
Number of pages8
JournalJournal of Controlled Release
Issue number2
Publication statusPublished - Apr 30 2012
Externally publishedYes



  • Arginine-rich cell-penetrating peptide
  • Biodistribution
  • Doxorubicin
  • Drug delivery
  • In vivo fluorescent imaging
  • Tumor accumulation

ASJC Scopus subject areas

  • Pharmaceutical Science

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