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

被引：133

作者：

Nakase, Ikuhiko ^{[1
]}

Konishi, Yusuke ^{[1
]}

Ueda, Masashi ^{[2
,3
]}

Saji, Hideo ^{[3
]}

Futaki, Shiroh ^{[1
]}

机构：

[1] Kyoto Univ, Inst Chem Res, Kyoto 6110011, Japan

[2] Kyoto Univ, Kyoto Univ Hosp, Radioisotopes Res Lab, Fac Med, Kyoto 6068507, Japan

[3] Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Pathofunct Bioanal, Kyoto 6068501, Japan

来源：

JOURNAL OF CONTROLLED RELEASE | 2012年 / 159卷 / 02期

关键词：

Arginine-rich cell-penetrating peptide; In vivo fluorescent imaging; Biodistribution; Tumor accumulation; Doxorubicin; Drug delivery; MEMBRANE-ASSOCIATED PROTEOGLYCANS; HUMAN BREAST-CANCER; MACROMOLECULAR THERAPEUTICS; TARGETED DELIVERY; IMPROVES SURVIVAL; PLASMA-MEMBRANE; FAB FRAGMENT; ADRIAMYCIN; MACROPINOCYTOSIS; PROTEINS;

D O I：

10.1016/j.jconrel.2012.01.016

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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. (C) 2012 Elsevier B.V. All rights reserved.

引用

页码：181 / 188

页数：8

共 51 条

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