Abstract
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.
Copyright © 2012 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / administration & dosage*
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Antineoplastic Agents / pharmacokinetics
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Antineoplastic Agents / therapeutic use
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CHO Cells
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Carrier Proteins / chemistry
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Cell-Penetrating Peptides / chemistry
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Cell-Penetrating Peptides / pharmacokinetics*
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Cricetinae
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Doxorubicin / administration & dosage*
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Doxorubicin / pharmacokinetics
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Doxorubicin / therapeutic use
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Drug Carriers / chemistry
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Drug Carriers / pharmacokinetics*
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Female
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HeLa Cells
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Humans
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Microscopy, Confocal
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Oligopeptides / chemistry*
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Peptide Fragments / chemistry
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Stereoisomerism
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Time Factors
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Tissue Distribution
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Xenograft Model Antitumor Assays
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tat Gene Products, Human Immunodeficiency Virus / chemistry
Substances
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Antineoplastic Agents
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Carrier Proteins
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Cell-Penetrating Peptides
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Drug Carriers
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Oligopeptides
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Peptide Fragments
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octa-arginine peptide
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tat Gene Products, Human Immunodeficiency Virus
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tat peptide (48-60), Human immunodeficiency virus 1
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Doxorubicin
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penetratin