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The use of RGDGWK-lipopeptide to selectively deliver genes to mouse tumor vasculature and its complexation with p53 to inhibit tumor growth

Paper ID Volume ID Publish Year Pages File Format Full-Text
9366 627 2010 11 PDF Available
Title
The use of RGDGWK-lipopeptide to selectively deliver genes to mouse tumor vasculature and its complexation with p53 to inhibit tumor growth
Abstract

In vivo selection of phage display libraries have been exploited successfully in the past to isolate various high affinity conformationally strained cyclic peptide ligands (CX5–7C, peptides flanked by a cysteine residue on each side) for integrin receptors capable of selectively homing to tumor vasculatures. Previously, such phase display library studies have shown that integrin α5β1 binds with high affinity to cyclic peptides containing CRGDGWC motif. Herein we show that a lipopeptide with just the RGDGW motif (without the flanking cysteine groups) covalently attached to the lysine residue of a monolysinylated cationic amphiphile (RGDGWK-lipopeptide 1) delivers genes to cultured cells preferably via α5β1 integrins. Importantly, remarkable tumor growth inhibition was observed when the electrostatic complex of the RGDGWK-lipopeptide 1 and the anti-cancer p53 gene was intravenously administered in C57BL/6 J mice bearing the aggressive B16F10 tumor. Immunohistochemical staining of mice tumor cryosections with vasculature markers combined with monitoring expression of the green fluorescence protein in the same tumor cryosections revealed that the RGDGWK-lipopeptide 1 targets genes to tumor vasculatures. The colocalization of the TUNEL (terminal deoxyuridine triphosphate nick-end labeling, a widely used marker of apoptosis) and VE-cadherin (markers of tumor endothelial cells) positive cells in tumor cryosections support the notion that the remarkable tumor growth inhibition property of the RGDGWK-lipopeptide 1:p53 complex is initiated through apoptosis of the tumor endothelial cells.

Keywords
Tumor vasculature targeting; Integrin targeting; Tumor growth inhibitionEDCI, 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride; HOBt, 1-Hydroxybenztriazole; BOC, Tert-butyloxy carbonyl; Cbz, Benzyloxycarbonyl; Chol, Cholesterol; DCM, Dichlorome
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The use of RGDGWK-lipopeptide to selectively deliver genes to mouse tumor vasculature and its complexation with p53 to inhibit tumor growth
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 7, March 2010, Pages 1787–1797
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us