In vivo optical imaging of integrin αV-β3 in mice using multivalent or monovalent cRGD targeting vectors

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Abstract

Background

The cRGD peptide is a promising probe for early non-invasive detection of tumors. This study aimed to demonstrate how RAFT-c(-RGDfK-) ₄, a molecule allowing a tetrameric presentation of cRGD, improved cRGD-targeting potential using in vivo models of α _Vβ ₃-positive or negative tumors.

Results

We chose the human embryonic kidney cells HEK293(β ₃) (high levels of α _Vβ ₃) or HEK293(β ₁) (α _Vβ ₃-negative but expressing α _Vand β1) engrafted subcutaneously (s.c.) in mice. Non-invasive in vivo optical imaging demonstrated that as compared to its monomeric cRGD analogue, Cy5-RAFT-c(-RGDfK-) ₄injected intravenously had higher uptake, prolonged retention and markedly enhanced contrast in HEK293(β ₃) than in the HEK293(β ₁) tumors. Blocking studies further demonstrated the targeting specificity and competitive binding ability of the tetramer.

Conclusion

In conclusion, we demonstrated that Cy5-RAFT-c(-RGDfK-) ₄was indeed binding to the α _Vβ ₃receptor and with an improved activity as compared to its monomeric analog, confirming the interest of using multivalent ligands. Intravenous injection of Cy5-RAFT-c(-RGDfK-) ₄in this novel pair of HEK293(β ₃) and HEK293(β ₁) tumors, provided tumor/skin ratio above 15. Such an important contrast plus the opportunity to use the HEK293(β ₁) negative control cell line are major assets for the community of researchers working on the design and amelioration of RGD-targeted vectors or on RGD-antagonists.

Related collections

Most cited references 27

Record: found
Abstract: found
Article: not found

RGD and other recognition sequences for integrins.

E Ruoslahti (1996)

Proteins that contain the Arg-Gly-Asp (RGD) attachment site, together with the integrins that serve as receptors for them, constitute a major recognition system for cell adhesion. The RGD sequence is the cell attachment site of a large number of adhesive extracellular matrix, blood, and cell surface proteins, and nearly half of the over 20 known integrins recognize this sequence in their adhesion protein ligands. Some other integrins bind to related sequences in their ligands. The integrin-binding activity of adhesion proteins can be reproduced by short synthetic peptides containing the RGD sequence. Such peptides promote cell adhesion when insolubilized onto a surface, and inhibit it when presented to cells in solution. Reagents that bind selectively to only one or a few of the RGD-directed integrins can be designed by cyclizing peptides with selected sequences around the RGD and by synthesizing RGD mimics. As the integrin-mediated cell attachment influences and regulates cell migration, growth, differentiation, and apoptosis, the RGD peptides and mimics can be used to probe integrin functions in various biological systems. Drug design based on the RGD structure may provide new treatments for diseases such as thrombosis, osteoporosis, and cancer.

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Record: found
Abstract: not found
Article: not found

Integrins: a family of cell surface receptors.

R O Hynes (1987)

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Record: found
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Cell-specific targeting of nanoparticles by multivalent attachment of small molecules.

Ralph Weissleder, Kimberly Kelly, Eric Yi Sun … (2005)

Nanomaterials with precise biological functions have considerable potential for use in biomedical applications. Here we investigate whether multivalent attachment of small molecules can increase specific binding affinity and reveal new biological properties of such nanomaterials. We describe the parallel synthesis of a library comprising 146 nanoparticles decorated with different synthetic small molecules. Using fluorescent magnetic nanoparticles, we rapidly screened the library against different cell lines and discovered a series of nanoparticles with high specificity for endothelial cells, activated human macrophages or pancreatic cancer cells. Hits from the last-mentioned screen were shown to target pancreatic cancer in vivo. The method and described materials could facilitate development of functional nanomaterials for applications such as differentiating cell lines, detecting distinct cellular states and targeting specific cell types.

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Author and article information

Journal

Journal ID (nlm-ta): Mol Cancer

Title: Molecular Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 1476-4598

Publication date Collection: 2007

Publication date (Electronic): 12 June 2007

Volume: 6

Page: 41

Affiliations

[1 ]INSERM, U823, Cibles Diagnostiques ou Thérapeutiques et Vectorisation des Drogues dans le Cancer du Poumon, Institut Albert Bonniot, 38706 La Tronche Cedex, France

[2 ]Université Joseph Fourier, 38041 Grenoble Cedex 9, France

[3 ]CNRS, UMR5616, Ingénierie Moléculaire et Chimie des Composés Bio-organiques, LEDSS, 38041 Grenoble Cedex 9, France

Article

Publisher ID: 1476-4598-6-41

DOI: 10.1186/1476-4598-6-41

PMC ID: 1906830

PubMed ID: 17565663

SO-VID: 6fc6f0ba-79d6-4a64-a036-e3c2a39c25b4

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.