Abstract
There is a growing interest in isolating tumor cells from biological samples. Considering that circulating tumor cells can be rare in blood, it appears challenging to capture these cells onto a surface with high selectivity and sensitivity. In the present paper, we describe the design of functionalized surfaces aimed at selectively capturing tumor cells by using an RGD peptide ligand with either a tetrameric or a monomeric presentation. β-Cyclodextrin-coated self-assembled monolayers were used as platforms for the binding of RGD ligands endowed with a redox ferrocene cluster. The dissociation of the inclusion complex on the surface accounts for the release of the captured cells upon the electrochemical oxidation of ferrocene. For this purpose, we determined suitable RGD densities for both monovalent and tetravalent ligand presentations. The results indicate that the clustered RGD architecture efficiently improves selective cell capture at a very low RGD surface density (∼10 RGD per μm2) compared to the monovalent presentation (∼1000 RGD per μm2).
Highlights
IntroductionMultivalent interactions are ubiquitously observed in biological systems for a wide range of functions including integrinmediated cell adhesion to extracellular matrix (ECM). Among the integrin receptors, the αVβ3 integrin subclass has received special attention as it is involved in tumour progression such as aggressive metastatic cancer. Felding-Habermann et al have shown that this receptor contributes to circulating tumour cell (CTC) arrest. As cells expressing αVβ3 integrin interact with the ECM through the recognition of the ubiquitous triad sequenceRGD (Arg-Gly-Asp), a series of peptides containing the RGD sequence were developed for diagnosis and tumour therapy.4The cyclopentapeptide derivatives were found to bind the αVβ3 integrin. the multimeric presentation of RGD motifs appears to be a prerequisite for efficient integrin targeting. Our group and others have shown that multimeric compounds exhibit attractive biological properties. Recently, we have reported the benefit of tetrameric RGD derivatives for the near-infrared optical guided surgery of solid tumours and for tumour-targeted drug delivery
As the affinity of Fc for β-CD is low (Kd = 250 μM),13 the macromolecules require multivalent interaction to strengthen the binding of RGD bioconjugates on β-CD functionalized surfaces
We compared the effect of a multimeric RGD compound to its monomeric analogue on a specific αvβ3integrin expressing cell capture and release assay
Summary
Multivalent interactions are ubiquitously observed in biological systems for a wide range of functions including integrinmediated cell adhesion to extracellular matrix (ECM). Among the integrin receptors, the αVβ3 integrin subclass has received special attention as it is involved in tumour progression such as aggressive metastatic cancer. Felding-Habermann et al have shown that this receptor contributes to circulating tumour cell (CTC) arrest. As cells expressing αVβ3 integrin interact with the ECM through the recognition of the ubiquitous triad sequenceRGD (Arg-Gly-Asp), a series of peptides containing the RGD sequence were developed for diagnosis and tumour therapy.4The cyclopentapeptide derivatives were found to bind the αVβ3 integrin. the multimeric presentation of RGD motifs appears to be a prerequisite for efficient integrin targeting. Our group and others have shown that multimeric compounds exhibit attractive biological properties. Recently, we have reported the benefit of tetrameric RGD derivatives for the near-infrared optical guided surgery of solid tumours and for tumour-targeted drug delivery.. Multivalent interactions are ubiquitously observed in biological systems for a wide range of functions including integrinmediated cell adhesion to extracellular matrix (ECM).. The αVβ3 integrin subclass has received special attention as it is involved in tumour progression such as aggressive metastatic cancer.. Felding-Habermann et al have shown that this receptor contributes to circulating tumour cell (CTC) arrest.. As cells expressing αVβ3 integrin interact with the ECM through the recognition of the ubiquitous triad sequence. The cyclopentapeptide derivatives were found to bind the αVβ3 integrin.. The multimeric presentation of RGD motifs appears to be a prerequisite for efficient integrin targeting.. We have reported the benefit of tetrameric RGD derivatives for the near-infrared optical guided surgery of solid tumours and for tumour-targeted drug delivery.
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