In Vivo Noninvasive Optical Imaging of Receptor-Mediated RGD Internalization Using Self-Quenched Cy5-Labeled RAFT-c(-RGDfK-)
We reported that regioselectively addressable functionalized template (RAFT)-c(-RGDfK-) 4 presenting four cyclic (Arg-Gly-Asp) (cRGD) peptides targets integrin a V b 3 with an improved specificity compared with monomeric cRGD. In this study, we improved this vector by creating a “stealth” molecule i...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publications
2007-01-01
|
| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.2310/7290.2007.00002 |
| _version_ | 1797288647838400512 |
|---|---|
| author | Zhao-Hui Jin Jesus Razkin Veronique Josserand Didier Boturyn Alexeï Grichine Isabelle Texier Marie-Christine Favrot Pascal Dumy Jean-Luc Coll |
| author_facet | Zhao-Hui Jin Jesus Razkin Veronique Josserand Didier Boturyn Alexeï Grichine Isabelle Texier Marie-Christine Favrot Pascal Dumy Jean-Luc Coll |
| author_sort | Zhao-Hui Jin |
| collection | DOAJ |
| description | We reported that regioselectively addressable functionalized template (RAFT)-c(-RGDfK-) 4 presenting four cyclic (Arg-Gly-Asp) (cRGD) peptides targets integrin a V b 3 with an improved specificity compared with monomeric cRGD. In this study, we improved this vector by creating a “stealth” molecule in which a fluorescence quencher (Q) is linked to Cy5 via a disulfide bond (-SS-). RAFT-c(-RGDfK-) 4 -Cy5-SS-Q fluorescence is quenched unless activated by reduction during internalization. RAFT-c(-RGDfK-) 4 -Cy5-SS-Q fluorescence was negligible when compared with the control but totally recovered after cleavage of the disulfide bridge. Confocal microscopy showed that only the intracellular Cy5 signal could be detected using RAFT-c(-RGDfK-) 4 -Cy5-SS-Q, confirming that uncleaved extracellular molecules are not visible. Whole-body imaging of mice bearing subcutaneous tumors injected intravenously with RAFT-c(-RGDfK-) 4 -Cy5-SS-Q showed a very significant enhancement of the fluorescent contrast in tumors compared with the unquenched molecule. Histology of the tumor confirmed the intracellular accumulation of Cy5. These results demonstrate that the presence of a labile disulfide bridge between the targeting vector and a drug mimetic is an efficient way to deliver a dye, or a drug, intracellularly. In addition, this quenched RAFT-c(-RGDfK-) 4 -Cy5-SS-Q probe is a very powerful vector for imaging tumor masses and investigating in vivo RGD-mediated internalization. |
| first_indexed | 2024-03-07T18:52:31Z |
| format | Article |
| id | doaj.art-8fa4743c8b9541aa96bfca0dd0c2783d |
| institution | Directory Open Access Journal |
| issn | 1536-0121 |
| language | English |
| last_indexed | 2024-03-07T18:52:31Z |
| publishDate | 2007-01-01 |
| publisher | SAGE Publications |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj.art-8fa4743c8b9541aa96bfca0dd0c2783d2024-03-02T01:14:54ZengSAGE PublicationsMolecular Imaging1536-01212007-01-01610.2310/7290.2007.0000210.2310_7290.2007.00002In Vivo Noninvasive Optical Imaging of Receptor-Mediated RGD Internalization Using Self-Quenched Cy5-Labeled RAFT-c(-RGDfK-)Zhao-Hui JinJesus RazkinVeronique JosserandDidier BoturynAlexeï GrichineIsabelle TexierMarie-Christine FavrotPascal DumyJean-Luc CollWe reported that regioselectively addressable functionalized template (RAFT)-c(-RGDfK-) 4 presenting four cyclic (Arg-Gly-Asp) (cRGD) peptides targets integrin a V b 3 with an improved specificity compared with monomeric cRGD. In this study, we improved this vector by creating a “stealth” molecule in which a fluorescence quencher (Q) is linked to Cy5 via a disulfide bond (-SS-). RAFT-c(-RGDfK-) 4 -Cy5-SS-Q fluorescence is quenched unless activated by reduction during internalization. RAFT-c(-RGDfK-) 4 -Cy5-SS-Q fluorescence was negligible when compared with the control but totally recovered after cleavage of the disulfide bridge. Confocal microscopy showed that only the intracellular Cy5 signal could be detected using RAFT-c(-RGDfK-) 4 -Cy5-SS-Q, confirming that uncleaved extracellular molecules are not visible. Whole-body imaging of mice bearing subcutaneous tumors injected intravenously with RAFT-c(-RGDfK-) 4 -Cy5-SS-Q showed a very significant enhancement of the fluorescent contrast in tumors compared with the unquenched molecule. Histology of the tumor confirmed the intracellular accumulation of Cy5. These results demonstrate that the presence of a labile disulfide bridge between the targeting vector and a drug mimetic is an efficient way to deliver a dye, or a drug, intracellularly. In addition, this quenched RAFT-c(-RGDfK-) 4 -Cy5-SS-Q probe is a very powerful vector for imaging tumor masses and investigating in vivo RGD-mediated internalization.https://doi.org/10.2310/7290.2007.00002 |
| spellingShingle | Zhao-Hui Jin Jesus Razkin Veronique Josserand Didier Boturyn Alexeï Grichine Isabelle Texier Marie-Christine Favrot Pascal Dumy Jean-Luc Coll In Vivo Noninvasive Optical Imaging of Receptor-Mediated RGD Internalization Using Self-Quenched Cy5-Labeled RAFT-c(-RGDfK-) Molecular Imaging |
| title | In Vivo Noninvasive Optical Imaging of Receptor-Mediated RGD Internalization Using Self-Quenched Cy5-Labeled RAFT-c(-RGDfK-) |
| title_full | In Vivo Noninvasive Optical Imaging of Receptor-Mediated RGD Internalization Using Self-Quenched Cy5-Labeled RAFT-c(-RGDfK-) |
| title_fullStr | In Vivo Noninvasive Optical Imaging of Receptor-Mediated RGD Internalization Using Self-Quenched Cy5-Labeled RAFT-c(-RGDfK-) |
| title_full_unstemmed | In Vivo Noninvasive Optical Imaging of Receptor-Mediated RGD Internalization Using Self-Quenched Cy5-Labeled RAFT-c(-RGDfK-) |
| title_short | In Vivo Noninvasive Optical Imaging of Receptor-Mediated RGD Internalization Using Self-Quenched Cy5-Labeled RAFT-c(-RGDfK-) |
| title_sort | in vivo noninvasive optical imaging of receptor mediated rgd internalization using self quenched cy5 labeled raft c rgdfk |
| url | https://doi.org/10.2310/7290.2007.00002 |
| work_keys_str_mv | AT zhaohuijin invivononinvasiveopticalimagingofreceptormediatedrgdinternalizationusingselfquenchedcy5labeledraftcrgdfk AT jesusrazkin invivononinvasiveopticalimagingofreceptormediatedrgdinternalizationusingselfquenchedcy5labeledraftcrgdfk AT veroniquejosserand invivononinvasiveopticalimagingofreceptormediatedrgdinternalizationusingselfquenchedcy5labeledraftcrgdfk AT didierboturyn invivononinvasiveopticalimagingofreceptormediatedrgdinternalizationusingselfquenchedcy5labeledraftcrgdfk AT alexeigrichine invivononinvasiveopticalimagingofreceptormediatedrgdinternalizationusingselfquenchedcy5labeledraftcrgdfk AT isabelletexier invivononinvasiveopticalimagingofreceptormediatedrgdinternalizationusingselfquenchedcy5labeledraftcrgdfk AT mariechristinefavrot invivononinvasiveopticalimagingofreceptormediatedrgdinternalizationusingselfquenchedcy5labeledraftcrgdfk AT pascaldumy invivononinvasiveopticalimagingofreceptormediatedrgdinternalizationusingselfquenchedcy5labeledraftcrgdfk AT jeanluccoll invivononinvasiveopticalimagingofreceptormediatedrgdinternalizationusingselfquenchedcy5labeledraftcrgdfk |