Tumor Targeting with an isoDGR–Drug Conjugate

Herein we report the first example of an isoDGR–drug conjugate (2), designed to release paclitaxel selectively within cancer cells expressing integrin α(V)β(3). Conjugate 2 was synthesized by connecting the isoDGR peptidomimetic 5 with paclitaxel via the lysosomally cleavable Val–Ala dipeptide linke...

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Autores principales: Zanella, Simone, Angerani, Simona, Pina, Arianna, López Rivas, Paula, Giannini, Clelia, Panzeri, Silvia, Arosio, Daniela, Caruso, Michele, Gasparri, Fabio, Fraietta, Ivan, Albanese, Clara, Marsiglio, Aurelio, Pignataro, Luca, Belvisi, Laura, Piarulli, Umberto, Gennari, Cesare
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Communications
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5488297/
https://www.ncbi.nlm.nih.gov/pubmed/28449309
http://dx.doi.org/10.1002/chem.201701844
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author Zanella, Simone
Angerani, Simona
Pina, Arianna
López Rivas, Paula
Giannini, Clelia
Panzeri, Silvia
Arosio, Daniela
Caruso, Michele
Gasparri, Fabio
Fraietta, Ivan
Albanese, Clara
Marsiglio, Aurelio
Pignataro, Luca
Belvisi, Laura
Piarulli, Umberto
Gennari, Cesare
author_facet Zanella, Simone
Angerani, Simona
Pina, Arianna
López Rivas, Paula
Giannini, Clelia
Panzeri, Silvia
Arosio, Daniela
Caruso, Michele
Gasparri, Fabio
Fraietta, Ivan
Albanese, Clara
Marsiglio, Aurelio
Pignataro, Luca
Belvisi, Laura
Piarulli, Umberto
Gennari, Cesare
author_sort Zanella, Simone
collection PubMed
description Herein we report the first example of an isoDGR–drug conjugate (2), designed to release paclitaxel selectively within cancer cells expressing integrin α(V)β(3). Conjugate 2 was synthesized by connecting the isoDGR peptidomimetic 5 with paclitaxel via the lysosomally cleavable Val–Ala dipeptide linker. Conjugate 2 displayed a low nanomolar affinity for the purified integrin α(V)β(3) receptor (IC(50)=11.0 nm). The tumor targeting ability of conjugate 2 was assessed in vitro in anti‐proliferative assays on two isogenic cancer cell lines characterized by different integrin α(V)β(3) expression: human glioblastoma U87 (α(V)β(3)+) and U87 β(3)‐KO (α(V)β(3)−). The isoDGR‐PTX conjugate 2 displayed a remarkable targeting index (TI=9.9), especially when compared to the strictly related RGD‐PTX conjugate 4 (TI=2.4).
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spelling pubmed-54882972017-07-24 Tumor Targeting with an isoDGR–Drug Conjugate Zanella, Simone Angerani, Simona Pina, Arianna López Rivas, Paula Giannini, Clelia Panzeri, Silvia Arosio, Daniela Caruso, Michele Gasparri, Fabio Fraietta, Ivan Albanese, Clara Marsiglio, Aurelio Pignataro, Luca Belvisi, Laura Piarulli, Umberto Gennari, Cesare Chemistry Communications Herein we report the first example of an isoDGR–drug conjugate (2), designed to release paclitaxel selectively within cancer cells expressing integrin α(V)β(3). Conjugate 2 was synthesized by connecting the isoDGR peptidomimetic 5 with paclitaxel via the lysosomally cleavable Val–Ala dipeptide linker. Conjugate 2 displayed a low nanomolar affinity for the purified integrin α(V)β(3) receptor (IC(50)=11.0 nm). The tumor targeting ability of conjugate 2 was assessed in vitro in anti‐proliferative assays on two isogenic cancer cell lines characterized by different integrin α(V)β(3) expression: human glioblastoma U87 (α(V)β(3)+) and U87 β(3)‐KO (α(V)β(3)−). The isoDGR‐PTX conjugate 2 displayed a remarkable targeting index (TI=9.9), especially when compared to the strictly related RGD‐PTX conjugate 4 (TI=2.4). John Wiley and Sons Inc. 2017-05-26 2017-06-12 /pmc/articles/PMC5488297/ /pubmed/28449309 http://dx.doi.org/10.1002/chem.201701844 Text en © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Communications
Zanella, Simone
Angerani, Simona
Pina, Arianna
López Rivas, Paula
Giannini, Clelia
Panzeri, Silvia
Arosio, Daniela
Caruso, Michele
Gasparri, Fabio
Fraietta, Ivan
Albanese, Clara
Marsiglio, Aurelio
Pignataro, Luca
Belvisi, Laura
Piarulli, Umberto
Gennari, Cesare
Tumor Targeting with an isoDGR–Drug Conjugate
title Tumor Targeting with an isoDGR–Drug Conjugate
title_full Tumor Targeting with an isoDGR–Drug Conjugate
title_fullStr Tumor Targeting with an isoDGR–Drug Conjugate
title_full_unstemmed Tumor Targeting with an isoDGR–Drug Conjugate
title_short Tumor Targeting with an isoDGR–Drug Conjugate
title_sort tumor targeting with an isodgr–drug conjugate
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5488297/
https://www.ncbi.nlm.nih.gov/pubmed/28449309
http://dx.doi.org/10.1002/chem.201701844
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