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Targeting the tumour microenvironment with an enzyme-responsive drug delivery system for the efficient therapy of breast and pancreatic cancers

The development of novel therapeutic strategies allowing the destruction of tumour cells while sparing healthy tissues is one of the main challenges of cancer chemotherapy. Here, we report on the design and antitumour activity of a low-molecular-weight drug delivery system programmed for the selecti...

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Autores principales: Renoux, Brigitte, Raes, Florian, Legigan, Thibaut, Péraudeau, Elodie, Eddhif, Balkis, Poinot, Pauline, Tranoy-Opalinski, Isabelle, Alsarraf, Jérôme, Koniev, Oleksandr, Kolodych, Sergii, Lerondel, Stéphanie, Le Pape, Alain, Clarhaut, Jonathan, Papot, Sébastien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5417048/
https://www.ncbi.nlm.nih.gov/pubmed/28507714
http://dx.doi.org/10.1039/c7sc00472a
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author Renoux, Brigitte
Raes, Florian
Legigan, Thibaut
Péraudeau, Elodie
Eddhif, Balkis
Poinot, Pauline
Tranoy-Opalinski, Isabelle
Alsarraf, Jérôme
Koniev, Oleksandr
Kolodych, Sergii
Lerondel, Stéphanie
Le Pape, Alain
Clarhaut, Jonathan
Papot, Sébastien
author_facet Renoux, Brigitte
Raes, Florian
Legigan, Thibaut
Péraudeau, Elodie
Eddhif, Balkis
Poinot, Pauline
Tranoy-Opalinski, Isabelle
Alsarraf, Jérôme
Koniev, Oleksandr
Kolodych, Sergii
Lerondel, Stéphanie
Le Pape, Alain
Clarhaut, Jonathan
Papot, Sébastien
author_sort Renoux, Brigitte
collection PubMed
description The development of novel therapeutic strategies allowing the destruction of tumour cells while sparing healthy tissues is one of the main challenges of cancer chemotherapy. Here, we report on the design and antitumour activity of a low-molecular-weight drug delivery system programmed for the selective release of the potent monomethylauristatin E in the tumour microenvironment of solid tumours. After intravenous administration, this compound binds covalently to plasmatic albumin through Michael addition, thereby enabling its passive accumulation in tumours where extracellular β-glucuronidase initiates the selective release of the drug. This targeting device produces outstanding therapeutic efficacy on orthotopic triple-negative mammary and pancreatic tumours in mice (50% and 33% of mice with the respective tumours cured), leading to impressive reduction or even disappearance of tumours without inducing side effects.
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spelling pubmed-54170482017-05-15 Targeting the tumour microenvironment with an enzyme-responsive drug delivery system for the efficient therapy of breast and pancreatic cancers Renoux, Brigitte Raes, Florian Legigan, Thibaut Péraudeau, Elodie Eddhif, Balkis Poinot, Pauline Tranoy-Opalinski, Isabelle Alsarraf, Jérôme Koniev, Oleksandr Kolodych, Sergii Lerondel, Stéphanie Le Pape, Alain Clarhaut, Jonathan Papot, Sébastien Chem Sci Chemistry The development of novel therapeutic strategies allowing the destruction of tumour cells while sparing healthy tissues is one of the main challenges of cancer chemotherapy. Here, we report on the design and antitumour activity of a low-molecular-weight drug delivery system programmed for the selective release of the potent monomethylauristatin E in the tumour microenvironment of solid tumours. After intravenous administration, this compound binds covalently to plasmatic albumin through Michael addition, thereby enabling its passive accumulation in tumours where extracellular β-glucuronidase initiates the selective release of the drug. This targeting device produces outstanding therapeutic efficacy on orthotopic triple-negative mammary and pancreatic tumours in mice (50% and 33% of mice with the respective tumours cured), leading to impressive reduction or even disappearance of tumours without inducing side effects. Royal Society of Chemistry 2017-05-01 2017-03-08 /pmc/articles/PMC5417048/ /pubmed/28507714 http://dx.doi.org/10.1039/c7sc00472a Text en This journal is © The Royal Society of Chemistry 2017 http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Chemistry
Renoux, Brigitte
Raes, Florian
Legigan, Thibaut
Péraudeau, Elodie
Eddhif, Balkis
Poinot, Pauline
Tranoy-Opalinski, Isabelle
Alsarraf, Jérôme
Koniev, Oleksandr
Kolodych, Sergii
Lerondel, Stéphanie
Le Pape, Alain
Clarhaut, Jonathan
Papot, Sébastien
Targeting the tumour microenvironment with an enzyme-responsive drug delivery system for the efficient therapy of breast and pancreatic cancers
title Targeting the tumour microenvironment with an enzyme-responsive drug delivery system for the efficient therapy of breast and pancreatic cancers
title_full Targeting the tumour microenvironment with an enzyme-responsive drug delivery system for the efficient therapy of breast and pancreatic cancers
title_fullStr Targeting the tumour microenvironment with an enzyme-responsive drug delivery system for the efficient therapy of breast and pancreatic cancers
title_full_unstemmed Targeting the tumour microenvironment with an enzyme-responsive drug delivery system for the efficient therapy of breast and pancreatic cancers
title_short Targeting the tumour microenvironment with an enzyme-responsive drug delivery system for the efficient therapy of breast and pancreatic cancers
title_sort targeting the tumour microenvironment with an enzyme-responsive drug delivery system for the efficient therapy of breast and pancreatic cancers
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5417048/
https://www.ncbi.nlm.nih.gov/pubmed/28507714
http://dx.doi.org/10.1039/c7sc00472a
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