Portal de Periódicos da CAPES

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

2017; Royal Society of Chemistry; Volume: 8; Issue: 5 Linguagem: Inglês

10.1039/c7sc00472a

2041-6539

Brigitte Renoux, Florian Raes, Thibaut Legigan, Elodie Péraudeau, Balkis Eddhif, Pauline Poinot, Isabelle Tranoy‐Opalinski, Jérôme Alsarraf, Oleksandr Koniev, Sergii Kolodych, Stéphanie Lerondel, Alain Le Pape, Jonathan Clarhaut, Sébastien Papot,

Glycosylation and Glycoproteins Research

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.