A mechanically interlocked molecular system programmed for the delivery of an anticancer drug† †Electronic supplementary information (ESI): Experimental conditions and procedures, syntheses and compounds characterizations (1H, 13C and 2D NMR spectroscopic analyses and mass spectrometry data) as well as biological experiments. See DOI: 10.1039/c5sc00648a Click here for additional data file

• Published in: Chemical science (Cambridge) Vol. 6; no. 4; pp. 2608 - 2613
• Main Authors: Barat, Romain, Legigan, Thibaut, Tranoy-Opalinski, Isabelle, Renoux, Brigitte, Péraudeau, Elodie, Clarhaut, Jonathan, Poinot, Pauline, Fernandes, Antony E., Aucagne, Vincent, Leigh, David A., Papot, Sébastien
• Format: Journal Article
• Language: English
• Published: Royal Society of Chemistry 25.02.2015
• Subjects: Chemistry
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c5sc00648a

The development of mechanically interlocked molecular systems programmed to operate autonomously in biological environments is an emerging field of research with potential medicinal applications. The development of mechanically interlocked molecular systems programmed to operate autonomously in biological environments is an emerging field of research with potential medicinal applications. Within this framework, functional rotaxane- and pseudorotaxane-based architectures are starting to attract interest for the delivery of anticancer drugs, with the ultimate goal to improve the efficiency of cancer chemotherapy. Here, we report an enzyme-sensitive [2]-rotaxane designed to release a potent anticancer drug within tumor cells. The molecular device includes a protective ring that prevents the premature liberation of the drug in plasma. However, once located inside cancer cells the [2]-rotaxane leads to the release of the drug through the controlled disassembly of the mechanically interlocked components, in response to a determined sequence of two distinct enzymatic activations. Furthermore, in vitro biological evaluations reveal that this biocompatible functional system exhibits a noticeable level of selectivity for cancer cells overexpressing β-galactosidase.