A mechanically interlocked molecular system programmed for the delivery of an anticancer drugElectronic 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

• 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: 16.03.2015
• 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. 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. The development of mechanically interlocked molecular systems programmed to operate autonomously in biological environments is an emerging field of research with potential medicinal applications.