Barat, R., Legigan, T., Tranoy-Opalinski, I., Renoux, B., Peraudeau, E., Clarhaut, J., Poinot, P., Fernandes, A. E., Aucagne, V., Leigh, David A. and Papot, S.
Chemical Science (2015) 6 (4) 2608-2613 - doi : 10.1039/C5SC00648A
publié le , mis à jour le
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 -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 -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 [small beta]-galactosidase.