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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.

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

Chemical Science (2015) 6 (4) 2608-2613 - doi : 10.1039/C5SC00648A

par Frapart - publié le , mis à jour le

Abstract :

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 [small beta]-galactosidase.