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

Romain Barat (1) , Thibaut Legigan (1) , I. Tranoy-Opalinski (1) , Brigitte Renoux (1) , Elodie Peraudeau (2, 3) , Jonathan Clarhaut (1, 3) , Pauline Poinot (1) , Anthony E. Fernandes (4) , Vincent Aucagne (5) , David Leigh (6) , Sébastien Papot (1)

1 IC2MP [Poitiers] - Institut de chimie des milieux et matériaux de Poitiers [UMR 7285]
2 STIM [Poitiers] - Signalisation et Transports Ioniques Membranaires
3 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
4 IMCN - Institut de la matière condensée et des nanosciences / Institute of Condensed Matter and Nanosciences
5 CBM - Centre de biophysique moléculaire
6 University of Manchester [Manchester]

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.

Domaines: Chimie thérapeutique; Pharmacie galénique

Romain Barat, Thibaut Legigan, I. Tranoy-Opalinski, Brigitte Renoux, Elodie Peraudeau, et al.. A mechanically interlocked molecular system programmed for the delivery of an anticancer drug. Chemical Science, 2015, 6 (4), pp.2608-2613. ⟨10.1039/c5sc00648a⟩. ⟨hal-03127729⟩