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

作者：Barat Romain; Legigan Thibaut; Tranoy Opalinski Isabelle; Renoux Brigitte; Peraudeau Elodie; Clarhaut Jonathan; Poinot Pauline; Fernandes Antony E; Aucagne Vincent; Leigh David A; Papot Sebastien^*

来源：Chemical Science, 2015, 6(4): 2608-2613.

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 beta-galactosidase.

• 出版日期2015