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In situ targeted activation of an anticancer agent using ultrasound-triggered release of composite droplets
Marine Bezagu1, Jonathan Clarhaut2, Brigitte Renoux3
1Laboratoire de Chimie Organique, Institute of Chemistry, Biology and Innovation (CBI) - ESPCI Paris/CNRS (UMR8231)/PSL Research University, 10 rue Vauquelin, 75231 Paris Cedex 05, France; Laboratoire de Microfluidique, MEMS et Nanostructures, ESPCI Paris, CNRS (UMR Gulliver 7083), 10 rue Vauquelin, 75231 Paris Cedex 05, France.
Abstract:
The efficiency of a drug is usually highly dependent on the way it is administered or delivered. As such, targeted-therapy, which requires conceiving drug-delivery vehicles that will change their state from a relatively stable structure with a very slow leak-rate to an unstable structure with a fast release, clearly improves the pharmacokinetics, the absorption, the distribution, the metabolism and the therapeutic index of a given drug. In this context, we have developed a particularly effective double stimuli-responsive drug-delivery method allowing an ultrasound-induced release of a monomethylauristatin E-glucuronide prodrug and its subsequent activation by a β-glucuronidase. This led to an increase of cytotoxicity of about 80% on cancer cells.