Journal
ORGANIC & BIOMOLECULAR CHEMISTRY
Volume 11, Issue 41, Pages 7129-7133Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c3ob41536h
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Funding
- CNRS
- La Ligue Nationale contre le Cancer
- Association Cent pour Sang la Vie
- Agence Nationale de la Recherche (ANR-Blanc, ProTarget)
- Region Poitou-Charentes
- Region Centre
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The rise of chemical biology has led to the development of sophisticated molecular devices designed to explore and manipulate biological processes. Within this framework, we developed the first chemical system programmed for the selective internalization and subsequent enzyme-catalyzed double release of bioactive compounds inside a targeted population of cells. This system is composed of five distinct units including a targeting ligand, an enzymatic trigger, a self-immolative linker and two active compounds articulated around a chemical amplifier. Designed as such, this molecular assembly is capable in an autonomous manner to recognize a selected population of cells, penetrate into the intracellular medium through endocytosis and transform a single enzymatic activation step into the release of two active units. Demonstrating that an enzyme-catalyzed amplification process can occur spontaneously under the conditions prevailing within the cells could be an important step toward the development of innovative molecular systems fora diverse range of applications spanning drug delivery biological sensors and diagnostics.
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