Madegard Léa, Girard Melissa, Blochouse Estelle, Riss Yaw Benjamin, Palazzolo Alberto, Laquembe Mélanie, Audisio Davide, Poinot Pauline, Papot Sébastien, Taran Frédéric
Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), 91191, Gif-sur-Yvette, France.
Equipe labellisée Ligue contre le cancer, Université de Poitiers, UMR CNRS 7285, Institut de Chimie des Milieux et Matériaux de Poitiers (IC2MP), 4 rue Michel Brunet, TSA 51106, 86073, Poitiers cedex 9, France.
Angew Chem Int Ed Engl. 2025 Feb 17;64(8):e202422627. doi: 10.1002/anie.202422627. Epub 2025 Jan 7.
The development of innovative strategies enabling chemical reactions in living systems is of great interest for exploring and manipulating biological processes. Herein, we present a pioneering approach based on both bioorthogonal and confined chemistry for intracellular drug synthesis. Exploiting a click-to-release reaction, we engineered nanoparticles capable of synthesizing drugs within cellular environments through bioorthogonal reactions with cyclooctynes. Proof of concept experiments showed that this new approach could be successfully applied to the synthesis of the FDA-approved Sorafenib within cancer cells. The integration of bioorthogonal and confined chemistry not only offers exciting prospects for advancing therapeutic strategies but also opens up new avenues for exploring non-natural reactions within living systems. This innovative approach represents a fundamental extension of the biorthogonal chemistry concept and holds great promise for pioneering developments in therapeutic applications.
开发能够在生物系统中实现化学反应的创新策略，对于探索和操纵生物过程具有极大的意义。在此，我们提出一种基于生物正交化学和受限化学的开创性方法，用于细胞内药物合成。利用点击释放反应，我们设计了纳米颗粒，使其能够通过与环辛炔的生物正交反应在细胞环境中合成药物。概念验证实验表明，这种新方法可以成功应用于在癌细胞内合成美国食品药品监督管理局（FDA）批准的索拉非尼。生物正交化学和受限化学的结合不仅为推进治疗策略提供了令人兴奋的前景，也为探索生物系统中的非天然反应开辟了新途径。这种创新方法代表了生物正交化学概念的根本扩展，在治疗应用的开创性发展方面具有巨大潜力。
