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Article Dans Une Revue Angewandte Chemie International Edition Année : 2020

Drug-sponge lipid nanocarrier for in situ cargo loading and release using dynamic covalent chemistry

Résumé

Currently, drug delivery strategies using nanocarriers (NCs) deal with encapsulation of cargo or its covalently modified prodrug. Here, we propose a concept of reversible pH-controlled capture and delivery of active cargo based on dynamic covalent chemistry inside lipid nano-droplets (nanoemulsions), coined as "drug sponge". We designed a highly lipophilic hydrazide (LipoHD) capable to react with a free cargo-ketone (fluorescent dye and doxorubicin drug) directly inside lipid NCs, yielding lipophilic hydrazone prodrug efficiently captured in the oil core. LipoHD-loaded NCs spontaneously accumulated cargo-ketones, yielding formulations stable against cargo leakage at pH 7.4, and further released their dye/drug cargo at low pH range (5.0-6.8) in solution and live cells. Doxorubicin-loaded drug-sponge NCs showed cytotoxicity in four cancer cell lines and capacity to inhibit tumor growth in subcutaneous xenografts of mice. Finally, unprecedented extraction of dye/drug cargos directly from cells and tissues (i.e. detoxification) was realized by the drug-sponge NCs.
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Dates et versions

hal-03086687 , version 1 (22-12-2020)

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Fei Liu, Yosuke Niko, Redouane Bouchaala, Luc Mercier, Olivier Lefebvre, et al.. Drug-sponge lipid nanocarrier for in situ cargo loading and release using dynamic covalent chemistry. Angewandte Chemie International Edition, In press, ⟨10.1002/anie.202014259⟩. ⟨hal-03086687⟩
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