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

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Liu, Fei | Niko, Yosuke | Bouchaala, Redouane | Mercier, Luc | Lefebvre, Olivier | Andreiuk, Bohdan | Vandamme, Thierry | Goetz, Jacky, G | Anton, Nicolas | Klymchenko, Andrey

Edité par CCSD ; Wiley-VCH Verlag -

International audience. 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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