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A galactosidase-responsive doxorubicin-folate conjugate for selective targeting of acute myelogenous leukemia blasts

2013; Elsevier BV; Volume: 37; Issue: 8 Linguagem: Inglês

10.1016/j.leukres.2013.04.026

1873-5835

Jonathan Clarhaut, Sylvain Fraineau, Joëlle Guilhot, Elodie Péraudeau, Isabelle Tranoy‐Opalinski, Mikaël Thomas, Brigitte Renoux, Edouard Randriamalala, Patrick Bois, Aurélien Chatelier, Arnaud Monvoisin, Laurent Cronier, Sébastien Papot, François Guilhot,

Protein Degradation and Inhibitors

Cytarabine combined with an anthracycline or an anthracenedione represents the usual intensive induction therapy for the treatment of AML. However, this protocol induces severe side effects and treatment-related mortality due to the lack of selectivity of these cytotoxic agents. In this paper, we present the study of the first galactosidase-responsive molecular "Trojan Horse" programmed for the delivery of doxorubicin exclusively inside AML blasts over-expressing the folate receptor (FR). This targeting system allows the selective killing of AML blasts without affecting normal endothelial, cardiac or hematologic cells from healthy donors suggesting that FDC could reduce adverse events usually recorded with anthracyclines.