title: A galactosidase-responsive doxorubicin-folate conjugate for selective targeting of acute myelogenous leukemia blasts.
abstract: 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.
authors.affiliation: INSERM CIC 0802, Poitiers, France. jonathan.clarhaut@univ-poitiers.fr
authors.forename: Jonathan
authors.initials: J
authors.lastname: Clarhaut
authors.forename: Sylvain
authors.initials: S
authors.lastname: Fraineau
authors.forename: Joëlle
authors.initials: J
authors.lastname: Guilhot
authors.forename: Elodie
authors.initials: E
authors.lastname: Peraudeau
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tranoy-Opalinski
authors.forename: Mikaël
authors.initials: M
authors.lastname: Thomas
authors.forename: Brigitte
authors.initials: B
authors.lastname: Renoux
authors.forename: Edouard
authors.initials: E
authors.lastname: Randriamalala
authors.forename: Patrick
authors.initials: P
authors.lastname: Bois
authors.forename: Aurélien
authors.initials: A
authors.lastname: Chatelier
authors.forename: Arnaud
authors.initials: A
authors.lastname: Monvoisin
authors.forename: Laurent
authors.initials: L
authors.lastname: Cronier
authors.forename: Sébastien
authors.initials: S
authors.lastname: Papot
authors.forename: François
authors.initials: F
authors.lastname: Guilhot
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D001752:Blast Crisis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D058975:Folate Receptor 1 / Q000235:genetics / Q000378:metabolism; D058976:Folate Receptor 2 / Q000235:genetics / Q000378:metabolism; D005492:Folic Acid / Q000737:chemistry; D057809:HEK293 Cells; D018922:HL-60 Cells; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult; D001616:beta-Galactosidase / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; D058975:Folate Receptor 1; D058976:Folate Receptor 2; D004317:Doxorubicin; D005492:Folic Acid; D001616:beta-Galactosidase