title: Polymer-drug conjugates for combination anticancer therapy: investigating the mechanism of action.
abstract: We developed a family of polymer-drug conjugates carrying the combination of the anticancer agent epirubicin (EPI) and nitric oxide (NO). EPI-PEG-(NO)8, carrying the highest content of NO, displayed greater activity in Caco-2 cells while it decreased toxicity against endothelium cells and cardiomyocytes with respect to free EPI. FACS and confocal microscopy confirmed conjugates internalization. Light scattering showed formation of micelle whose size correlated with internalization rate. EPI-PEG-(NO)8 showed increased bioavailability in mice compared to free EPI.
authors.affiliation: Department of Pharmaceutical Sciences, Via F. Marzolo 5, University of Padua, 35100 Padova, Italy. gianfranco.pasut@unipd.it
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Pasut
authors.forename: Francesca
authors.initials: F
authors.lastname: Greco
authors.forename: Anna
authors.initials: A
authors.lastname: Mero
authors.forename: Raniero
authors.initials: R
authors.lastname: Mendichi
authors.forename: Cristina
authors.initials: C
authors.lastname: Fante
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Green
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Veronese
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001692:Biological Transport; D045744:Cell Line, Tumor; D015251:Epirubicin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D050356:Lipid Metabolism; D051379:Mice; D009569:Nitric Oxide / Q000737:chemistry* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry*; D012996:Solutions; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D012996:Solutions; D009569:Nitric Oxide; D011092:Polyethylene Glycols; D015251:Epirubicin