Polymer-drug conjugates for combination anticancer therapy: investigating the mechanism of action.
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.
Pasut
Gianfranco
G
Department of Pharmaceutical Sciences, Via F. Marzolo 5, University of Padua, 35100 Padova, Italy. gianfranco.pasut@unipd.it
Greco
Francesca
F
Mero
Anna
A
Mendichi
Raniero
R
Fante
Cristina
C
Green
Rebecca J
RJ
Veronese
Francesco M
FM
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
D000970:Antineoplastic Agents; D012996:Solutions; D009569:Nitric Oxide; D011092:Polyethylene Glycols; D015251:Epirubicin