Polymer-drug conjugates for combination anticancer therapy: investigating the mechanism of action.
Pasut, G., Greco, F., Mero, A., Mendichi, R., Fante, C., Green, R. J. and Veronese, F. (2009) Polymer-drug conjugates for combination anticancer therapy: investigating the mechanism of action. Journal of Medicinal Chemistry, 52 (20). pp. 6499-6502. ISSN 0022-2623
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To link to this article DOI: 10.1021/jm900804m
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.