Enhancing Anticancer Efficacy of Doxifluridine Using Polymeric Micelles in Human Colon Cancer Cells

To lessen lethal side effects of 5-FU therapy on normal health cells, doxifluridine (prodrug of 5-FU) was used as the initiator directly in ring-opening polymerization of epsilon-caprolactone to form hydrophobic doxiflurine-poly(epsilon-caprolactone) (doxifluridine-PCL) which was further grafted with hydrophilic chitosan to fabricate amphiphilic polymer. Self-assembled micellar nanoparticles made of this amphiphilic polymer (i.e., doxifluridine-PCL-chitosan) further formed a complex with thymidine phosphorylase (TP) cDNA encoded plasmid via its cationic hydrophilic segment - chitosan. After HT-29 colon cancer cells were targeted with such polymeric prodrug micelles, doxifluridine was converted into 5-FU by TP overexpressed via gene transfection in cancer cells. Our result showed that slowly released cytotoxic agent 5-FU in HT-29 cells resulted in enhanced anticancer activity.