A combinatorial approach involving E. coli cytosine deaminase and 5-fluorocytosine-nanoparticles as an enzyme-prodrug therapeutic method for highly substrate selective in situ generation of 5-fluorouracil

Abstract

Enzyme-prodrug combination is a recognized therapeutic strategy for the treatment of cancer cells. Cytosine deaminases (CD) are non-mammalian proteins perceived to convert the prodrug 5-fluorocytosine (5-FC), into the active antitumor agent 5-fluorouracil (5-FU). In this study, we have synthesized 5-FC as well as 5-FU loaded chitosan-silver nanoparticles in a green synthesis approach, with high yield. The size of the nanoparticles was ascertained to be below 25 nm, thus proficient in penetrating cells. Investigation in human breast carcinoma cell line MDA-MB-468 manifested potent cytotoxicity for 5-FU nanoparticles as compared to the prodrug, 5-FC nanoparticles. E. coli CD (ECD) effectively hydrolyzes 5-FC into 5-FU but was inert to silver nanoparticles as well as 5-FU loaded nanoparticles.