Preparation of folic acid-modified dextran-5-fluorouracil and its cytotoxicity / 中国药学杂志

ABSTRACT

OBJECTIVE: To synthesize folic acid-modified dextran-5-fluorouracil (FA-DEX-5-Fu) conjugates and investigate its cytotoxicity on cells with folate receptors. METHODS: Dextran (DEX) was selected as the macromolecular carrier and the anti-cancer drug 5-fluorouracil (5-Fu) was selected as a model drug to synthesize 5-Fu-DEX, and then folic acid (FA) was linked into 5-Fu-DEX as the targeting ligand to obtain the conjugate, FA-DEX-5-Fu. UV spectra, IR and ESI-MS were used to identify the structure. UV spectrophotometry was used to determine the contents of FA and 5-Fu in the conjugate. MTT assay was applied to examine the cytotoxicity of free 5-Fu, 5-Fu-DEX and FA-DEX-5-Fu on the Human cervical carcinoma cell line Hela (overexpressing folate receptors) and human lung carcinoma cell line A549 (folate receptor deficient, as negative group). RESULTS: 5-Fu and FA were successfully linked with 5-Fu-DEX as confirmed by UV, IR and ESI-MS spectra.The molar ratio of 5-Fu and FA in the conjutate was 2.71 as determined by UV spectrophotometry. MTT assay results showed the inhibition rate of FA-DEX-5-Fu on Hela cells was much higher than that on A549 cells. And the inhibition rate of FA-DEX-5-Fu on Hela cells was much higher than those of 5-Fu-DEX and free 5-Fu at the same concentration. CONCLUSION: FA-DEX-5-Fu is successfully synthesized and the conjugate shows significant targeting effect against tumor cells overexpressing folate receptors.