Preparation And Preliminary Cytology Investigation Of Folate Decorated Dextran-5-fluorouracil

5-Fu is an antimetabolite widely used in the chemotherapy of solidtumors. However,5-Fu is quickly catabolized to inactive metabolites,which leads to a very short circulation time in vivo. Moreover, it has seriousside effects such as bone marrow depression, gastrointestinal tract reaction.These limit its antitumor activity and clinical application. To reduce thesystemic toxicities as well as to increase the5-Fu biodistribution to tumor,this paper has designed a kind of targeted drug delivery system.Objective To synthesize folate decorated dextran-5-fluorouracilconjugates and study its ability to inhibit tumor growth in vitro.Methods1. Preparation of FA-DEX-5-FuFirstly, the hydroxy group of DEX was activated by CDI. Secondly,the activated hydroxy group of DEX acted with ethylenediamine to formamino modified DEX (amino-DEX).5-Fu and folate were linked into theDEX through amido link to obtain the conjugate FA-DEX-5-Fu. Itsstructure was identified by ESI-MS, IR.2. MTT assay Human cervical carcinoma cell line Hela (overexpress folate receptor)and human lung carcinoma cell line A549(folate receptor deficient, asnegative group) was served as tested cell. The cell proliferation rates ofFA-DEX-5-Fu were detected by MTT assay. To verify the targeting offolate, the free folate was added.Results1. Folate was successfully coupled with5-Fu-DEX confirmed by UV,ESI-MS, IR.2. The inhibition rate of FA-DEX-5-Fu on Hela cells was muchhigher than that on A549cells, and the inhibition rate of FA-DEX-5-Fu onHela cells overexpressing the folate receptor was much higher than that of5-Fu-DEX and free5-Fu at the same concentration. The inhibition rate ofFA-DEX-5-Fu on A549cells (as negative control) was less than that of free5-Fu. The inhibition rate of FA-DEX-5-Fu on Hela cells was reducedsignificantly due to the addition of free folate. The inhibition rate ofFA-DEX-5-Fu on A549cells did not change significantly after the additionof folate.Conclusions Compared with the5-Fu, the inhibitory action ofFA-DEX-5-Fu on Hela cells significantly increased, and the inhibitoryaction of FA-DEX-5-Fu on Hela cells was reduced result from the additionof free folate. The inhibitory action of FA-DEX-5-Fu on A549cells was notaffected by free folate. The antitumor drug can be deliveried to tumor cells overexpressing folate receptor with the folate-oriented element. It isfeasible to reduce the side effects and achieve tumor-targeted therapy.