Tumor-targeted drug delivery by folate conjugated amphiphiles

A series of amphiphilic conjugates offolic acid and aliphatic fatty acids was designedto serve as targeted drug delivery carriers foranticancer agents. The effectiveness of targeteddelivery of amphiphile was evaluated using folatereceptor positive HeLa cells and Caco-2 cells thatdo not express folate receptor. Wild type HeLacells were found to have 40- fold greater folatereceptor - (FRa) expression than Caco-2 cells.Amphiphile uptake was studied by theinternalization of 7-amino-4carboxymethylcoumarin labeled fluorescent amphiphilicconjugate in FR- knockdown HeLa, and Caco-2cells at 37¡C and 4¡C, respectively. siRNAspecific for FRa was used to knockdown thereceptor in HeLa cells by 75% and these modifiedcells were used as the control in determining thespecificity of amphiphiles uptake. Wild typeHeLa cells internalized twice as much fluorescentamphiphiles as compared to all other treatmentgroups at 37¡C. Paclitaxel, a lipophilic antitumoragent was used as a model compound toevaluate the efficacy of three homologous seriesof amphiphile conjugates as targeted carriers inHeLa and Caco-2 cells. The amphiphiles werenon-toxic to both cell lines at the concentrationslower than 100µM. Amphiphilic micellecontaining paclitaxel exhibited significantlylower IC50 values in HeLa cells when comparedto free drug and untargeted amphiphile micelles.The data from the current studies demonstratedthe feasibility of using folic acid conjugatedamphiphiles to selectively deliver drugs to FRapositive cancer cells