Tumor-targeted drug delivery by folate conjugated amphiphiles

Drug delivery by folate conjugated amphiphiles Abstract A series of amphiphilic conjugates of folic acid and aliphatic fatty acids was designed to serve as targeted drug delivery carriers for anticancer agents. The effectiveness of targeted delivery of amphiphile was evaluated using folate receptor positive HeLa cells and Caco-2 cells that do not express folate receptor. Wild type HeLa cells were found to have 40fold greater folate receptor (FRα) expression than Caco-2 cells. Amphiphile uptake was studied by the internalization of 7-amino-4carboxymethyl coumarin labeled fluorescent amphiphilic conjugate in FRknockdown HeLa, and Caco-2 cells at 37°C and 4°C, respectively. siRNA specific for FRα was used to knockdown the receptor in HeLa cells by 75% and these modified cells were used as the control in determining the specificity of amphiphiles uptake. Wild type HeLa cells internalized twice as much fluorescent amphiphiles as compared to all other treatment groups at 37°C. Paclitaxel, a lipophilic antitumor agent was used as a model compound to evaluate the efficacy of three homologous series of amphiphile conjugates as targeted carriers in HeLa and Caco-2 cells. The amphiphiles were non-toxic to both cell lines at the concentrations lower than 100μM. Amphiphilic micelle containing paclitaxel exhibited significantly lower IC 50 values in HeLa cells when compared to free drug and untargeted amphiphile micelles. The data from the current studies demonstrated the feasibility of using folic acid conjugated amphiphiles to selectively deliver drugs to FRα positive cancer cells.