Folate-modified cholesterol-bearing pullulan, a new cancer-targeted nanoparticle drug carrier: Synthesis and applications

Folate-modified cholesterol-bearing pullulan (FA-CHP) was synthesized by the reaction of folic acid beta-2-aminoethylamide and 4-nitrophenyl chloroformate-activated cholesterol-bearing pullulan. The substitution ratio was estimated as 10% per glucoside units. Several combinations of FA-CHP, unmodified cholesterol-bearing pullulan (CHP) and doxorubicin (DOX) mixtures were tested for cancer-selective cytotoxicity in vitro. A combination of FA-CHP/CHP/DOX of 1:4:0.02 (weight ratio) had aggressive and selective effects on human epidermoid cancer KB cells, known to express a high level of folate receptor, while the same nanoparticle mixture had a weak effect on the growth of normal human fetal lung fibroblast TIG-1-20 cells.