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Folate-Modified Cholesterol-Bearing Pullulan, a New Cancer-Targeted Nanoparticle Drug Carrier: Synthesis and Applications

Kazutoshi Ushio

Niihama National College of Technology, Department of Applied Chemistry and Biotechnology, 7–1 Yagumo, Niihama, Ehime 792–8580, Japanushio{at}chem.niihama-nct.ac.jp

Douglas T. Lai

Niihama National College of Technology, Department of Applied Chemistry and Biotechnology, 7–1 Yagumo, Niihama, Ehime 792–8580, Japan

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.

Key Words: drug carrier • anticancer • folate • CHP • nanoparticle

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