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Selective and Effective Cytotoxicity of Folic Acidconjugated Cholesteryl Pullulan Hydrogel Nanoparticles Complexed with Doxorubicin inIn Vitro and In Vivo Studies

Department of Transplantation and Digestive Surgery, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki City, 852-8102, Japan masaaki_h1{at}hotmail.com

Takashi Kanematsu

Department of Transplantation and Digestive Surgery, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki City, 852-8102, Japan

Kazutoshi Ushio

Department of Applied Chemistry and Biotechnology, Niihama National College of Technology

Junzo Sunamoto

We previously reported that cholesteryl pullulan (CHP) derivatives were effective carriers drug delivery systems in targeting cancer cells. We have now synthesized folic acid-conjugated CHP hydrogel nanoparticles (FACHP). FA-CHP complexed with the anticancer drug doxorubicin (DOX) show a higher cytotoxicity than CHP complexed with DOX in in vitro studies. The expression of a folate receptor (FR) is elevated in many cancers; in this case, confocal image analysis revealed that FA-CHP complexed with DOX exhibited greater cellular uptake than CHP complexed with DOX in human epidermal carcinoma (KB) cells over-expressing surface FR. In vivo studies showed that the increase of tumor volume in a nude mice xenograft model was significantly suppressed. Accordingly, FA-CHP may be an effective vehicle for the delivery of anticancer drugs and has a potential application in the treatment of overexpressing FR solid tumor cells.

Key Words: folate receptor • drug targeting • cholesteryl pullulan • doxorubicin

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