Jong-Ho Kim^{a, 1}, Yoo-Shin Kim^{b, 1}, Kyeongsoon Park^a, Seulki Lee^a, Hae Yun Nam^{a, c}, Kyung Hyun Min^{a, d}, Hyung Gon Jo^{a, d}, Jae Hyung Park^c, Kuiwon Choi^a, Seo Young Jeong^d, Rang-Woon Park^b, In-San Kim^b, Kwangmeyung Kim^a and Ick Chan Kwon<sup>a

a</sup> Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea
^b Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, 101 Dongin-dong, Jung-gu, Daegu 700-422, South Korea
^c Departments of Advanced Polymer and Nanopharmaceutical Sciences, Kyung Hee University, Gyeonggi-do 449-701, South Korea
^d Department of Life and Nanopharmaceutical Science, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, South Korea

Corresponding author : Kwangmeyung Kim
Tel.: +82 2 958 5916; fax: +82 2 958 5909.

¹ These authors contributed equally to this paper.

Abstract
To make a tumor targeting nano-sized drug delivery system, biocompatible and biodegradable glycol chitosan (M_w = 250 kDa) was modified with hydrophobic cholanic acid. The resulting hydrophobically modified glycol chitosans (HGCs) that formed nano-sized self-aggregates in an aqueous medium were investigated as an anticancer drug carrier in cancer treatment. Insoluble anticancer drug, cisplatin (CDDP), was easily encapsulated into the hydrophobic cores of HGC nanoparticles by a dialysis method, wherein the drug loading efficiency was about 80%. The CCDP-encapsulated HGC (CDDP-HGC) nanoparticles were well-dispersed in aqueous media and they formed a nanoparticles structure with a mean diameter about 300?500 nm. As a nano-sized drug carrier, the CDDP-HGC nanoparticles released the drug in a sustained manner for a week and they were also less cytotoxic than was free CDDP, probably because of sustained release of CDDP from the HGC nanoparticles. The tumor targeting ability of CDDP-HGC nanoparticles was confirmed by in vivo live animal imaging with near-infrared fluorescence Cy5.5-labeled CDDP-HGC nanoparticles. It was observed that CDDP-HGC nanoparticles were successfully accumulated by tumor tissues in tumor-bearing mice, because of the prolonged circulation and enhanced permeability and retention (EPR) effect of CDDP-HGC nanoparticles in tumor-bearing mice. As expected, the CDDP-HGC nanoparticles showed higher antitumor efficacy and lower toxicity compared to free CDDP, as shown by changes in tumor volumes, body weights, and survival rates, as well as by immunohistological TUNEL assay data. Collectively, the present results indicate that HGC nanoparticles are a promising carrier for the anticancer drug CDDP.

Keywords: Hydrophobically modified glycol chitosan; Self-assembled nanoparticles; Cisplatin; Drug delivery system; Passive tumor targeting; In vivo antitumor efficacy