Kyeongsoon Parka, 1, Jong-Ho Kima, 1, Yun Sik Nama, Seulki Leea, Hae Yun Nama, b, Kwangmeyung Kima, Jae Hyung Parkb, In-San Kimc, Kuiwon Choia, Sang Yoon Kimd, Ick Chan Kwona,*
a Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea
b Department of Advanced Polymer and Nanopharmaceutical Sciences, College of Environment and Applied Chemistry, KyungHee University, Gyeonggi-do 449-710, South Korea
c Department of Biochemistry, School of Medicine, Kyungpook National University, 101 Dong-In 2, Jung-gu, Daegu 700-422, South Korea
d Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736, South Korea
*Corresponding author : Ick Chan Kwon
1 These authors contributed equally to this paper.
To improve the in vivo tumor targeting characteristics of polymeric nanoparticles, three glycol chitosan (GC-20 kDa, GC-100 kDa, and GC-250 kDa) derivatives with different molecular weights were modified with cholanic acid at the same molar ratio. The resulting amphiphilic glycol chitosan?cholanic acid conjugates self-assembled to form glycol chitosan nanoparticles (GC-20 kDa-NP, GC-100 kDa-NP, and GC-250 kDa-NP) under aqueous conditions. The physicochemical properties of all three glycol chitosan nanoparticles, including degree of substitution with cholanic acid, surface charge, particle size and in vitro stability, were similar regardless of molecular weight. In vivo tissue distribution, time-dependent excretion, and tumor accumulation of glycol chitosan nanoparticles labeled with the near-infrared (NIR) fluorophore, Cy5.5, were monitored in SCC7 tumor-bearing mice, using NIR fluorescence imaging systems. Glycol chitosan nanoparticles displayed prolonged blood circulation time, decreased time-dependent excretion from the body, and elevated tumor accumulation with increasing polymer molecular weight. The results collectively suggest that high molecular weight glycol chitosan nanoparticles remain for longer periods in the blood circulation, leading to increased accumulation at the tumor site. Accordingly, we propose that enhanced tumor targeting by high molecular weight glycol chitosan nanoparticles is related to better in vivo stability, based on a pharmacokinetic improvement in blood circulation time.
Keywords : Glycol chitosan nanoparticle; Polymer molecular weight; Tissue distribution; Tumor targeting