title: Effect of the stability and deformability of self-assembled glycol chitosan nanoparticles on tumor-targeting efficiency.
abstract: To evaluate the tumor targeting efficiency of self-assembled polymeric nanoparticles, four glycol chitosan nanoparticles (CNPs) with different degrees of hydrophobic substitution were prepared by coupling 7.5, 12, 23, and 35 wt.% of 5β-cholanic acid to hydrophilic glycol chitosan polymer (GC). The sizes and zeta-potentials of different CNPs in aqueous condition were not significantly different, but their stability and deformability were greatly dependent upon the degree of substitution (DS) of 5β-cholanic acid. With an increase in hydrophobicity, CNPs became more stable and rigid, as characterized by SDS-PAGE and filtration tests. To compare with CNPs, linear GC and polystyrene nanoparticles (PSNPs) were employed as controls. In vivo tumor accumulation of Cy5.5-labeled linear GC, polystyrene nanoparticles (PSNPs) and CNPs were monitored in flank tumors and liver tumor-bearing mice models using near-infrared fluorescence (NIRF) imaging systems. CNPs displayed higher tumor accumulation than GC and PSNPs via the enhanced permeability and retention (EPR) effect. Interestingly, CNPs containing 23 wt.% of 5β-cholanic acid (CNP-23%) showed the highest tumor-targeting efficiency compared to other CNPs. As exemplified in this study, the stability of CNP-23% is better than CNP-7.5% and CNP-12% containing 7.5 wt.% and 12 wt.% of 5β-cholanic acid, respectively, and the deformability of CNP-23% is better than that of CNP-35% containing 35 wt.% of 5β-cholanic acid. We proposed that the superior tumor-targeting efficiency of CNP-23% is mainly due to their balanced stability and deformability in vivo. This study demonstrates that the degree of hydrophobic substitution of self-assembled nanoparticles could determine their stability and deformability. Importantly, they were founded to be the key factors which affect their tumor-targeting efficiency in vivo, and so that these factors should be highly considered during developing nanoparticles for tumor-targeted imaging or drug delivery.
authors: Department of Life and Nanopharmaceutical Science, Kyung Hee University, 1 Hoegi-ding, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors: Jin Hee
authors: JH
authors: Na
authors: Seung-Young
authors: SY
authors: Lee
authors: Sangmin
authors: S
authors: Lee
authors: Heebeom
authors: H
authors: Koo
authors: Kyung Hyun
authors: KH
authors: Min
authors: Seo Young
authors: SY
authors: Jeong
authors: Soon Hong
authors: SH
authors: Yuk
authors: Kwangmeyung
authors: K
authors: Kim
authors: Ick Chan
authors: IC
authors: Kwon
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000008:administration & dosage; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry*; D002793:Cholic Acids / Q000737:chemistry; D004396:Coloring Agents / Q000008:administration & dosage; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D004355:Drug Stability; D019073:HT29 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D002793:Cholic Acids; D004396:Coloring Agents; D004337:Drug Carriers; C118638:glycol-chitosan; D048271:Chitosan; C007036:cholanic acid