title: Cellular uptake mechanism and intracellular fate of hydrophobically modified glycol chitosan nanoparticles.
abstract: Polymeric nanoparticle-based carriers are promising agents for the targeted delivery of therapeutics to the intracellular site of action. To optimize the efficacy in delivery, often the tuning of physicochemical properties (i.e., particle size, shape, surface charge, lipophilicity, etc.) is necessary, in a manner specific to each type of nanoparticle. Recent studies showed an efficient tumor targeting by hydrophobically modified glycol chitosan (HGC) nanoparticles through the enhanced permeability and retention (EPR) effect. As a continued effort, here the investigations on the cellular uptake mechanism and the intracellular fate of the HGC nanoparticles are reported. The HGC nanoparticle, prepared by a partial derivatization of the free amino groups of glycol chitosan (GC) with 5beta-cholanic acid, had a globular shape with the average diameter of 359 nm and the zeta potential of ca. 22 mV. Interestingly, these nanoparticles showed an enhanced distribution in the whole cells, compared to the parent hydrophilic GC polymers. In vitro experiments with endocytic inhibitors suggested that several distinct uptake pathways (e.g., clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macropinocytosis) are involved in the internalization of HGC. Some HGC nanoparticles were found entrapped in the lysosomes upon entry, as determined by TEM and colocalization studies. Given such favorable properties including low toxicity, biocompatibility, and fast uptake by several nondestructive endocytic pathways, our HGC nanoparticles may serve as a versatile carrier for the intracellular delivery of therapeutic agents.
authors.affiliation: Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South South Korea.
authors.forename: Hae Yun
authors.initials: HY
authors.lastname: Nam
authors.forename: Seok Min
authors.initials: SM
authors.lastname: Kwon
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Chung
authors.forename: Seung-Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Seung-Hae
authors.initials: SH
authors.lastname: Kwon
authors.forename: Hyesung
authors.initials: H
authors.lastname: Jeon
authors.forename: Yoonkyung
authors.initials: Y
authors.lastname: Kim
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
authors.forename: Joon
authors.initials: J
authors.lastname: Kim
authors.forename: Songwook
authors.initials: S
authors.lastname: Her
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Jeong