TY - JOUR
T1 - Cellular uptake mechanism and intracellular fate of hydrophobically modified glycol chitosan nanoparticles
AU - Nam, Hae Yun
AU - Kwon, Seok Min
AU - Chung, Hyunjin
AU - Lee, Seung Young
AU - Kwon, Seung Hae
AU - Jeon, Hyesung
AU - Kim, Yoonkyung
AU - Park, Jae Hyung
AU - Kim, Joon
AU - Her, Songwook
AU - Oh, Yu Kyoung
AU - Kwon, Ick Chan
AU - Kim, Kwangmeyung
AU - Jeong, Seo Young
N1 - Funding Information:
This research was financially supported by the Real-Time Molecular Imaging Project and Global Research Laboratory Program of MEST and by the Korea Research Foundation Grant funded by the Korea Government (MOEHRD, Basic Research Promotion Fund) (KRF-2007-412-J00304), and by a grant (08162KFDA550) from Korea Food & Drug Administration in 2008. We thank Dr. Kyung Eun Lee at Korea University for obtaining TEM images of our samples.
PY - 2009/5/5
Y1 - 2009/5/5
N2 - 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 5β-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.
AB - 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 5β-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.
KW - Drug delivery system
KW - Endocytosis
KW - Hydrophobically modified glycol chitosan
KW - Intracellular trafficking
KW - Self-assembled nanoparticles
UR - http://www.scopus.com/inward/record.url?scp=63649092083&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2009.01.018
DO - 10.1016/j.jconrel.2009.01.018
M3 - Article
C2 - 19331853
AN - SCOPUS:63649092083
SN - 0168-3659
VL - 135
SP - 259
EP - 267
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 3
ER -