Abstract
It has been reported that nanoparticles (NPs) prepared by hydrophobically-modified polymers could accumulate passively in the tumor tissue; however, their cellular uptake mechanism and intercellular trafficking pathway have never been understood. This study was designed to address these concerns, using NPs prepared by a hydrophobically-modified chitosan (N-palmitoyl chitosan, NPCS). Molecular dynamic simulations found that a degree of substitution (DS) of 5% of palmitoyl groups on its backbone was sufficient to allow NPCS to form NPs, due to a significant increase in the intra- and intermolecular hydrophobic interactions. With an increase of DS, there were more palmitoyl groups present on the surface of NPs which were then able to interact with the cell membranes. A greater extent of cellular uptake of NPCS NPs was observed with increasing the DS on NPCS. The internalization of NPCS NPs was clearly related with the lipid raft-mediated routes; with increasing the DS on NPCS, the caveolae-mediated endocytosis became more important. The results obtained in the intracellular trafficking study showed that NPCS NPs entered cells via caveolae and transiently localized to caveosomes before trafficking to the endosomal pathway. These results suggest that the prepared NCPS NPs may serve as a carrier for intracellular delivery of therapeutic agents.
Original language | English |
---|---|
Pages (from-to) | 152-159 |
Number of pages | 8 |
Journal | Journal of Controlled Release |
Volume | 146 |
Issue number | 1 |
DOIs | |
Publication status | Published - Aug 2010 |
Externally published | Yes |
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Keywords
- Caveolae
- Endocytosis
- Internalization pathway
- Molecular dynamic simulation
- N-palmitoyl chitosan
ASJC Scopus subject areas
- Pharmaceutical Science
Cite this
The characteristics, cellular uptake and intracellular trafficking of nanoparticles made of hydrophobically-modified chitosan. / Chiu, Ya Ling; Ho, Yi Cheng; Chen, Yu Ming; Peng, Shu Fen; Ke, Cherng Jyh; Chen, Ko Jie; Mi, Fwu Long; Sung, Hsing Wen.
In: Journal of Controlled Release, Vol. 146, No. 1, 08.2010, p. 152-159.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The characteristics, cellular uptake and intracellular trafficking of nanoparticles made of hydrophobically-modified chitosan
AU - Chiu, Ya Ling
AU - Ho, Yi Cheng
AU - Chen, Yu Ming
AU - Peng, Shu Fen
AU - Ke, Cherng Jyh
AU - Chen, Ko Jie
AU - Mi, Fwu Long
AU - Sung, Hsing Wen
PY - 2010/8
Y1 - 2010/8
N2 - It has been reported that nanoparticles (NPs) prepared by hydrophobically-modified polymers could accumulate passively in the tumor tissue; however, their cellular uptake mechanism and intercellular trafficking pathway have never been understood. This study was designed to address these concerns, using NPs prepared by a hydrophobically-modified chitosan (N-palmitoyl chitosan, NPCS). Molecular dynamic simulations found that a degree of substitution (DS) of 5% of palmitoyl groups on its backbone was sufficient to allow NPCS to form NPs, due to a significant increase in the intra- and intermolecular hydrophobic interactions. With an increase of DS, there were more palmitoyl groups present on the surface of NPs which were then able to interact with the cell membranes. A greater extent of cellular uptake of NPCS NPs was observed with increasing the DS on NPCS. The internalization of NPCS NPs was clearly related with the lipid raft-mediated routes; with increasing the DS on NPCS, the caveolae-mediated endocytosis became more important. The results obtained in the intracellular trafficking study showed that NPCS NPs entered cells via caveolae and transiently localized to caveosomes before trafficking to the endosomal pathway. These results suggest that the prepared NCPS NPs may serve as a carrier for intracellular delivery of therapeutic agents.
AB - It has been reported that nanoparticles (NPs) prepared by hydrophobically-modified polymers could accumulate passively in the tumor tissue; however, their cellular uptake mechanism and intercellular trafficking pathway have never been understood. This study was designed to address these concerns, using NPs prepared by a hydrophobically-modified chitosan (N-palmitoyl chitosan, NPCS). Molecular dynamic simulations found that a degree of substitution (DS) of 5% of palmitoyl groups on its backbone was sufficient to allow NPCS to form NPs, due to a significant increase in the intra- and intermolecular hydrophobic interactions. With an increase of DS, there were more palmitoyl groups present on the surface of NPs which were then able to interact with the cell membranes. A greater extent of cellular uptake of NPCS NPs was observed with increasing the DS on NPCS. The internalization of NPCS NPs was clearly related with the lipid raft-mediated routes; with increasing the DS on NPCS, the caveolae-mediated endocytosis became more important. The results obtained in the intracellular trafficking study showed that NPCS NPs entered cells via caveolae and transiently localized to caveosomes before trafficking to the endosomal pathway. These results suggest that the prepared NCPS NPs may serve as a carrier for intracellular delivery of therapeutic agents.
KW - Caveolae
KW - Endocytosis
KW - Internalization pathway
KW - Molecular dynamic simulation
KW - N-palmitoyl chitosan
UR - http://www.scopus.com/inward/record.url?scp=77955276767&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955276767&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2010.05.023
DO - 10.1016/j.jconrel.2010.05.023
M3 - Article
C2 - 20580915
AN - SCOPUS:77955276767
VL - 146
SP - 152
EP - 159
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 1
ER -