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Galactosylated low molecular weight chitosan as a carrier delivering oligonucleotides to Kupffer cells instead of hepatocytes in vivo
Author(s) -
Dong Lei,
Gao Shuying,
Diao Huajia,
Chen Jiangning,
Zhang Junfeng
Publication year - 2007
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.31328
Subject(s) - asialoglycoprotein receptor , endocytosis , in vivo , kupffer cell , in vitro , lectin , microbiology and biotechnology , biology , receptor , biochemistry , immunology , hepatocyte
The in vivo cellular localization of oligodeoxynucleotides (ODNs) delivered by galactosylated low molecular weight chitosan (gal‐LMWC) was investigated. The gal‐LMWCs preference for Kupffer cells was confirmed by in vivo and in vitro experiments. Furthermore, asialoglycoprotein receptor (ASGPr) was studied as a possible surface lectin which may involved in the endocytosis of the gal‐LMWC/ODN complexes. Results showed that the gal‐LMWC/ODN complex accumulated in liver when injected intravenously (i.v.). Further studies revealed that 50.6% of the complex was taken up by Kupffer cells in liver, 33.2% was taken up by endothelial cells, and only 16.2% of the complex was taken up by parenchymal cells. In vitro results also confirmed the affinity of gal‐LMWC to murine Kupffer cells. Inhibition of the transfection by lactose and N ‐acetyl galactosamine (GalNAc) suggested that the particles might enter macrophages via ASGPr and the inhibition by LMWC implied that there might be other lectins involved in the endocytosis. In summary, our studies revealed that gal‐LMWC/ODN complex is inclined to enter into Kupffer cells rather than into liver parenchymal cells in vivo . Galactosylation may not be a proper means for targeting chitosan/DNA nanoparticles to hepatocytes but it does have the potential to be a Kupffer cells targeting strategy especially for delivering drugs for antiinflammation. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008