Preparation of dendritic graft copolymer consisting of poly-(L-lysine) and arabinogalactan as a hepatocyte specific DNA carrier

Jeong Ung Park, Tsutomu Ishihara, Arihiro Kano, Toshihiro Akaike, Atsushi Maruyama

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The dendritic graft copolymers (PAX) consisting of a poly(L-lysine) (PLL) main chain and grafts of arabinogalactan (AG) were prepared as a liver cell-specific DNA carrier. The copolymers were successfully prepared by reductive amination reaction between a reductive end of AG and ε-amino groups of PLL using NaBH3CN as a catalyst. The fractionation of a low molecular weight fraction (Mn = 25 kDa) from a crude AG (Mn = 33 kDa) was essential for the reaction to proceed. The resulting copolymers were isolated by ultrafiltration from unreacted AG and characterized by 1H NMR and gel permeation chromatography equipped with a multiangle laser light scattering detector (GPC-MALLS). The binding and internalization of DNA to hepatoma cells, HepG2, were considerably enhanced by complexing DNA with PAX copolymers. The interactions between PAX/DNA complexes and HepG2 cells were thoroughly inhibited in the presence of a competitor to asialoglycoprotein receptors (ASGP-R), indicating high specificity of the complex to ASGP-R. Furthermore, the PAX copolymers allowed the expression of the reporter gene. Our results reveal that the PAX copolymers may provide a new research tool for cell-specific gene delivery and eventually enhance gene-therapy technology.

Original languageEnglish
Pages (from-to)353-370
Number of pages18
JournalPreparative Biochemistry and Biotechnology
Volume29
Issue number4
DOIs
Publication statusPublished - Jan 1 1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry

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