Fetuin mediates hepatic uptake of negatively charged nanoparticles via scavenger receptor

Susumu Nagayama, Ken ichi Ogawara, Keiko Minato, Yoshiko Fukuoka, Yoshinobu Takakura, Mitsuru Hashida, Kazutaka Higaki, Toshikiro Kimura

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

Abstract

We tried to evaluate the possible involvement of fetuin in the scavenger receptors (SRs)-mediated hepatic uptake of polystyrene nanospheres with the size of 50 nm (NS-50), which has surface negative charge (zeta potential = -21.8 ± 2.3 mV). The liver perfusion studies in rats revealed that the hepatic uptake of NS-50 pre-coated with fetuin (NS-50-fetuin) was significantly inhibited by poly inosinic acid (poly I), a typical inhibitor of SRs, whereas that of plain NS-50 or NS-50 pre-coated with BSA (NS-50-BSA) was not. The uptake of NS-50-fetuin by cultured Kupffer cells was also significantly inhibited by poly I, and anti-class A scavenger receptors (SR-A) antibody, suggesting that fetuin on NS-50 mediated the recognition and internalization of NS-50 by Kupffer cells and at least SR-A would be responsible for the uptake. Taken that Western blot analysis confirmed that fetuin certainly adsorbed on the surface of NS-50 after the incubation of NS-50 with serum, the results obtained in the present study indicate that fetuin would be one of the serum proteins that were substantially involved in the hepatic uptake of NS-50 via SRs.

Original languageEnglish
Pages (from-to)192-198
Number of pages7
JournalInternational Journal of Pharmaceutics
Volume329
Issue number1-2
DOIs
Publication statusPublished - Feb 1 2007

Keywords

  • Fetuin
  • Hepatic uptake
  • Polystyrene nanosphere
  • Receptor-mediated phagocytosis
  • Scavenger receptors

ASJC Scopus subject areas

  • Pharmaceutical Science

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