Fetuin mediates hepatic uptake of negatively charged nanoparticles via scavenger receptor

• Published in: International journal of pharmaceutics Vol. 329; no. 1; pp. 192 - 198
• Main Authors: Nagayama, Susumu, Ogawara, Ken-ichi, Minato, Keiko, Fukuoka, Yoshiko, Takakura, Yoshinobu, Hashida, Mitsuru, Higaki, Kazutaka, Kimura, Toshikiro
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.02.2007; Elsevier
• Subjects: Adsorption; alpha-Fetoproteins - pharmacokinetics; alpha-Fetoproteins - physiology; Animals; Biological and medical sciences; Cells, Cultured; Fetuin; General pharmacology; Hepatic uptake; Liver - metabolism; Male; Medical sciences; Nanoparticles; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polystyrene nanosphere; Polystyrenes - pharmacokinetics; Rats; Rats, Wistar; Receptor-mediated phagocytosis; Receptors, Scavenger - physiology; Scavenger receptors; Scavenger receptors; Polystyrene nanosphere; Fetuin; Hepatic uptake; Receptor-mediated phagocytosis; Pharmaceutical technology; Nanoparticle; Liver; Radical scavenger; Uptake; Microparticle; Nanosphere; Phagocytosis; Biological receptor
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2006.08.025

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.