TY - JOUR
T1 - Important role of serum proteins associated on the surface of particles in their hepatic disposition
AU - Furumoto, Kentaro
AU - Ogawara, Ken-ichi
AU - Nagayama, Susumu
AU - Takakura, Yoshinobu
AU - Hashida, Mitsuru
AU - Higaki, Kazutaka
AU - Kimura, Toshikiro
N1 - Funding Information:
This work was supported in part by a Grant-in Aid for Encouragement of Young Scientists from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
PY - 2002/9/18
Y1 - 2002/9/18
N2 - To elucidate the important factors for the difference in the hepatic disposition between polystyrene nanospheres with a size of 50 nm (NS-50) and lecithin-coated NS-50 (LNS-50), the liver perfusion studies and the in vitro uptake studies using the cultured Kupffer cells were performed. It was suggested that opsonin-mediated phagocytosis is not significantly involved in the hepatic disposition of LNS-50 in the presence of serum, whereas its involvement in the hepatic uptake of NS-50 was clearly demonstrated. Western blot analysis showed that IgG, complement C3, and fibronectin, well-known opsonins in the serum, adsorbed on the surface of NS-50 in larger amount than on the surface of LNS-50. On the other hand, serum albumin, which was suggested to function as a dysopsonin for the hepatic disposition of NS-50, was associated with both spheres almost to the same extent. These findings suggest that the hepatic disposition of LNS-50 at lower level should be ascribed to the less amount of serum opsonins associated on the surface and that the serum proteins associated with these spheres should be important as a determinant for their hepatic disposition.
AB - To elucidate the important factors for the difference in the hepatic disposition between polystyrene nanospheres with a size of 50 nm (NS-50) and lecithin-coated NS-50 (LNS-50), the liver perfusion studies and the in vitro uptake studies using the cultured Kupffer cells were performed. It was suggested that opsonin-mediated phagocytosis is not significantly involved in the hepatic disposition of LNS-50 in the presence of serum, whereas its involvement in the hepatic uptake of NS-50 was clearly demonstrated. Western blot analysis showed that IgG, complement C3, and fibronectin, well-known opsonins in the serum, adsorbed on the surface of NS-50 in larger amount than on the surface of LNS-50. On the other hand, serum albumin, which was suggested to function as a dysopsonin for the hepatic disposition of NS-50, was associated with both spheres almost to the same extent. These findings suggest that the hepatic disposition of LNS-50 at lower level should be ascribed to the less amount of serum opsonins associated on the surface and that the serum proteins associated with these spheres should be important as a determinant for their hepatic disposition.
KW - Hepatic uptake
KW - Opsonins
KW - Polystyrene nanosphere
KW - Receptor-mediated phagocytosis
KW - Serum proteins
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U2 - 10.1016/S0168-3659(02)00196-7
DO - 10.1016/S0168-3659(02)00196-7
M3 - Article
C2 - 12220841
AN - SCOPUS:0037130558
SN - 0168-3659
VL - 83
SP - 89
EP - 96
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 1
ER -