Asialoglycoprotein receptor-targeted superparamagnetic iron oxide nanoparticles.
Superparamagnetic iron oxide (SPIO) nanoparticles are primarily used as contrast agents in magnetic resonance imaging. SPIO have also been derivatized to add targeting and drug-carrier functionality as drug delivery devices. The preparation and characterization of amino-functionalized SPIO (ASPIO) and lactose-derivatized galactose-terminal-ASPIO are now reported. The target for galactose-terminal-ASPIO is the cell-surface asialoglycoprotein receptor (ASGPR) expressed by hepatocytes. Two batches of ASPIO with average particle sizes of 61 [42]nm and 127 [125]nm [full-width half maximum; FWHM] were prepared. The small ASPIO increased from 61 nm to 278 [309]nm upon lactosylation (Gal-ASPIO-278) and to 302 [280] by N-acetylation (NAcASPIO-302); the larger ASPIO afforded galactosyl-terminal ASPIO of 337 [372]nm and N-acetylated ASPIO of 326 [308]nm. The LD50 of Gal-ASPIO-278 was 1500 microg/mL to HepG2 cells; Gal-ASPIO-278 associated with HepG2 cells in vitro, whereas NAcSPIO-302, prepared from the same ASPIO batch, did not. Gal-ASPIO-278 and NAcASPIO-302 were not bound by ASPGR non-expressing 143B cells. The association of Gal-ASPIO-278 to HepG2 cells was reduced by free galactose, supporting the model of ASGPR-mediated binding. These data underline the potential application of Gal-ASPIO as a targeted ligand for ASPGR-expressing cells in vivo.
Faculty of Pharmacy and Pharmaceutical Sciences, Edmonton, Canada.
Guifang
G
Huang
James
J
Diakur
Zhenghe
Z
Xu
Leonard I
LI
Wiebe
D000107:Acetylation; D037263:Asialoglycoprotein Receptor / Q000187:drug effects*; D002460:Cell Line; D045744:Cell Line, Tumor; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D005290:Ferric Compounds / Q000008:administration & dosage / Q000737:chemistry*; D005690:Galactose / Q000737:chemistry; D022781:Hepatocytes / Q000502:physiology; D006801:Humans; D007785:Lactose / Q000737:chemistry; D008027:Light; D008107:Liver Diseases / Q000175:diagnosis; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008280:Magnetics; D053758:Nanoparticles; D010316:Particle Size; D012542:Scattering, Radiation
D037263:Asialoglycoprotein Receptor; D005290:Ferric Compounds; C000499:ferric oxide; D007785:Lactose; D005690:Galactose