Asialoglycoprotein receptor-targeted superparamagnetic iron oxide nanoparticles

Abstract

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.