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 μg/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.