Synthesis of iron oxide nanocrystals functionalized with hyaluronic acid and 131I-cetuximab for targeted combined (radio-photothermal) treatment of HepG2 cells.

Surface coating of NIR-plasmonic iron oxide magnetic nanocrystals (Fe3O4 MNCs) with natural polysaccharides is a promising strategy for increasing their uptake by cancer cells. In this work, chitosan-coated magnetic nanocrystals (Fe3O4@CS MNCs) were prepared and subsequently chemically conjugated with hyaluronic acid (HA). The cellular uptake of MNCs post treatment of HepG2 cells with the synthesized (Fe3O4@CS MNCs) and (Fe3O4@CS-HA MNCs) was 18.1 ± 0.8 and 25.2 ± 1.3 μg Fe/mL, respectively. The enhancement of MNCs cellular uptake is attributed to HA targeting of the cluster of differentiation 44 (CD44) protein extracellularly expressed on HepG2 cells. In another model, HA was covalently attached to the monoclonal antibody cetuximab. The produced (Fe3O4@CS-HA-Cet MNCs) showed the highest cellular uptake (31.4 ± 1.9 μg Fe/mL) via selective binding to the epidermal growth factor receptor (EGFR) overexpressed in HepG2 cells. Consequently, the phototoxicity against HepG2 cells upon near-infrared (NIR) laser light (808 nm, 1.5 W/cm2) at different concentrations of Fe follows the order: (Fe3O4@CS-HA-Cet MNCs) > (Fe3O4@CS-HA MNCs) > (Fe3O4@CS MNCs). For enhancement of the therapeutic efficiency, a combined targeted radio-photothermal candidate was synthesized by radiolabeling the antibody with Iodine-131. The combinatorial model (Fe3O4@CS-HA-Cet-131I MNCs) exhibited the highest toxicity against HepG2 cells upon NIR irradiation due to the synergistic combined radio- photothermal action.