Inhibitory effect of magnetic FeO nanoparticles coloaded with homoharringtonine on human leukemia cells in vivo and in vitro.

Homoharringtonine (HHT), a natural cephalotaxine alkaloid, has been used in the People's Republic of China for treatment of leukemia for >3 decades. Here, we employed magnetic FeO nanoparticles (MNP-FeO) to improve the therapeutic effect of HHT and investigated its biological effects. Within a certain range of concentrations, the HHT-MNP-FeO showed a more enhanced inhibitory effect on the selected myeloid leukemia cell lines than HHT alone. Compared with HHT, HHT-MNP-FeO could induce more extensive apoptosis in leukemia cells, which also showed more pronounced cell arrests at G0/G1 phase. HHT-MNP-FeO enhanced antitumor activity by downregulating myeloid cell leukemia-1, which could inhibit the activation of caspase-3 and poly-ADP-ribose polymerase. In vivo experiments using tumor-bearing animal models showed that the mean tumor volume with HHT-MNP-FeO was significantly smaller than that with HHT alone (193±26 mm versus 457±100 mm, <0.05), while the mean weight was 0.67±0.03 g versus 1.42±0.56 g (<0.05). Immunohistochemical study showed fewer myeloid cell leukemia-1-stained cells in mice treated with HHT-MNP-FeO than with the controls. These findings provide a more efficient delivery system for HHT in the treatment of hematological malignancy.