Inhibitory effect of magnetic Fe(3)O(4) 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 Fe(3)O(4) nanoparticles (MNP-Fe(3)O(4)) to improve the therapeutic effect of HHT and investigated its biological effects. Within a certain range of concentrations, the HHT-MNP-Fe(3)O(4) showed a more enhanced inhibitory effect on the selected myeloid leukemia cell lines than HHT alone. Compared with HHT, HHT-MNP-Fe(3)O(4) could induce more extensive apoptosis in leukemia cells, which also showed more pronounced cell arrests at G0/G1 phase. HHT-MNP-Fe(3)O(4) 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-Fe(3)O(4) was significantly smaller than that with HHT alone (193±26 mm(3) versus 457±100 mm(3), P<0.05), while the mean weight was 0.67±0.03 g versus 1.42±0.56 g (P<0.05). Immunohistochemical study showed fewer myeloid cell leukemia-1-stained cells in mice treated with HHT-MNP-Fe(3)O(4) than with the controls. These findings provide a more efficient delivery system for HHT in the treatment of hematological malignancy.