期刊
INTERNATIONAL JOURNAL OF NANOMEDICINE
卷 11, 期 -, 页码 4413-4422出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S105543
关键词
leukemia; magnetic nanoparticles; magnetic Fe3O4 nanoparticles; HHT
资金
- National Basic Research Program 973 of China [2011CB933500]
- Priority Academic Program Development of Jiangsu Higher Education Institutions, National Natural Science Foundation of China [81473160]
- Basic Research Program of Jiangsu Province (Natural Science Foundation) [BK20151422]
- Fundamental Research Funds for the Central Universities [2242014R30013, 2242016K40033]
- Jiangsu Province Natural Science Fund [BE2015639]
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 Fe3O4 nanoparticles (MNP-Fe3O4) to improve the therapeutic effect of HHT and investigated its biological effects. Within a certain range of concentrations, the HHT-MNP-Fe3O4 showed a more enhanced inhibitory effect on the selected myeloid leukemia cell lines than HHT alone. Compared with HHT, HHT-MNP-Fe3O4 could induce more extensive apoptosis in leukemia cells, which also showed more pronounced cell arrests at G0/G1 phase. HHT-MNP-Fe3O4 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-Fe3O4 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-Fe3O4 than with the controls. These findings provide a more efficient delivery system for HHT in the treatment of hematological malignancy.
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