Inhibitory effect of magnetic Fe₃O₄ nanoparticles coloaded with homoharringtonine on human leukemia cells in vivo and in vitro

Meiyu Chen1 Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou;2 Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Collaborative Innovation Center of Hematology, Soochow University, Suzhou;3 Collaborative Innovation Center of Hematology, Soochow University, Suzhou

Fei Xiong4 State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing;5 Collaborative Innovation Center of Suzhou Nano Science and Technology, Suzhou, People’s Republic of China

Liang Ma1 Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou;2 Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Collaborative Innovation Center of Hematology, Soochow University, Suzhou;3 Collaborative Innovation Center of Hematology, Soochow University, Suzhou

Hong Yao1 Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou;2 Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Collaborative Innovation Center of Hematology, Soochow University, Suzhou;3 Collaborative Innovation Center of Hematology, Soochow University, Suzhou

Qinrong Wang1 Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou;2 Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Collaborative Innovation Center of Hematology, Soochow University, Suzhou;3 Collaborative Innovation Center of Hematology, Soochow University, Suzhou

Lijun Wen1 Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou;2 Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Collaborative Innovation Center of Hematology, Soochow University, Suzhou;3 Collaborative Innovation Center of Hematology, Soochow University, Suzhou

Qian Wang1 Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou;2 Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Collaborative Innovation Center of Hematology, Soochow University, Suzhou;3 Collaborative Innovation Center of Hematology, Soochow University, Suzhou

Ning Gu4 State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing;5 Collaborative Innovation Center of Suzhou Nano Science and Technology, Suzhou, People’s Republic of ChinaCorrespondence[email protected]

Suning Chen1 Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou;2 Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Collaborative Innovation Center of Hematology, Soochow University, Suzhou;3 Collaborative Innovation Center of Hematology, Soochow University, SuzhouCorrespondence[email protected]

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Abstract

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 mm³ versus 457±100 mm³, 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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Acknowledgments

This study was supported by National Basic Research Program 973 of China (No 2011CB933500), the Priority Academic Program Development of Jiangsu Higher Education Institutions, National Natural Science Foundation of China (No 81473160), the Basic Research Program of Jiangsu Province (Natural Science Foundation, No BK20151422), Fundamental Research Funds for the Central Universities (No 2242014R30013 and No 2242016K40033), and Jiangsu Province Natural Science Fund (BE2015639).

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The authors report no conflicts of interest in this work.

Inhibitory effect of magnetic Fe₃O₄ nanoparticles coloaded with homoharringtonine on human leukemia cells in vivo and in vitro

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Inhibitory effect of magnetic Fe₃O₄ nanoparticles coloaded with homoharringtonine on human leukemia cells in vivo and in vitro