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01.12.2017 | Letter to the Editor | Ausgabe 1/2017 Open Access

Journal of Hematology & Oncology 1/2017

A novel melittin nano-liposome exerted excellent anti-hepatocellular carcinoma efficacy with better biological safety

Journal of Hematology & Oncology > Ausgabe 1/2017
Jie Mao, Shujun Liu, Min Ai, Zhuo Wang, Duowei Wang, Xianjing Li, Kaiyong Hu, Xinghua Gao, Yong Yang
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s13045-017-0442-y) contains supplementary material, which is available to authorized users.


Melittin is the main effective component of bee venom and has extensive biological functions; however, serious side effects have restricted its clinical application. Preclinical and clinical studies showed that the main adverse events were allergic reaction and pain at the administration site. To decrease the toxicity, we prepared melittin nano-liposomes by encapsulating melittin with poloxamer 188 and explored the inhibitory activities on liver cancer together with biological safety. Here, we showed that melittin nano-liposomes significantly inhibited the survival of hepatocellular carcinoma (HCC) cells in vitro and prominently suppressed the growth of subcutaneous and orthotopic HCC transplantation tumors in vivo. It was important that it induced less inflammation and allergy in mice compared with melittin. Overall, melittin nano-liposomes would have a better application in HCC therapy due to its significant anti-tumor activity and better biological safety.

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Additional file 1: Materials and methods. (DOCX 24 kb)
Additional file 2: Figure S1. The effects of melittin nano-liposomes on the proliferation and apoptosis of tumor cells. (a) Proliferation inhibiting rates of melittin and melittin nano-liposomes on various HCC cells lines including LM-3, Bel-7402, SMMC-7721, HepG2, and L02 cells. (b) Cell nucleus staining by DAPI to observe the apoptosis of Bel-7402 and SMMC-7721 cells after treated with vehicle, blank liposomes (1 μM), melittin (1 μM), or melittin nano-liposomes (1 μM) for 24 h. (c) Fluorescence staining of Annexin V-FITC and PI to detect the apoptosis of HepG2 cells after treatment with melittin and Melittin nano-liposomes for 24 h and observed by fluorescence microscope. HepG2 cells were pretreated with Z-VAD-FMK for 6 hours, and melittin and Melittin nano-liposomes were subsequently administered at a concentration of 2 μM. (PDF 848 kb)
Additional file 3: Figure S2. Photo of HepG2 tumors of vehicle, blank liposomes (8 mg/kg), melittin (2 mg/kg), melittin nano-liposomes (2, 4, and 8 mg/kg), and sorafenib (30 mg/kg) treated groups in the HepG2 subcutaneous transplanted tumor model. The data are presented as the mean ± SEM. Statistical significance was calculated using Student’s t test (**p ≤ 0.01; ***p ≤ 0.001). (PDF 1070 kb)
Additional file 4: Figure S3. Flow cytometry analysis of splenic immune cells including splenic T lymphocytes, neutrophil and B lymphocytes. Spleens were stripped and grinded into cell suspension after mice were treated with vehicle, blank liposomes (8 mg/kg), melittin (2 mg/kg) and melittin nano-liposomes (2 mg/kg) for two weeks. (PDF 730 kb)
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