A novel melittin nano-liposome exerted excellent anti-hepatocellular carcinoma efficacy with better biological safety
- Jie Mao†1,
- Shujun Liu†1,
- Min Ai†2,
- Zhuo Wang3,
- Duowei Wang1,
- Xianjing Li1,
- Kaiyong Hu1,
- Xinghua Gao1, 4Email author and
- Yong Yang1, 4Email author
© The Author(s). 2017
Received: 11 February 2017
Accepted: 14 March 2017
Published: 20 March 2017
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.
KeywordsBee venom Melittin nano-liposomes Anti-tumor activity Biological safety
Letter to the editor
Melittin is the main effective component of bee venom and has extensive biological functions in vivo, including anti-cancer property. To evaluate the anti-cancer activity of melittin on hepatocellular carcinoma (HCC), a clinical trial containing 40 HCC patients was conducted in Yancheng Second People’s Hospital (Yancheng, China). Patients with melittin treatment showed partial remission (PR) (n = 4, 10%), stable disease (SD) (n = 24, 60%), and progressive disease (PD) (n = 12, 30%), and the disease control rate (CR + PR + SD) was 70%. Toxicity was also assessable in the 40 patients. The most common adverse events were pain at the administration site and skin itch, which disappeared after melittin withdrawal (32 grade 0, 6 grade I, and 2 grade II). This results together with other preclinical studies of melittin indicated that it exerted a significant anti-HCC activity, while serious side effects have restricted the clinical application of melittin in cancer therapy [1–4]. To resolve these problems, melittin was modified with 2% poloxamer 188 and melittin nano-liposomes were prepared (Patent number: CN 101391098 A).
In summary, our results revealed that melittin significantly delayed HCC development with certain side effects in clinic trial. Novel melittin nano-liposomes showed outstanding anti-HCC potency in vitro and in vivo with a decreased toxicity. The results potentially have clinical implications for melittin nano-liposomes as a promising new drug for HCC therapy.
This work was supported by the National Science Foundation of China (Nos. 81673468, 91529304, 81473230, and 81403020), “Major Drug Discovery” science and technology major projects of China (No. 2011ZX09102-001-20), the 111 Project (No. 111-2-07), and Foundation of Nanjing University of Chinese Medicine (13XZR19).
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LSJ, MJ, and AM initiated and designed the in vitro and in vivo studies. WDW and HKY performed the preclinical animal studies. LXJ performed the in vitro experiments. FJH, GXH, and YY conceived the study, participated in its design and coordination, and helped to draft the manuscript. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
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Ethics approval and consent to participate
All animals were obtained from SLRC Laboratory Animal Co. Ltd. (Shanghai, China). Mice were bred, treated, and maintained under specific pathogen-free conditions at 24 ± 1 °C and 55 ± 5% humidity in a barrier facility with 12-h light-dark cycles. All animal experiments were performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals, with the approval of center for new drug evaluation and research, China Pharmaceutical University (Nanjing, China).
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