Non-ionic surfactant vesicles simultaneously enhance antitumor activity and reduce the toxicity of cantharidin
Wei Han,1,* Shengpeng Wang,2,* Rixin Liang,1 Lan Wang,1 Meiwan Chen,2 Hui Li,1 Yitao Wang1,2
1Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China
*These authors contributed equally to this work
Objective: The objective of the present study was to prepare cantharidin-entrapped non-ionic surfactant vesicles (CTD-NSVs) and evaluate their potential in enhancing the antitumor activities and reducing CTD’s toxicity.
Methods and results: CTD-NSVs were prepared by injection method. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry analysis showed that CTD-NSVs could significantly enhance in vitro toxicity against human breast cancer cell line MCF-7 and induce more significant cell-cycle arrest in G0/G1 phase. Moreover, Hoechst 33342 staining implicated that CTD-NSVs induced higher apoptotic rates in MCF-7 cells than free CTD solution. In vivo therapeutic efficacy was investigated in imprinting control region mice bearing mouse sarcoma S180. Mice treated with 1.0 mg/kg CTD-NSVs showed the most powerful antitumor activity, with an inhibition rate of 52.76%, which was significantly higher than that of cyclophosphamide (35 mg/kg, 40.23%) and the same concentration of free CTD (1.0 mg/kg, 31.05%). In addition, the acute toxicity and liver toxicity of CTD were also distinctly decreased via encapsulating into NSVs.
Conclusion: Our results revealed that NSVs could be a promising delivery system for enhancing the antitumor activity and simultaneously reducing the toxicity of CTD.
Keywords: cantharidin, non-ionic surfactant vesicle, toxicity, antitumor activity
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