Combination therapy comprising irreversible electroporation and hydroxycamptothecin loaded electrospun membranes to treat rabbit VX2 subcutaneous cancer
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Irreversible electroporation (IRE) is a kind of promising cancer treatment technology. However, local recurrence still occurs because of incomplete ablation. The aim of this study was to investigate the combined therapy of IRE and a hydroxycamptothecin loaded electrospun membrane (EM/HCPT) to treat rabbit VX2 subcutaneous cancer. HCPT loaded membranes were developed by electrospinning. Mechanical test and in vitro drug release study of EM/HCPT were performed. 24 rabbits with subcutaneous VX2 tumor were randomly divided into four groups: the control group, the EM/HCPT group, the IRE ablation group, and the IRE + EM/HCPT group. The tumor cells were ablated by IRE first, followed by subcutaneous implantation of EM/HCPT to release HCPT constantly in order to damage the residual cancer cells. The tumor inhibition efficacy was assessed by the tumor real-time monitoring, histological and immunofluorescent analyses, and transmission electron microscopy (TEM) examination. Assessment of the release from EM/HCPT showed that HCPT release lasted for about 7 days. The in vivo antitumor efficacy assessment, histological and immunofluorescent analyses, and TEM examination showed that IRE + EM/HCPT had the best tumor inhibition ability. In addition, the biochemical analyses and hematoxylin and eosin (H&E) staining of normal organs indicated that IRE + EM/HCPT treatment was safe. Our study provided a new concept in cancer treatment and might promote the application of IRE.
KeywordsIrreversible electroporation Hydroxycamptothecin Electrospun membrane VX2 cancer Combination therapy
We thank Elixigen Corporation (Huntington Beach, California, USA) for helping in proofreading and editing the English of final manuscript.
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Conflict of interest
The authors report no declarations of interest.
- M. Figini, X. Wang, T. Lyu, Z. Su, D. Procissi, V. Yaghmai, et al., Preclinical and clinical evaluation of the liver tumor irreversible electroporation by magnetic resonance imaging. Am. J. Transl. Res. 9(2), 580–590 (2017)Google Scholar
- G. Kourounis, P. Paul Tabet, D. Moris, A. Papalambros, E. Felekouras, F. Georgiades, et al., Irreversible electroporation (Nanoknife(R) treatment) in the field of hepatobiliary surgery: Current status and future perspectives. Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology 22(1), 141–149 (2017)Google Scholar
- Z. Liu, H. Li, Y. Fan, Y. Liu, S. Man, P. Yu, et al., Combination treatment with Rhizoma Paridis and Rhizoma Curcuma longa extracts and 10-hydroxycamptothecin enhances the antitumor effect in H22 tumor model by increasing the plasma concentration. Biomed. Pharmacother. 83, 627–634 (2016)CrossRefGoogle Scholar
- L. Qinglin, X. Wenxiu, Z. Like, Fangluo, C. Gang, H. Ping, A study on the anti-tumor mechanism of total flavonoids from radix tetrastigmae against additional cell line based on COX-2-mediated Wnt/beta-catenin signaling pathway, Oncotarget (2017).Google Scholar
- N. Saderi, M. Rajabi, B. Akbari, M. Firouzi, Z. Hassannejad, Fabrication and characterization of gold nanoparticle-doped electrospun PCL/chitosan nanofibrous scaffolds for nerve tissue engineering. J. Mater. Sci. Mater. Med. 29(9) (2018)Google Scholar
- H. Wang, J. Feng, G. Liu, B. Chen, Y. Jiang, Q. Xie, In vitro and in vivo anti-tumor efficacy of 10-hydroxycamptothecin polymorphic nanoparticle dispersions: shape- and polymorph-dependent cytotoxicity and delivery of 10-hydroxycamptothecin to cancer cells. Nanomed.: Nanotechnol., Biol. Med. 12(4), 881–891 (2016)CrossRefGoogle Scholar