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Combination therapy comprising irreversible electroporation and hydroxycamptothecin loaded electrospun membranes to treat rabbit VX2 subcutaneous cancer

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Abstract

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.

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References

  • U. Aggarwal, A.K. Goyal, G. Rath, Development and characterization of the cisplatin loaded nanofibers for the treatment of cervical cancer. Mater. Sci. Eng. C Mater. Biol. Appl. 75, 125–132 (2017)

    Article  Google Scholar 

  • R. Cannon, S. Ellis, D. Hayes, G. Narayanan, R.C. Martin 2nd, Safety and early efficacy of irreversible electroporation for hepatic tumors in proximity to vital structures. Eur. J. Surg. Oncol. 107(5), 544–549 (2013)

    Article  Google Scholar 

  • W. Cui, X. Li, X. Zhu, G. Yu, S. Zhou, J. Weng, Investigation of drug release and matrix degradation of electrospun poly(DL-lactide) fibers with paracetanol inoculation. Biomacromolecules 7(5), 1623–1629 (2006)

    Article  Google Scholar 

  • 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 

  • Y. Guo, Y. Zhao, T. Wang, R. Li, M. Han, Z. Dong, et al., Hydroxycamptothecin Nanorods Prepared by Fluorescently Labeled Oligoethylene Glycols (OEG) Codendrimer: Antitumor Efficacy in Vitro and in Vivo. Bioconjug. Chem. 28(2), 390–399 (2017)

    Article  Google Scholar 

  • H. Jiang, Y. Hu, Y. Li, P. Zhao, K. Zhu, W. Chen, A facile technique to prepare biodegradable coaxial electrospun nanofibers for controlled release of bioactive agents. J. Control. Release 108(2–3), 237–243 (2005)

    Article  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 

  • E.W. Lee, C. Chen, V.E. Prieto, S.M. Dry, C.T. Loh, S.T. Kee, Advanced hepatic ablation technique for creating complete cell death: irreversible electroporation. Radiology 255(2), 426–433 (2010)

    Article  Google Scholar 

  • J. Li, Z. Sun, J. Zhang, H. Shao, M.M. Cona, H. Wang, et al., A dual-targeting anticancer approach: soil and seed principle. Radiology 260(3), 799–807 (2011)

    Article  Google Scholar 

  • J.N. Li, W.G. Xu, J.J. Chen, D. Li, K. Zhang, T.J. Liu, et al., Highly Bioadhesive Polymer Membrane Continuously Releases Cytostatic and Anti-Inflammatory Drugs for Peritoneal Adhesion Prevention. ACS Biomater Sci. Eng. 4(6), 2026–2036 (2018)

    Article  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)

    Article  Google Scholar 

  • R.C. Martin 2nd, D. Kwon, S. Chalikonda, M. Sellers, E. Kotz, C. Scoggins, et al., Treatment of 200 locally advanced (stage III) pancreatic adenocarcinoma patients with irreversible electroporation: safety and efficacy. Ann. Surg. 262(3), 486–494 (2015) discussion 492–4

    Article  Google 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).

  • 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)

  • O.F. Sarioglu, A. Ozdemir, K. Karaboduk, T. Tekinay, Comparative serum albumin interactions and antitumor effects of Au(III) and Ga(III) ions. J. Trace Elem. Med. Biol. 29, 111–115 (2015)

    Article  Google Scholar 

  • S.V. Sudakaran, J.R. Venugopal, G.P. Vijayakumar, S. Abisegapriyan, A.N. Grace, S. Ramakrishna, Sequel of MgO nanoparticles in PLACL nanofibers for anti-cancer therapy in synergy with curcumin/beta-cyclodextrin. Mater. Sci. Eng. C Mater. Biol. Appl. 71, 620–628 (2017)

    Article  Google Scholar 

  • J.A. Vogel, E. van Veldhuisen, P. Agnass, J. Crezee, F. Dijk, J. Verheij, et al., Time-Dependent Impact of Irreversible Electroporation on Pancreas, Liver, Blood Vessels and Nerves: A Systematic Review of Experimental Studies. PloS one 11(11), e0166987 (2016)

    Article  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)

    Article  Google Scholar 

  • J.J. Wendler, R. Ganzer, B. Hadaschik, A. Blana, T. Henkel, K.U. Kohrmann, et al., Irreversible electroporation. Current value for focal treatment of prostate cancer. Der Urologe. Ausg. A 54(6), 854–862 (2015)

    Article  Google Scholar 

  • C. Zhang, D. Pan, K. Luo, W. She, C. Guo, Y. Yang, et al., Peptide dendrimer-Doxorubicin conjugate-based nanoparticles as an enzyme-responsive drug delivery system for cancer therapy. Adv. Healthc. Mater. 3(8), 1299–1308 (2014)

    Article  Google Scholar 

  • M. Zhu, X.A. Lin, X.M. Zha, W.B. Zhou, T.S. Xia, S. Wang, Evaluation of the therapeutic efficacy of sequential therapy involving percutaneous microwave ablation in combination with 131I-hypericin using the VX2 rabbit breast solid tumor model. PloS one 10(3), e0120303 (2015)

    Article  Google Scholar 

  • A. Zimmerman, D. Grand, K.P. Charpentier, Irreversible electroporation of hepatocellular carcinoma: patient selection and perspectives. Journal of Hepatocellular Carcinoma 4, 49–58 (2017)

    Article  Google Scholar 

Download references

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We thank Elixigen Corporation (Huntington Beach, California, USA) for helping in proofreading and editing the English of final manuscript.

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Correspondence to Yaqin Qu or Renna Qiu.

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Wang, L., Chang, J., Qu, Y. et al. Combination therapy comprising irreversible electroporation and hydroxycamptothecin loaded electrospun membranes to treat rabbit VX2 subcutaneous cancer. Biomed Microdevices 20, 88 (2018). https://doi.org/10.1007/s10544-018-0336-y

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