Artificial Cells, Nanomedicine, and Biotechnology (Jan 2020)

Design and construction of a magnetic targeting pro-coagulant protein for embolic therapy of solid tumors

  • Mingyuan Zou,
  • Peilan Xu,
  • Li Wang,
  • Lanlan Wang,
  • Tingting Li,
  • Cong Liu,
  • Lei Shi,
  • Jun Xie,
  • Wanyun Li,
  • Shengyu Wang,
  • Guoqiu Wu,
  • Fanghong Luo,
  • Ting Wu,
  • Jianghua Yan

DOI
https://doi.org/10.1080/21691401.2019.1699817
Journal volume & issue
Vol. 48, no. 1
pp. 116 – 128

Abstract

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In this study, we have designed a magnetic targeting pro-coagulant protein (MTPCP) for the embolic therapy of solid tumours. The MTPCP consists of a magnetic carrier and a pro-coagulant protein. The pro-coagulant protein used in this study is the fusion protein tTF-EG3287 which is not pro-coagulant when free in the blood circulation, but presents strong pro-coagulant ability once bound to the Neuropilin-1(NRP-1) that is highly expressed on tumour-associated vascular endothelial cells. And the magnetic carrier is O-Carboxymethyl chitosan-coated iron oxide nanoparticles (OCMC/Fe3O4). In vitro, we assessed the NRP-1 targeting ability of the MTPCP using confocal microscopy and flow cytometry, and evaluated the potential pro-coagulant activity of the MTPCP using the Spectozyme FXa assay. In vivo, the magnetic targeting ability of the MTPCP was detected using a living imaging system. At last, we assessed the anticancer activity of the MTPCP on HepG2 tumour bearing BALB/c nude mice models including subcutaneous transplantation and orthotopic transplantation. HepG2 tumour bearing mice models revealed that after intravenous administration of the MTPCP, thrombosis specifically occurs on tumour-associated blood vessels, and resulting in tumour growth retardation. No apparent side effects, such as thrombosis in other organs or other treatment-related toxicity, were observed during the treatment. Our data showed that the MTPCP may be a promising embolic agent for the embolic therapy of solid tumours.

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