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

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

Zou, Mingyuan;Xu, Peilan;Wang, Li;Wang, Lanlan;Li, Tingting;Liu, Cong;Shi, Lei;Xie, Jun;Li, Wanyun;Wang, Shengyu;Wu, Guoqiu;Luo, Fanghong;Wu, Ting;Yan, Jianghua;
artificial cells, nanomedicine, and biotechnology 2020 Vol. 48 pp. 116-128
410
zou2020designartificial

Abstract

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/FeO). , 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. , 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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84114
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10.1080/21691401.2019.1699817
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