Design and construction of a magnetic targeting pro-coagulant protein for embolic therapy of solid tumors. Issue 1 (1st January 2020)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Artificial cells, nanomedicine, and biotechnology. Volume 48:Issue 1(2020)
• Page Start: 116
• Page End: 128
• Publication Date: 2020-01-01
• Subjects: Embolic therapy -- iron oxide nano-particles -- drug delivery -- targeting -- Neuropilin-1; Artificial cells -- Periodicals; Nanotechnology -- Periodicals; Blood substitutes -- Periodicals; Tissue engineering -- Periodicals; Molecules -- Periodicals; Biotechnology -- Periodicals; 615.39
• DOI: 10.1080/21691401.2019.1699817
• Languages: English
• ISSNs: 2169-1401

Abstract

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/Fe3 O4 ). 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.