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

Autor: 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
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Artificial Cells, Nanomedicine, and Biotechnology, Vol 48, Iss 1, Pp 116-128 (2020)
Druh dokumentu: article
ISSN: 21691401
2169-141X
2169-1401
DOI: 10.1080/21691401.2019.1699817
Popis: 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.
Databáze: Directory of Open Access Journals
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