The cellular transmembrane receptor Neuropilin-1(NRP-1) is overexpressed in tumour tissue and endothelial cells of tumour vessels, whereas it has limited expression in normal tissues. This study aimed to design a novel recombinant protein tTF-EG3287, which consisting of the truncated tissue factor (tTF) and the NRP-1 targeting peptide EG3287. The procoagulant protein selectively activates blood coagulation in tumour vessels once bound to the cell surface of the tumour vasculature by a targeting peptide EG3287. In this study, procoagulant activity of the recombinant protein tTF-EG3287 was evaluated by Spectozyme FXa assay. NRP-1 targeting ability was analysed by fluorescence confocal microscopy and flow cytometry. The living imaging system was used to assess the tumour targeting ability of recombinant proteins tTF-EG3287 in vivo. Tumour growth inhibition showed effective antitumor activity in HepG2 tumour-bearing nude mice. Histological study showed obvious thrombosis and thromboembolism in tumour vessels and cell necrosis of tumour tissue, without any clear side effect such as thrombosis in other organs.
Keywords: Tumor vascular targeting; neuropilin-1; procoagulant protein; tumour embolisation therapy.