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
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用于实体瘤栓塞治疗的磁性靶向促凝蛋白的设计和构建
DOI：
10.1080/21691401.2019.1699817
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发表时间：
2020-01
期刊：
影响因子：
--
通讯作者：
Jianghua Yan
中科院分区：
文献类型：
--
作者：
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
在这项研究中，我们设计了一种磁性靶向促凝蛋白（MTPCP）用于实体肿瘤的栓塞治疗。MTPCP由磁性载体和促凝蛋白组成。本研究使用的促凝蛋白是融合蛋白tTF-EG3287，该蛋白在血液循环中游离时不具有促凝作用，但与肿瘤相关血管内皮细胞上高表达的Neuropilin-1（NRP-1）结合后具有较强的促凝能力。磁性载体为o -羧甲基壳聚糖包覆氧化铁纳米颗粒（OCMC/Fe3O4）。在体外，我们使用共聚焦显微镜和流式细胞术评估了MTPCP的NRP-1靶向能力，并使用Spectozyme FXa检测评估了MTPCP的潜在促凝活性。在体内，使用活体成像系统检测MTPCP的磁靶向能力。最后，我们评估了MTPCP对HepG2荷瘤BALB/c裸鼠模型（包括皮下移植和原位移植）的抗癌活性。HepG2荷瘤小鼠模型显示，静脉给药MTPCP后，肿瘤相关血管特异性发生血栓形成，导致肿瘤生长迟缓。在治疗过程中未观察到其他器官血栓形成或其他治疗相关毒性等明显副作用。我们的数据表明，MTPCP可能是一种很有前途的栓塞剂，用于实体肿瘤的栓塞治疗。
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/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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构建针对肿瘤血管系统的 Neuropilin-1 的新型促凝血蛋白用于肿瘤栓塞治疗
影响因子：
4.5
作者：
Zou Mingyuan;Samiullah Malik;Xu Peilan;Wang Shengyu;He Jie;Wu Ting;Luo Fanghong;Yan Jianghua
通讯作者：
Yan Jianghua
影响因子：
8
作者：
Tse BWC;Volpert M;Ratther E;Stylianou N;Nouri M;McGowan K;Lehman ML;McPherson SJ;Roshan-Moniri M;Butler MS;Caradec J;Gregory-Evans CY;McGovern J;Das R;Takhar M;Erho N;Alshalafa M;Davicioni E;Schaeffer EM;Jenkins RB;Ross AE;Karnes RJ;Den RB;Fazli L;Gregory PA;Gleave ME;Williams ED;Rennie PS;Buttyan R;Gunter JH;Selth LA;Russell PJ;Nelson CC;Hollier BG
通讯作者：
Hollier BG
影响因子：
6.4
作者：
A. Latil;D. Vidaud;A. Valéri;G. Fournier;M. Vidaud;R. Lidereau;O. Cussenot;I. Biàche
通讯作者：
A. Latil;D. Vidaud;A. Valéri;G. Fournier;M. Vidaud;R. Lidereau;O. Cussenot;I. Biàche
影响因子：
2.1
作者：
A. Dusza;M. Wojtyniak;N. Nedelko;A. Ślawska-Waniewska;J. Greneche;C. A. Rodrigues;C. Burger;C. Stringari;A. Debrassi
通讯作者：
A. Dusza;M. Wojtyniak;N. Nedelko;A. Ślawska-Waniewska;J. Greneche;C. A. Rodrigues;C. Burger;C. Stringari;A. Debrassi
影响因子：
4.8
作者：
Jia, HY;Bagherzadeh, A;Zachary, IC
通讯作者：
Zachary, IC