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Preparation and labeling of surface-modified magnetoferritin protein cages with a rhenium(I) carbonyl complex for magnetically targeted radiotherapy

机译:用铼(I)羰基复合物进行表面改性磁铁蛋白蛋白笼的制备及标记磁靶向放射疗法

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摘要

New rhenium radiolabeled compounds are of general interest due to their nuclear characteristics which allow radiotherapy and in situ monitoring of tumor uptake. Biocompatible magnetic nanoparticles capable of transporting radionuclides, providing MRI contrast agent properties for imaging and a therapeutic effect in the target tissue simultaneously, are highly desirable. Herein we describe the preparation of magnetoferritin samples, and their labeling with rhenium in the form of the low oxidation state rhenium(I)-tricarbonyl complex, [Re(CO)(3)(H2O)(3)](+). A non-radioactive rhenium isotope (Re-187) was used in all studies. The rhenium complex was conjugated covalently to the surface lysine groups of the protein cage via glutaraldehyde crosslinker and histidine modification. The analyses of conjugates were performed by inductively coupled plasma mass spectroscopy (ICP-MS) and size exclusion chromatography (SEC). Labeling efficiency was calculated as 22 +/- 2 rhenium per protein cage. The in vitro stability of the rhenium carbonyl label was evaluated at room temperature and in human serum medium. It was found that 91.1 +/- 1.8% rhenium was retained on the surface of the magnetoferritin cage following 72 h of dialysis. Prussian blue staining revealed the uptake of rhenium labeled nanocages preferentially into the human breast metastatic adenocarcinoma, MDA-MB-231 cells lines. The cytotoxicity assay carried out with the same cell lines showed that there is no significant cytotoxic effect up to 72 hours of incubation with 1 mg of labeled nanocages per mL (IC50 value).
机译:由于它们的核特性,新的铼放射性标记化合物具有一般性兴趣,这允许放疗和原位监测肿瘤摄取。能够输送放射性核素的生物相容性磁性纳米颗粒,提供MRI造影剂的成像和同时在靶组织中的治疗效果,是非常理想的。在此,我们描述了磁铁脲素样品的制备,以及它们以低氧化态铼(I) - 三羰基复合物形式的铼的标记,[Re(CO)(3)(3)(H 2 O)(3)](+)。在所有研究中使用非放射性铼同位素(RE-187)。通过戊二醛交联剂和组氨酸改性将铼络合物与蛋白质笼的表面赖氨酸基团共轭。通过电感耦合等离子体质谱(ICP-MS)和尺寸排阻色谱(SEC)进行缀合物的分析。标记效率计算为每种蛋白质笼子22 +/- 2铼。在室温和人血清培养基中评价碳基标记的体外稳定性。发现在72小时后保留91.1 +/- 1.8%铼在透析后72小时后保留在磁铁烧烤蛋白笼的表面上。普鲁士蓝染色揭示了优先进入人乳腺转移性腺癌,MDA-MB-231细胞系中的铼标记的纳米病的吸收。用相同细胞系进行的细胞毒性测定表明,没有显着的细胞毒性效果,高达72小时的孵育,每mL(IC 50值)与1mg标记的纳米病孵育。

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  • 来源
    《RSC Advances》 |2016年第11期|共10页
  • 作者单位

    Middle E Tech Univ Dept Chem TR-06800 Ankara Turkey;

    Middle E Tech Univ Dept Biotechnol TR-06800 Ankara Turkey;

    Middle E Tech Univ Dept Chem TR-06800 Ankara Turkey;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
  • 关键词

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