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设计抗体功能化的碳纳米管填充放射性金属以实现靶向抗癌治疗。

Design of antibody-functionalized carbon nanotubes filled with radioactivable metals towards a targeted anticancer therapy.

机构信息

CNRS, Institut de Biologie Moléculaire et Cellulaire, Laboratoire d'Immunopathologie et Chimie Thérapeutique, 67000 Strasbourg, France.

出版信息

Nanoscale. 2016 Jul 7;8(25):12626-38. doi: 10.1039/c5nr07923c. Epub 2016 Jan 6.

Abstract

In the present work we have devised the synthesis of a novel promising carbon nanotube carrier for the targeted delivery of radioactivity, through a combination of endohedral and exohedral functionalization. Steam-purified single-walled carbon nanotubes (SWCNTs) have been initially filled with radioactive analogues (i.e. metal halides) and sealed by high temperature treatment, affording closed-ended CNTs with the filling material confined in the inner cavity. The external functionalization of these filled CNTs was then achieved by nitrene cycloaddition and followed by the derivatization with a monoclonal antibody (Cetuximab) targeting the epidermal growth factor receptor (EGFR), overexpressed by several cancer cells. The targeting efficiency of the so-obtained conjugate was evaluated by immunostaining with a secondary antibody and by incubation of the CNTs with EGFR positive cells (U87-EGFR+), followed by flow cytometry, confocal microscopy or elemental analyses. We demonstrated that our filled and functionalized CNTs can internalize more efficiently in EGFR positive cancer cells.

摘要

在本工作中,我们设计了一种新颖的、有前途的碳纳米管载体,通过内笼和外笼功能化的结合,实现放射性物质的靶向递送。经过蒸汽提纯的单壁碳纳米管(SWCNTs)首先被放射性类似物(即金属卤化物)填充,并通过高温处理密封,得到填充材料被限制在内腔中的封闭端 CNTs。然后通过氮宾环加成反应对这些填充的 CNTs 进行外部功能化,随后用针对表皮生长因子受体(EGFR)的单克隆抗体(西妥昔单抗)进行衍生化,EGFR 在多种癌细胞中过表达。通过用二级抗体进行免疫染色以及将 CNTs 与 EGFR 阳性细胞(U87-EGFR+)孵育,然后进行流式细胞术、共聚焦显微镜或元素分析,评估所得到的缀合物的靶向效率。我们证明,我们的填充和功能化的 CNTs 可以更有效地内化到 EGFR 阳性癌细胞中。

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