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首页> 外文期刊>Acta biomaterialia >Antibody-directed metal-organic framework nanoparticles for targeted drug delivery
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Antibody-directed metal-organic framework nanoparticles for targeted drug delivery

机译：针对靶向药物递送的抗体导向金属 - 有机骨架纳米粒子

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Nanosized metal-organic frameworks (nMOFs) have shown great promise as high-capacity carriers for a variety of applications. For biomedicine, numerous nMOFs have been proposed that can transport virtually any molecular drug, can finely tune their payload release profile, etc. However, perspectives of their applications for the targeted drug delivery remain relatively unclear. So far, only a few works have reported specific cell targeting by nMOFs exclusively through small ligands such as folic acid or RGD peptides. Here we show feasibility of targeted drug delivery to specific cancer cells in vitro with nMOFs functionalized with such universal tool as an antibody. We demonstrate ca. 120 nm magnetic core/MOFs shell nanoagents loaded with doxorubicin/daunorubicin and coupled with an antibody though a hydrophilic carbohydrate interface. We show that carboxymethyl-dextran coating of nMOFs allows extensive loading of the drug molecules (up to 15.7 mg/g), offers their sustained release in physiological media and preserves antibody specificity. Reliable performance of the agents is illustrated with trastuzumab-guided selective targeting and killing of HER2/neu-positive breast cancer cells in vitro. The approach expands the scope of nMOF applications and can serve as a platform for the development of potent theranostic nanoagents.
机译：纳米化金属 - 有机框架（NMOFS）已经表现为适用于各种应用的高容量载体。对于生物医用，已经提出了许多NMOF，其可以通过几乎任何分子药物运输，可以精细地调节其有效载荷释放型材等。然而，它们对靶向药物递送的应用的观点仍然尚不清楚。到目前为止，只有少数作业报告了NMOF的特异性细胞，仅通过小配体，例如叶酸或RGD肽。在这里，我们将靶向药物输送到特异性癌细胞的可行性在体外用与抗体这样的通用工具官能化的NMOF。我们展示了CA. 120nm磁芯/ mofs壳纳米烷基纳代纳蛋白含有多柔比蛋白/ daUnorubi in，并与亲水性碳水化合物界面偶联。我们表明NMOFS的羧甲基 - 葡聚糖涂层允许广泛负载药物分子（高达15.7mg / g），在生理介质中提供持续释放，并保留抗体特异性。具有可靠的代理的性能，并在体外用曲据引导的选择性靶向和杀死Her2 / Neu-阳性乳腺癌细胞的靶向靶向和杀伤。该方法扩展了NMOF应用的范围，并可以作为开发有效的Theranostic Nanagents的平台。

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