Antibody-directed metal-organic framework nanoparticles for targeted drug delivery.,Acta Biomaterialia

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Antibody-directed metal-organic framework nanoparticles for targeted drug delivery.
Acta Biomaterialia ( IF 9.4 ) Pub Date : 2019-12-13 , DOI: 10.1016/j.actbio.2019.12.012
Vladimir R Cherkasov ₁ , Elizaveta N Mochalova ₁ , Andrey V Babenyshev ₁ , Julian M Rozenberg ₂ , Ilya L Sokolov ₂ , Maxim P Nikitin ₃

Affiliation

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. STATEMENT OF SIGNIFICANCE: The unique combination of exceptional drug capacity and controlled release, biodegradability and low toxicity makes nanosized metal-organic frameworks (nMOFs) nearly ideal drug vehicles for various biomedical applications. Unfortunately, the prospective of nMOF applications for the targeted drug delivery is still unclear since only a few examples have been reported for nMOF cell targeting, exclusively for small ligands. In this work, we fill the important gap and demonstrate nanoagent that can specifically kill target cancer cells via drug delivery based on recognition of HER2/neu cell surface receptors by such universal and specific tool as antibodies. The proposed approach is universal and can be adapted for specific biomedical tasks using antibodies of any specificity and nMOFs of a various composition.

中文翻译：

靶向药物的抗体导向的金属有机骨架纳米颗粒。

纳米金属有机框架（nMOF）作为用于各种应用的高容量载体已显示出巨大的希望。对于生物医学，已经提出了许多nMOF，它们几乎可以运输任何分子药物，可以微调其有效载荷释放曲线等。然而，其在靶向药物递送中的应用前景仍然相对不清楚。到目前为止，只有少数作品报道了nMOF仅通过小配体（例如叶酸或RGD肽）靶向特定细胞。在这里，我们展示了以通用工具（例如抗体）功能化的nMOF在体外将靶向药物递送至特定癌细胞的可行性。我们展示ca。120 nm磁性核/ MOFs壳纳米剂装有阿霉素/柔红霉素，并通过亲水性碳水化合物界面与抗体偶联。我们表明，nMOFs的羧甲基-葡聚糖涂层可以使药物分子大量负载（最高15.7 mg / g），在生理介质中持续释放并保留抗体特异性。曲妥珠单抗指导的选择性靶向和HER2 / neu阳性乳腺癌细胞的体外杀伤说明了药剂的可靠性能。该方法扩展了nMOF的应用范围，可作为开发有效的治疗纳米剂的平台。意义声明：出色的药物容量和控释，生物降解性和低毒性的独特结合使纳米级金属有机框架（nMOF）几乎成为各种生物医学应用的理想药物载体。很遗憾，nMOF在靶向药物递送中的应用前景仍然不明确，因为只有少数几个例子报道了nMOF细胞靶向，仅针对小配体。在这项工作中，我们填补了重要的空白，并证明了纳米试剂可以通过药物递送特异性杀伤目标癌细胞，而这种纳米药物是通过对HER2 / neu细胞表面受体的识别，并通过诸如抗体之类的通用和特定工具来实现的。所提出的方法是通用的，并且可以使用任何特异性的抗体和各种组成的nMOF适应特定的生物医学任务。我们填补了重要的空白，并证明了纳米试剂可以通过药物递送特异性杀伤目标癌细胞，而这种纳米药物是通过这种通用和特异性工具（例如抗体）对HER2 / neu细胞表面受体的识别而实现的。所提出的方法是通用的，并且可以使用任何特异性的抗体和各种组成的nMOF适应特定的生物医学任务。我们填补了重要的空白，并展示了可以通过药物递送特异性杀伤目标癌细胞的纳米剂，该纳米剂基于对HER2 / neu细胞表面受体的识别，并通过诸如抗体之类的通用和特定工具进行。所提出的方法是通用的，并且可以使用任何特异性的抗体和各种组成的nMOF适应特定的生物医学任务。

更新日期：2019-12-13

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