Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, USA.
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia 30332, USA.
Nat Commun. 2017 Jun 8;8:15594. doi: 10.1038/ncomms15594.
The vascular endothelium presents a major transport barrier to drug delivery by only allowing selective extravasation of solutes and small molecules. Therefore, enhancing drug transport across the endothelial barrier has to rely on leaky vessels arising from disease states such as pathological angiogenesis and inflammatory response. Here we show that the permeability of vascular endothelium can be increased using an external magnetic field to temporarily disrupt endothelial adherens junctions through internalized iron oxide nanoparticles, activating the paracellular transport pathway and facilitating the local extravasation of circulating substances. This approach provides a physically controlled drug delivery method harnessing the biology of endothelial adherens junction and opens a new avenue for drug delivery in a broad range of biomedical research and therapeutic applications.
血管内皮细胞对药物输送构成了主要的传输屏障,仅允许溶质和小分子的选择性渗出。因此,要想增强药物穿过内皮屏障的输送,就必须依赖于由病理血管生成和炎症反应等疾病状态引起的渗漏血管。在这里,我们展示了可以利用外部磁场通过内化的氧化铁纳米颗粒暂时破坏内皮细胞紧密连接,从而增加血管内皮的通透性,激活细胞旁转运途径,并促进循环物质的局部渗出。这种方法提供了一种物理控制的药物输送方法,利用了内皮细胞紧密连接的生物学特性,为广泛的生物医学研究和治疗应用中的药物输送开辟了新途径。
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