靶向超声造影剂诱导肿瘤细胞凋亡的研究

Lauren J Jablonowski, Averie Palovcak, M. Wheatley
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引用次数: 0

摘要

本研究旨在开发一种基于聚合物的可注射平台,以实现生物活性纳米颗粒的微创靶向递送。研究表明,聚合物稳定的气体微泡在增强超声图像方面是有效的,特别是那些涉及癌症肿瘤的超声图像。这些造影剂可用于双重目的,当设计包括一个特定的配体缀合到表面用于靶向和药物封装在壳。利用这些技术对抗癌症的研究正在进行中。肿瘤坏死因子相关凋亡诱导配体(Tumor necrosis factor related apoptosis-inducing ligand, TRAIL)是一种蛋白质,它不仅与癌细胞上的细胞死亡受体(DR4和DR5)结合靶向,而且这种结合还能促进被靶向细胞的凋亡。健康细胞具有竞争结合的诱饵受体。我们的假设是,静脉注射TRAIL偶联微泡,当暴露在超声波(US)下时,会破裂形成纳米碎片(n-Sh),将TRAIL运输到癌细胞受体,在那里结合引发细胞凋亡。
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Induction of Apoptosis by Targeted Ultrasound Contrast Agents in Cancer Therapy
This research aims to develop an injectable polymer-based, platform to enable minimally-invasive targeted delivery of bioactive nano particles. Studies have shown polymer-stabilized gas microbubbles to be effective in enhancing an ultrasound image, especially those involving cancerous tumors. These contrast agents can serve a dual purpose when designed to include a specific ligand conjugated to the surface for targeting and a drug encapsulated in the shell. Research is underway to harness these techniques in the fight against cancer. Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) is a protein that not only binds to cell death receptors (DR4 and DR5) on cancerous cells for targeting, but this binding also promotes apoptosis in the targeted cell. Healthy cells have decoy receptors that compete for binding. Our hypothesis is that intravenously injected TRAIL-conjugated microbubbles, when exposed to ultrasound (US), will burst to form nanoshards (n-Sh) which will transport the TRAIL to cancer cell receptors, where binding initiates apoptosis.
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