Sci Adv:程柯团队带来抗体药物靶向受损心脏新方法

2020-02-07 不详 生物探索

来自北卡罗莱纳州立大学和北卡大学教堂山分校的一项研究报道了一种新型血小板微粒,可以实现将抗炎抗体药物靶向运输到缺血损伤心脏的效果。目前这项研究以封面文章的形式发表在《Science Advances》杂志上。程柯教授是文章的通讯作者,博士后研究员李振华博士为本文的第一作者。

来自北卡罗莱纳州立大学和北卡大学教堂山分校的一项研究报道了一种新型血小板微粒,可以实现将抗炎抗体药物靶向运输到缺血损伤心脏的效果。目前这项研究以封面文章的形式发表在《Science Advances》杂志上。程柯教授是文章的通讯作者,博士后研究员李振华博士为本文的第一作者。


https://advances.sciencemag.org/content/6/6/eaay0589

血管疾病被认为与炎症密切相关,白介素-1β(IL-1β)是炎症信号通路的关键分子。该蛋白诱导炎症反应,并随着时间的推移促进心脏瘢痕组织的形成,恶化心脏功能。目前针对IL-1β所开发的抗体药物(如Canakinumab ,商品名Ilaris) 已完成III期临床试验。临床研究表明,Canakinumab可以明显降低部分心肌梗死患者的主要心血管不良事件发生率,为抗炎心血管疾病治疗提供了强有力的证据支持。

“IL-1β虽然在这个过程起负面作用,但它也是身体抵御外界病原体的防御机制之一。它通过引发炎症来摧毁入侵者。” 北卡州立大学Randall B. Terry Jr.再生医学杰出教授、北卡州立大学/北卡大学教堂山分校生物医学工程系程柯教授介绍说。

“因此,静脉注射周身给药的这种方式,会在全身无差别阻碍IL-1β的功能,可能会带来一些副作用。因此我们希望能开发一种方法,将该药物靶向运送到心脏,从而降低周身反应。”

具有天然的“归巢”能力的血小板(一种促进血液凝固的微小血细胞),能够靶向心脏损伤。程柯教授课题组前期的工作已经证明,血小板膜修饰的干细胞和纳米颗粒,具有靶向受损心脏的能力。(详见生物探索对程柯教授的专访及其相关工作的报道)。

在这项最新的研究中,研究小组制备了血小板微粒,并在其表面插入IL-1β阻断抗体,构建了这种新型心梗靶向性抗炎药物。研究发现,接受靶向药物治疗的小鼠心脏中药物分布比非靶向治疗的小鼠高约10倍。70天后,接受靶向药物治疗的小鼠心功能得到了更好的恢复。


抗IL-1β单抗修饰的血小板微粒用于心脏靶向抗炎和修复

“血小板能有效地将药物直接运送到受损器官,使得靶器官具有更高的药物浓度。”程柯教授说。这种新型的损伤特异性抗体靶向药物能潜在实现药物针对靶器官的精准、有效递送,为心血管疾病的精准抗炎治疗提供新的策略。

原始出处:

Zhenhua Li, Shiqi Hu, Ke Huang, et.al. Targeted anti–IL-1β platelet microparticles for cardiac detoxing and repair. Science Advances  05 Feb 2020: Vol. 6, no. 6, eaay0589

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