Ph.D. Program in Translational Medicine, National Taiwan University and Academia Sinica, Taipei, Taiwan.
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
Sci Adv. 2021 Apr 23;7(17). doi: 10.1126/sciadv.abf2400. Print 2021 Apr.
The delivery of therapeutics through the circulatory system is one of the least arduous and less invasive interventions; however, this approach is hampered by low vascular density or permeability. In this study, by exploiting the ability of monocytes to actively penetrate into diseased sites, we designed aptamer-based lipid nanovectors that actively bind onto the surface of monocytes and are released upon reaching the diseased sites. Our method was thoroughly assessed through treating two of the top causes of death in the world, cardiac ischemia-reperfusion injury and pancreatic ductal adenocarcinoma with or without liver metastasis, and showed a significant increase in survival and healing with no toxicity to the liver and kidneys in either case, indicating the success and ubiquity of our platform. We believe that this system provides a new therapeutic method, which can potentially be adapted to treat a myriad of diseases that involve monocyte recruitment in their pathophysiology.
通过循环系统输送治疗剂是最不费力和侵入性最小的干预方法之一;然而,这种方法受到血管密度或通透性低的限制。在这项研究中,我们利用单核细胞主动渗透到病变部位的能力,设计了基于适配体的脂质纳米载体,这些载体能够主动结合到单核细胞的表面,并在到达病变部位时释放出来。我们的方法通过治疗世界上两种主要的死亡原因——心肌缺血再灌注损伤和胰腺导管腺癌(伴或不伴肝转移)进行了全面评估,结果显示,无论是在肝还是肾,这种方法都显著提高了存活率和治愈率,且没有毒性,这表明我们的平台是成功且普遍适用的。我们相信,这种系统提供了一种新的治疗方法,可能适用于治疗涉及单核细胞在其病理生理学中募集的多种疾病。