Acharya Basanta, McGlade Caylie A, Yin Haifeng, Kawano Tomohiro, Haar Lauren, Mackman Nigel, Sellers Rani S, Tan Xianming, Bhatt Aadra P, Lawrence David S, Vickerman Brianna M
Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
J Control Release. 2025 Feb 10;378:281-293. doi: 10.1016/j.jconrel.2024.11.059. Epub 2024 Dec 17.
Occlusive blood clots remain a significant global health challenge and result in emergencies that are main causes of death and disability worldwide. Thrombolytic agents (including tissue plasminogen activator, tPA) are the only pharmacological means to dissolve blood clots. However, these drugs have modest efficacy and severe safety concerns persist. We have developed light-responsive tPA-loaded red blood cells (tPA-RBCs) to target thrombolytic activity at the site of a blood clot. Herein, we describe the use of light to control the release of tPA from engineered RBCs and the subsequent degradation of a blood clot ex vivo. Furthermore, we have employed this technology to restore blood flow to an occluded mouse artery in vivo using a targeted dose that is 25 times lower than conventional systemic tPA treatment.
闭塞性血凝块仍然是一项重大的全球健康挑战,会引发紧急情况,而这些紧急情况是全球范围内死亡和残疾的主要原因。溶栓剂(包括组织纤溶酶原激活剂,tPA)是溶解血凝块的唯一药物手段。然而,这些药物疗效一般,且严重的安全性问题依然存在。我们已经研发出负载有光响应性tPA的红细胞(tPA-RBCs),以将溶栓活性靶向血凝块部位。在此,我们描述了利用光来控制工程化红细胞中tPA的释放以及随后体外血凝块的降解。此外,我们已运用这项技术,通过使用比传统全身tPA治疗低25倍的靶向剂量,在体内恢复闭塞小鼠动脉的血流。