Khang Min Kyung, Kuriakose Aneetta Elizabeth, Nguyen Tam, Co Cynthia My-Dung, Zhou Jun, Truong Thuy Thi Dang, Nguyen Kytai Truong, Tang Liping
Department of Bioengineering, University of Texas at Arlington, P.O. Box 19138, Arlington, Texas 76010, United States.
Department of Chemistry and Biochemistry, University of Texas at Arlington, Arlington, Texas 76010, United States.
ACS Biomater Sci Eng. 2020 Dec 14;6(12):6831-6841. doi: 10.1021/acsbiomaterials.0c00957. Epub 2020 Nov 10.
Arterial wall injury often leads to endothelium cell activation, endothelial detachment, and atherosclerosis plaque formation. While abundant research efforts have been placed on treating the end stages of the disease, no cure has been developed to repair injured and denude endothelium often occurred at an early stage of atherosclerosis. Here, a pretargeting cell delivery strategy using combined injured endothelial targeting nanoparticles and bioorthogonal click chemistry approach was developed to deliver endothelial cells to replenish the injured endothelium via a two-step process. First, nanoparticles bearing glycoprotein 1b α (Gp1bα) proteins and tetrazine (Tz) were fabricated to provide a homogeneous nanoparticle coating on an injured arterial wall via the interactions between Gp1bα and von Willebrand factor (vWF), a ligand that is present on denuded endothelium. Second, transplanted endothelium cells bearing transcyclooctene (TCO) would be quickly immobilized on the surfaces of nanoparticles via TCO:Tz reactions. binding studies under both static and flow conditions confirmed that our novel Tz-labeled Gp1bα-conjugated poly(lactic--glycolic acid) (PLGA) nanoparticles can successfully pretargeted toward the injured site and support rapid adhesion of endothelial cells from the circulation. results also confirm that such an approach is highly efficient in mediating the local delivery of endothelial cells at the sites of arterial injury. The results support that this pretargeting cell delivery approach may be used for repairing injured endothelium at its early stage.
动脉壁损伤常导致内皮细胞活化、内皮脱落和动脉粥样硬化斑块形成。尽管已经投入大量研究致力于治疗该疾病的终末期，但尚未开发出治愈方法来修复动脉粥样硬化早期经常出现的受损和剥脱的内皮。在此，开发了一种预靶向细胞递送策略，该策略使用联合的损伤内皮靶向纳米颗粒和生物正交点击化学方法，通过两步过程将内皮细胞递送至损伤部位以补充受损的内皮。首先，制备携带糖蛋白1bα（Gp1bα）蛋白和四嗪（Tz）的纳米颗粒，通过Gp1bα与血管性血友病因子（vWF）之间的相互作用，在受损动脉壁上提供均匀的纳米颗粒涂层，vWF是一种存在于剥脱内皮上的配体。其次，携带反式环辛烯（TCO）的移植内皮细胞将通过TCO:Tz反应快速固定在纳米颗粒表面。静态和流动条件下的结合研究证实，我们新型的Tz标记的Gp1bα共轭聚乳酸-乙醇酸共聚物（PLGA）纳米颗粒能够成功预靶向损伤部位，并支持循环中的内皮细胞快速黏附。结果还证实，这种方法在介导内皮细胞在动脉损伤部位的局部递送方面非常有效。这些结果支持这种预靶向细胞递送方法可用于在早期修复受损内皮。
