Guan Pengpeng, Yuan Caijie, Li Jiali, Yu Kun, Xie Ruiqi, Hu Enling, Ding Weiwei, Lan Guangqian, Lu Fei
State Key Laboratory of Laboratory of Resource Insects, College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing 400715, China; Chongqing Engineering Research Center of Biomaterial Fiber and Modern Textile, Chongqing 400715, China.
Division of Trauma and Surgical Intensive Care Unit, Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China.
Int J Biol Macromol. 2024 Dec;282(Pt 2):136866. doi: 10.1016/j.ijbiomac.2024.136866. Epub 2024 Oct 23.
In the treatment of thrombosis, conventional nanocarriers inevitably have problems, such as adverse reactions and difficulties in synthesis. Inspired by the concept of 'medicine food homology,' we extracted and purified natural exosomes from mulberry leaves as carriers for the delivery of urokinase-type plasminogen activator (uPA) for targeted therapy. The obtained mulberry leaf exosomes (MLE) possessed a desirable hydrodynamic particle size (119.4 nm), a uniform size distribution (polydispersity index = 0.174), and a negative surface charge (-23.3 mv). Before loading with uPA, MLE were grafted with cyclic RGD (cRGD) to selectively bind activated platelets for thrombus targeting. The cytometry studies revealed that MLE@cRGD has a high thrombus targeting ability about 74.3 %. Animal tests demonstrated that the delivered uPA could dissolve clots almost completely in femoral vein thrombosis models. In addition, MLE could remodel venous microenvironments by effectively eliminating reactive oxygen species (ROS) and promoting the phenotypic transformation of macrophages from M1 to M2 for venous tissue repair.
在血栓治疗中，传统纳米载体不可避免地存在不良反应和合成困难等问题。受“药食同源”概念启发，我们从桑叶中提取并纯化天然外泌体，作为尿激酶型纤溶酶原激活剂（uPA）靶向治疗的递送载体。所获得的桑叶外泌体（MLE）具有理想的流体动力学粒径（119.4 nm）、均匀的粒径分布（多分散指数 = 0.174）和负表面电荷（-23.3 mv）。在装载uPA之前，将MLE与环RGD（cRGD）接枝，以选择性结合活化血小板用于血栓靶向。细胞计数研究表明，MLE@cRGD具有约74.3%的高血栓靶向能力。动物试验表明，递送的uPA在股静脉血栓形成模型中几乎可以完全溶解血栓。此外，MLE可以通过有效消除活性氧（ROS）并促进巨噬细胞从M1型向M2型的表型转化来重塑静脉微环境，以修复静脉组织。
