Magnet-Guided Bionic System with LIFU Responsiveness and Natural Thrombus Tropism for Enhanced Thrombus-Targeting Ability.
Magnet-Guided Bionic System with LIFU Responsiveness and Natural Thrombus Tropism for Enhanced Thrombus-Targeting Ability.
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具有 LIFU 响应性和自然血栓趋向性的磁引导仿生系统，可增强血栓靶向能力
DOI：
10.2147/ijn.s357050
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发表时间：
2022
影响因子：
8
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中科院分区：
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动脉血栓形成是严重威胁人类健康的疾病。近年来，许多血栓靶向纳米颗粒（NPs）被构建用于检测血栓或监测血栓溶解，但它们的血栓靶向性能有限。考虑到这一缺陷，我们设计了一种具有增强血栓靶向能力的仿生系统。在仿生系统中，选择明胶作为载体，Fe3O4作为磁导航介质和磁共振成像剂。将靶向纤维蛋白的CREKA肽偶联到明胶表面制备靶向NPs (TNPs)，然后被巨噬细胞吞噬以构建仿生系统。在目标部位，仿生系统在低强度聚焦超声（LIFU）照射下释放其内部TNPs。此外，结合的CREKA肽进一步提高了靶向性能。在这项研究中，我们成功构建了一个仿生系统，并在体外和体内证明了它的靶向能力。结果表明，体外2 W/cm2的LIFU照射10 min后，巨噬细胞释放出大部分TNPs。此外，基于巨噬细胞对炎性血栓的天然趋向性、磁导航和CREKA肽，增强的血栓靶向能力在体内和体外得到了验证。此外，与仿生系统组相比，TNPs组MR图像中肝脏和脾脏信号明显降低，荧光图像中肝脏和脾脏信号明显增强，表明仿生系统比TNPs更不容易被网状内皮系统（RES）清除，这可能促进了仿生系统在血栓部位的积累。这些结果表明，具有LIFU反应性的磁引导仿生系统是靶向血栓的优秀候选系统，有望成为溶栓治疗的创新药物输送系统。
Arterial thrombosis is a serious threat to human health. Recently, many thrombus-targeted nanoparticles (NPs) have been constructed for detecting thrombi or monitoring thrombolysis, but their thrombus-targeting performance is limited. Considering this drawback, we designed a specific bionic system with enhanced thrombus-targeting ability. In the bionic system, gelatin was chosen as a carrier, and Fe3O4 served as a magnetic navigation medium and a magnetic resonance (MR) imaging agent. The CREKA peptide, which targets fibrin, was conjugated to the surface of gelatin to prepare targeted NPs (TNPs), which were then engulfed by macrophages to construct the bionic system. At the targeted site, the bionic system released its interior TNPs under low-intensity focused ultrasound (LIFU) irradiation. Moreover, the targeting performance was further improved by the conjugated CREKA peptide. In this study, we successfully constructed a bionic system and demonstrated its targeting ability in vitro and in vivo. The results indicated that most TNPs were released from macrophages under LIFU irradiation at 2 W/cm2 for 10 min in vitro. Additionally, the enhanced thrombus-targeting ability, based on the natural tropism of macrophages toward inflammatory thrombi, magnetic navigation and the CREKA peptide, was verified ex vivo and in vivo. Moreover, compared with the bionic system group, the group treated with TNPs had significantly decreased liver and spleen signals in MR images and significantly enhanced liver and spleen signals in fluorescence images, indicating that the bionic system is less likely to be cleared by the reticuloendothelial system (RES) than TNPs, which may promote the accumulation of the bionic system at the site of the thrombus. These results suggest that the magnet-guided bionic system with LIFU responsiveness is an excellent candidate for targeting thrombi and holds promise as an innovative drug delivery system for thrombolytic therapy.