Department of Radiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People's Republic of China.
Chongqing Key Laboratory of Ultrasound Molecular Imaging & Department of Ultrasound, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People's Republic of China.
Int J Nanomedicine. 2022 May 4;17:2019-2039. doi: 10.2147/IJN.S357050. eCollection 2022.
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 FeO 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/cm 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.
动脉血栓形成是对人类健康的严重威胁。最近，许多血栓靶向纳米颗粒（NPs）被构建用于检测血栓或监测溶栓，但它们的血栓靶向性能有限。考虑到这一缺点，我们设计了一种具有增强血栓靶向能力的特定仿生系统。
在仿生系统中，明胶被选为载体，FeO 作为磁导航介质和磁共振（MR）成像剂。靶向纤维蛋白的 CREKA 肽被连接到明胶表面以制备靶向 NPs（TNPs），然后被巨噬细胞吞噬以构建仿生系统。在靶向部位，仿生系统在低强度聚焦超声（LIFU）照射下释放其内部的 TNPs。此外，通过共轭的 CREKA 肽进一步提高了靶向性能。
在这项研究中，我们成功构建了仿生系统，并在体外和体内证明了其靶向能力。结果表明，大多数 TNPs 在体外 2 W/cm 下 10 分钟的 LIFU 照射下从巨噬细胞中释放出来。此外，基于巨噬细胞对炎症性血栓的天然趋向性、磁导航和 CREKA 肽，验证了体外和体内的增强血栓靶向能力。此外，与仿生系统组相比，TNPs 处理组在 MR 图像中肝脾信号明显降低，荧光图像中肝脾信号明显增强，表明仿生系统比 TNPs 更不容易被网状内皮系统（RES）清除，这可能促进仿生系统在血栓部位的积累。
这些结果表明，具有 LIFU 响应性的磁引导仿生系统是一种靶向血栓的优秀候选物，有望成为溶栓治疗的创新药物递送系统。
