School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing 211166, P. R. China.
State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, P. R. China.
ACS Appl Mater Interfaces. 2021 Sep 22;13(37):43880-43891. doi: 10.1021/acsami.1c06014. Epub 2021 Sep 8.
Early lesion site diagnosis and neuroprotection are crucial to the theranostics of acute ischemic stroke. Xenon (Xe), as a nontoxic gaseous neuroprotectant, holds great promise for ischemic stroke therapy. In this study, Xe-encapsulated lipid nanobubbles (Xe-NBs) have been prepared for the real-time ultrasound image-guided preemptive treatment of the early stroke. The lipids are self-assembled at the interface of free Xe bubbles, and the mean diameter of Xe-NBs is 225 ± 11 nm with a Xe content of 73 ± 2 μL/mL. The results show that Xe-NBs can protect oxygen/glucose-deprived PC12 cells against apoptosis and oxidative stress. Based on the ischemic stroke mice model, the biodistribution, timely ultrasound imaging, and the therapeutic effects of Xe-NBs for stroke lesions were investigated . The accumulation of Xe-NBs to the ischemic lesion endows ultrasound contrast imaging with the lesion area. The cerebral blood flow measurement indicates that the administration of Xe-NBs can improve microcirculatory restoration, resulting in reduced acute microvascular injury in the lesion area. Furthermore, local delivery of therapeutic Xe can significantly reduce the volume of cerebral infarction and restore the neurological function with reduced neuron injury against apoptosis. Therefore, Xe-NBs provide a novel nanosystem for the safe and rapid theranostics of acute ischemic stroke, which is promising to translate into the clinical management of stroke.
早期病变部位的诊断和神经保护对于急性缺血性脑卒中的治疗至关重要。氙气（Xe）作为一种无毒的气体神经保护剂，为缺血性脑卒中的治疗带来了很大的希望。在这项研究中，制备了氙气包封脂质纳米气泡（Xe-NBs），用于实时超声图像引导的早期脑卒中的预防性治疗。脂质在自由 Xe 气泡的界面处自组装，Xe-NBs 的平均直径为 225±11nm，Xe 含量为 73±2μL/mL。结果表明，Xe-NBs 可以保护氧/葡萄糖剥夺的 PC12 细胞免受细胞凋亡和氧化应激的影响。基于缺血性脑卒中小鼠模型，研究了 Xe-NBs 的体内分布、实时超声成像以及对脑卒中病变的治疗效果。Xe-NBs 对缺血性病变的积累使超声对比成像具有病变区域的特点。脑血流测量表明，Xe-NBs 的给药可以改善微循环的恢复，从而减少病变区域的急性微血管损伤。此外，局部给予治疗性 Xe 可以显著减少脑梗死的体积，并恢复神经功能，减少神经元凋亡引起的损伤。因此，Xe-NBs 为急性缺血性脑卒中的安全快速治疗提供了一种新的纳米系统，有望转化为脑卒中的临床治疗管理。
