The precise and targeted delivery of therapeutic agents to the lesion sites remains a major challenge in treating brain diseases represented by ischemic stroke. Herein, we modified liposomes with mesenchymal stem cells (MSC) membrane to construct biomimetic liposomes, termed MSCsome. MSCsome (115.99 ± 4.03 nm) exhibited concentrated accumulation in the cerebral infarcted hemisphere of mice with cerebral ischemia-reperfusion injury, while showing uniform distribution in the two cerebral hemispheres of normal mice. Moreover, MSCsome exhibited high colocalization with damaged nerve cells in the infarcted hemisphere, highlighting its advantageous precise targeting capabilities over liposomes at both the tissue and cellular levels. Leveraging its superior targeting properties, MSCsome effectively delivered Dl-3-n-butylphthalide (NBP) to the injured hemisphere, making a single-dose (15 mg/kg) intravenous injection of NBP-encapsulated MSCsome facilitate the recovery of motor functions in model mice by improving the damaged microenvironment and suppressing neuroinflammation. This study underscores that the modification of the MSC membrane notably enhances the capacity of liposomes for precisely targeting the injured hemisphere, which is particularly crucial in treating cerebral ischemia-reperfusion injury.

中文翻译：

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基于间充质干细胞的仿生脂质体精确靶向药物递送至脑缺血再灌注损伤的半球


将治疗剂精确且有针对性地递送至病变部位仍然是治疗以缺血性中风为代表的脑部疾病的主要挑战。在此，我们用间充质干细胞（MSC）膜修饰脂质体，构建仿生脂质体，称为MSCsome。 MSCsome（115.99±4.03nm）在脑缺血再灌注损伤小鼠的脑梗塞半球集中聚集，而在正常小鼠的两个大脑半球中呈现均匀分布。此外，MSCsome 与梗塞半球受损神经细胞表现出高度共定位，凸显了其在组织和细胞水平上优于脂质体的精确靶向能力。利用其卓越的靶向特性，MSCsome 有效地将 Dl-3-n-丁基苯酞 (NBP) 递送至受伤的半球，使得单剂量（15 mg/kg）静脉注射 NBP 封装的 MSCsome 有助于模型中运动功能的恢复通过改善小鼠受损的微环境和抑制神经炎症。这项研究强调，间充质干细胞膜的修饰显着增强了脂质体精确靶向受损半球的能力，这对于治疗脑缺血再灌注损伤尤为重要。