Department of Pharmacy, Xijing Hospital, Air Force Medical University, Changle West Road 127, Xi'an, Shaanxi, China.
Department of Geriatrics, Xijing Hospital, Air Force Medical University, Changle West Road 127, Xi'an, Shaanxi, China.
J Nanobiotechnology. 2024 Jul 4;22(1):393. doi: 10.1186/s12951-024-02641-y.
The therapeutic strategies for acute ischemic stroke were faced with substantial constraints, emphasizing the necessity to safeguard neuronal cells during cerebral ischemia to reduce neurological impairments and enhance recovery outcomes. Despite its potential as a neuroprotective agent in stroke treatment, Chikusetsu saponin IVa encounters numerous challenges in clinical application.
Brain-targeted liposomes modified with THRre peptides showed substantial uptake by bEnd. 3 and PC-12 cells and demonstrated the ability to cross an in vitro blood-brain barrier model, subsequently accumulating in PC-12 cells. In vivo, they could significantly accumulate in rat brain. Treatment with C-IVa-LPs-THRre notably reduced the expression of proteins in the P2RX7/NLRP3/Caspase-1 pathway and inflammatory factors. This was evidenced by decreased cerebral infarct size and improved neurological function in MCAO rats.
The findings indicate that C-IVa-LPs-THRre could serve as a promising strategy for targeting cerebral ischemia. This approach enhances drug concentration in the brain, mitigates pyroptosis, and improves the neuroinflammatory response associated with stroke.
急性缺血性脑卒中的治疗策略受到了很大的限制，强调有必要在脑缺血期间保护神经元细胞，以减少神经损伤并提高恢复效果。尽管柴胡皂甙 IVa 作为脑卒中治疗中的一种神经保护剂具有潜力，但在临床应用中却面临着诸多挑战。
THRre 肽修饰的脑靶向脂质体被 bEnd.3 和 PC-12 细胞大量摄取，并表现出穿过体外血脑屏障模型的能力，随后在 PC-12 细胞中积累。在体内，它们可以显著积聚在大鼠的大脑中。用 C-IVa-LPs-THRre 治疗明显降低了 P2RX7/NLRP3/Caspase-1 通路和炎症因子中蛋白的表达。这在 MCAO 大鼠的脑梗死面积减小和神经功能改善方面得到了证实。
研究结果表明，C-IVa-LPs-THRre 可能是一种有前途的靶向脑缺血的策略。这种方法增加了脑内的药物浓度，减轻了细胞焦亡，并改善了与脑卒中相关的神经炎症反应。
