State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China; School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan.
J Control Release. 2021 Jul 10;335:637-649. doi: 10.1016/j.jconrel.2021.05.044. Epub 2021 Jun 1.
Targeting a single molecule or a single pathway and poor drug delivery to the brain hamper the therapy of Alzheimer's disease (AD) based on abnormal metabolism of amyloid-β (Aβ). To solve these problems, we designed and synthesized a multi - strategy peptide (MOP), an ingenious apolipoprotein E mimetic peptide, which could reduce Aβ deposition via inhibiting Aβ aggregation and at the same time accelerate Aβ clearance. Meanwhile, MOP could be self-assembled into different nanostructure, thus we constructed a multifunctional delivery system (APND-3) based on MOP self-assembled nanorods (aspect ratios of 3) that was a favorable morphology to enhance the permeation across the blood brain barrier (BBB) to address the poor delivery to brain issues. Besides, the drug delivery system introduces polydopamine (PDA) and COG1410 ligand as a shell to keep the favorable morphology of core and enhance the BBB targeting efficiency. As a result, the delivery system significantly enhances the delivery of MOP to the brain, thus reducing Aβ deposition, mitigating the memory deficits, and ameliorating neurologic damage in AD model mice. Our findings suggest that our drug and carrier integrated multifunctional delivery system has the potential for AD treatment.
针对阿尔茨海默病（AD）基于淀粉样蛋白-β（Aβ）代谢异常的单一分子或单一途径靶向治疗以及脑内药物递送效率差的问题，我们设计并合成了一种多策略肽（MOP），一种巧妙的载脂蛋白 E 模拟肽，可通过抑制 Aβ聚集来减少 Aβ沉积，同时加速 Aβ清除。同时，MOP 可以自组装成不同的纳米结构，因此我们构建了一种基于 MOP 自组装纳米棒（纵横比为 3）的多功能递药系统（APND-3），这种纳米棒的形态有利于增强穿过血脑屏障（BBB）的通透性，从而解决脑内递送效率差的问题。此外，该递药系统引入了聚多巴胺（PDA）和 COG1410 配体作为外壳，以保持核心的有利形态并提高 BBB 靶向效率。结果，该递药系统显著增强了 MOP 向大脑的递送，从而减少 Aβ沉积，减轻 AD 模型小鼠的记忆缺陷和神经损伤。我们的研究结果表明，我们的药物和载体集成的多功能递药系统具有治疗 AD 的潜力。
