BACKGROUND Although many therapeutic strategies for Alzheimer's disease (AD) have been explored, these strategies are seldom used in the clinic. Therefore, AD therapeutic research is still urgently needed. One major challenge in the field of nanotherapeutics is to increase the selective delivery of drugs to a targeted location. Herein, we devised and tested a strategy for delivery of nanoparticles to neurons to inhibit tau aggregation by directly targeting p-tau. RESULTS Curcumin (CUR) is loaded onto red blood cell (RBC) membrane-coated PLGA particles bearing T807 molecules attached to the RBC membrane surface (T807/RPCNP). With the advantage of the suitable physicochemical properties of the PLGA nanoparticles and the unique biological functions of the RBC membrane, the RPCNP are stabilized and promote sustained CUR release, which provided improved biocompatibility and resulted in long-term presence in the circulation. Under the synergistic effects of T807, T807/RPCNP can not only effectively penetrate the blood-brain barrier (BBB), but they also possess high binding affinity to hyperphosphorylated tau in nerve cells where they inhibit multiple key pathways in tau-associated AD pathogenesis. When CUR was encapsulated, our data also demonstrated that CUR-loaded T807/RPCNP NPs can relieve AD symptoms by reducing p-tau levels and suppressing neuronal-like cells death both in vitro and in vivo. The memory impairment observed in an AD mouse model is significantly improved following systemic administration of CUR-loaded T807/RPCNP NPs. CONCLUSION Intravenous neuronal tau-targeted T807-modified novel biomimetic nanosystems are a promising clinical candidate for the treatment of AD.

中文翻译：

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神经元 tau 蛋白靶向仿生纳米粒子用于递送姜黄素以延缓阿尔茨海默病的进展。

背景技术虽然已经探索了许多针对阿尔茨海默病(AD)的治疗策略，但这些策略很少在临床中使用。因此，AD治疗研究仍然迫切需要。纳米治疗领域的一项主要挑战是增加药物向目标位置的选择性递送。在此，我们设计并测试了一种将纳米颗粒递送至神经元的策略，通过直接靶向 p-tau 来抑制 tau 聚集。结果 姜黄素 (CUR) 被负载到红细胞 (RBC) 膜包被的 PLGA 颗粒上，该颗粒带有附着在 RBC 膜表面 (T807/RPCNP) 的 T807 分子。凭借PLGA纳米粒子合适的理化性质和红细胞膜独特的生物学功能，RPCNP得到稳定并促进CUR持续释放，从而改善了生物相容性并导致在循环中长期存在。在T807的协同作用下，T807/RPCNP不仅可以有效穿透血脑屏障（BBB），而且还与神经细胞中过度磷酸化的tau蛋白具有高结合亲和力，从而抑制tau蛋白相关AD发病机制中的多个关键通路。当 CUR 被封装时，我们的数据还表明，负载 CUR 的 T807/RPCNP NP 可以通过降低体内和体外 p-tau 水平并抑制神经元样细胞死亡来缓解 AD 症状。在 AD 小鼠模型中观察到的记忆障碍在全身施用 CUR 负载的 T807/RPCNP NP 后显着改善。结论 静脉注射神经元 tau 靶向 T807 修饰的新型仿生纳米系统是治疗 AD 的有前途的临床候选药物。