Neuron tau-targeting biomimetic nanoparticles for curcumin delivery to delay progression of Alzheimer's disease (Retracted Article)
Neuron tau-targeting biomimetic nanoparticles for curcumin delivery to delay progression of Alzheimer's disease (Retracted Article)
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DOI：
10.1186/s12951-020-00626-1
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发表时间：
2020-05-13
影响因子：
10.2
通讯作者：
Yang, Yang
中科院分区：
文献类型：
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作者：
Gao, Chunhong;Chu, Xiaoyang;Yang, Yang
背景：虽然已经探索了许多阿尔茨海默病（AD）的治疗策略，但这些策略很少用于临床。因此，阿尔茨海默病的治疗研究仍然迫切需要。纳米治疗领域的一个主要挑战是增加药物的选择性递送到目标位置。在此，我们设计并测试了一种将纳米颗粒递送到神经元的策略，通过直接靶向p-tau来抑制tau聚集。结果姜黄素（Curcumin， CUR）被负载在红细胞（RBC）膜包被的PLGA颗粒上，该颗粒携带T807分子，并附着在红细胞膜表面（T807/RPCNP）。利用PLGA纳米颗粒适宜的物理化学性质和红细胞膜独特的生物学功能，RPCNP稳定并促进CUR的持续释放，从而提供了更好的生物相容性，并导致长期存在于循环中。在T807的协同作用下，T807/RPCNP不仅能有效穿透血脑屏障（BBB），而且对神经细胞中过度磷酸化的tau具有高结合亲和力，抑制tau相关AD发病的多个关键通路。当包封CUR时，我们的数据还表明，在体外和体内，加载CUR的T807/RPCNP NPs可以通过降低p-tau水平和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损伤在系统给药cur负载的T807/RPCNP NPs后显着改善。结论静脉注射神经元靶向t807修饰的新型仿生纳米系统是治疗阿尔茨海默病的一种有前景的临床候选药物。
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.