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Nanoarmour-shielded single-cell factory for bacteriotherapy of Parkinson's disease
Journal of Controlled Release ( IF 10.8 ) Pub Date : 2021-09-10 , DOI: 10.1016/j.jconrel.2021.09.009
Xin Zhou 1 , Qinglu Guo 2 , Mingming Guo 2 , Bowen Li 2 , Wenchang Peng 2 , Deping Wang 1 , Dong Ming 2 , Bin Zheng 3
Affiliation  

Cell-based therapy for Parkinson's disease (PD) is a novel and promising approach in recent years. However, exogenous cells are easy to be captured and destroyed by the harsh environment in vivo, so their application prospects have been severely limited. Here, a facile yet versatile approach for decorating individual living cells with nano-armor coatings is reported. By simply self-assembly with liposome under a cyto-compatible condition, the lipid bimolecular coating on the surface of each cell acts as armor to effectively protect it from the attack and destruction of strong acids and digestive enzymes during the oral treatment of PD. Our results demonstrated that the liposome coated B. adolescentis (LCB) could significantly improve the colonization rate in the intestinal tract. LCB, as a living cell factory, can self-regulate to produce a constant concentration of γ-aminobutyric acid and maintain a longer half-life for the treatment of PD. Then, we also explored the specific mechanism of LCB to improve the behavior of murine models of PD, including abating inflammatory effects, reducing neuronal apoptosis, regulating the activity of dopaminergic neurons and microglia. The simple nano-armor shielded single-cell factory can produce neurotransmitters-like drugs on demand in vivo, introducing novel strategies of integration of producing and using to the research of drug delivery field.



中文翻译:

用于帕金森病细菌治疗的纳米装甲单细胞工厂

近年来,帕金森病 (PD) 的细胞疗法是一种新颖且有前景的方法。然而,外源细胞在体内恶劣的环境容易被捕获和破坏,因此其应用前景受到严重限制。在这里,报道了一种用纳米装甲涂层装饰单个活细胞的简便而通用的方法。通过在细胞相容条件下与脂质体简单自组装,每个细胞表面的脂质双分子涂层充当盔甲,有效保护其在口服治疗PD期间免受强酸和消化酶的攻击和破坏。我们的结果表明脂质体包被B.teenis(LCB) 可显着提高肠道定植率。LCB作为活细胞工厂,可以自我调节产生恒定浓度的γ-氨基丁酸,维持较长的半衰期,用于治疗PD。然后,我们还探讨了 LCB 改善 PD 小鼠模型行为的具体机制,包括减轻炎症作用、减少神经元凋亡、调节多巴胺能神经元和小胶质细胞的活性。简单的纳米装甲屏蔽单细胞工厂可以在体内按需生产类神经递质药物,为药物递送领域的研究引入了产用一体化的新策略。

更新日期:2021-09-15
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