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具有基因沉默和抗炎作用的双重功能杂化纳米粒子。

Dual-function hybrid nanoparticles with gene silencing and anti-inflammatory effects.

机构信息

Department of Neurology, University of South Florida, 13220 USF Laurel Drive, Room 4105, Tampa, FL 33612, USA.

出版信息

Nanomedicine (Lond). 2022 Apr;17(9):577-590. doi: 10.2217/nnm-2021-0458. Epub 2022 Apr 4.

Abstract

Nanocarriers loaded with siRNA can be administered intranasally to provide a noninvasive, safe alternative to direct intracerebral or intrathecal infusions. Dual-function nanocarriers can also be designed to deliver several payloads that address different components of the pathological process. To design and test a hybrid nanocarrier with the capacity to lower Huntington's Disease gene () expression and prevent or diminish inflammation. Novel hybrid nanoparticles were fabricated using a chitosan-based matrix core loaded with siRNA and an outer shell consisting of a lipid composition containing cannabidiol. Incubation of hybrid nanoparticles in mesenchymal stem cell cultures obtained from a YAC128 transgenic mouse modeling Huntington's disease resulted in effective lowering of mutant gene expression and reduced levels of expression of the proinflammatory cytokine IL-6. A novel hybrid nanocarrier system with dual actions is effective in lowering gene expression and attenuating inflammatory processes.

摘要

载有 siRNA 的纳米载体可经鼻腔给药,为非侵入性、安全的替代方案,避免直接向脑内或鞘内输注。双功能纳米载体还可设计用于递送几种有效载荷,以解决病理过程的不同成分。 设计并测试一种具有降低亨廷顿病基因 () 表达和预防或减轻炎症能力的混合纳米载体。 使用壳聚糖基质核心负载 siRNA 并在外层壳中包含含有大麻二酚的脂质组成的新型混合纳米颗粒。 将混合纳米颗粒孵育于源自 YAC128 转基因小鼠模型亨廷顿病的间充质干细胞培养物中,导致突变基因表达有效降低,促炎细胞因子 IL-6 的表达水平降低。 具有双重作用的新型混合纳米载体系统可有效降低基因表达并减轻炎症过程。

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