脑靶向熊果酸纳米粒子用于蛛网膜下腔出血的抗铁锈色素沉着治疗。

IF 10.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of Nanobiotechnology Pub Date : 2024-10-18 DOI:10.1186/s12951-024-02866-x
Yong Li, Xinyi Zhu, Wei Xiong, Qingyu Zhao, Youdong Zhou, Yujia Guo, Baohui Liu, Mingchang Li, Qianxue Chen, Xiaobing Jiang, Yangzhi Qi, Qingsong Ye, Gang Deng
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Hyaluronic acid-coated ursolic acid nanoparticles (HA-PEG-UA NPs) were prepared using the solvent evaporation method. We investigated the in vivo distribution of HA-PEG-UA NPs in SAH model through IVIS and fluorescence observation, and examined their impact on short-term neurological function and cortical neurological injury. Finally, we assessed the effect of UA on the Nrf-2/SLC7A11/GPX4 axis via Western Blot analysis.</p><p><strong>Results: </strong>We successfully developed self-assembled UA NPs with hyaluronic acid to target the increased CD44 expression in the SAH-afflicted brain. The resulting HA-PEG-UA NPs facilitated delivery and enrichment of UA within the SAH-affected region. The targeted delivery of UA to the SAH region can effectively inhibit neuronal ferroptosis, improve neurological deficits, and prognosis in mice. 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引用次数: 0

摘要

背景:蛛网膜下腔出血(SAH)是一种危及生命的脑血管疾病,早期脑损伤(EBI)是导致患者死亡和不良预后的主要因素。神经元铁变态反应是导致 SAH 早期脑损伤的关键病理机制。针对嗜铁细胞增多症干预SAH的治疗策略前景广阔:方法:通过血管内穿刺诱导 SAH 模型,并使用 FJC 染色、普鲁士蓝染色以及丙二醛(MDA)和谷胱甘肽(GSH)测定定量评估 SAH 早期神经元铁突变的存在。我们采用溶剂蒸发法制备了透明质酸包覆熊果酸的纳米颗粒(HA-PEG-UA NPs)。我们通过IVIS和荧光观察研究了HA-PEG-UA NPs在SAH模型中的体内分布,并考察了它们对短期神经功能和皮层神经损伤的影响。最后,我们通过 Western Blot 分析评估了 UA 对 Nrf-2/SLC7A11/GPX4 轴的影响:结果:我们成功开发出了与透明质酸自组装的 UA NPs,以针对 SAH 患者大脑中 CD44 表达的增加。由此产生的HA-PEG-UA NPs促进了UA在SAH影响区域内的递送和富集。向SAH区域靶向递送UA能有效抑制小鼠神经元铁凋亡,改善神经功能缺损和预后。其作用机制与激活Nrf-2/SLC7A11/GPX4信号通路有关:脑靶向HA-PEG-UA NPs研制成功,有望通过调节Nrf-2/SLC7A11/GPX4信号限制神经元铁凋亡,从而改善SAH预后。
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Brain-targeted ursolic acid nanoparticles for anti-ferroptosis therapy in subarachnoid hemorrhage.

Background: Subarachnoid hemorrhage (SAH) is a life -threatening cerebrovascular disease, where early brain injury (EBI) stands as a primary contributor to mortality and unfavorable patient outcomes. Neuronal ferroptosis emerges as a key pathological mechanism underlying EBI in SAH. Targeting ferroptosis for therapeutic intervention in SAH holds significant promise as a treatment strategy.

Methods: SAH model was induced via intravascular puncture and quantitatively assessed the presence of neuronal ferroptosis in the early phase of SAH using FJC staining, Prussian blue staining, as well as malondialdehyde (MDA) and glutathione (GSH) measurements. Hyaluronic acid-coated ursolic acid nanoparticles (HA-PEG-UA NPs) were prepared using the solvent evaporation method. We investigated the in vivo distribution of HA-PEG-UA NPs in SAH model through IVIS and fluorescence observation, and examined their impact on short-term neurological function and cortical neurological injury. Finally, we assessed the effect of UA on the Nrf-2/SLC7A11/GPX4 axis via Western Blot analysis.

Results: We successfully developed self-assembled UA NPs with hyaluronic acid to target the increased CD44 expression in the SAH-afflicted brain. The resulting HA-PEG-UA NPs facilitated delivery and enrichment of UA within the SAH-affected region. The targeted delivery of UA to the SAH region can effectively inhibit neuronal ferroptosis, improve neurological deficits, and prognosis in mice. Its mechanism of action is associated with the activation of the Nrf-2/SLC7A11/GPX4 signaling pathway.

Conclusions: Brain-targeted HA-PEG-UA NPs was successfully developed and hold the potential to enhance SAH prognosis by limiting neuronal ferroptosis via modulation of the Nrf-2/SLC7A11/GPX4 signal.

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来源期刊
Journal of Nanobiotechnology
Journal of Nanobiotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
13.90
自引率
4.90%
发文量
493
审稿时长
16 weeks
期刊介绍: Journal of Nanobiotechnology is an open access peer-reviewed journal communicating scientific and technological advances in the fields of medicine and biology, with an emphasis in their interface with nanoscale sciences. The journal provides biomedical scientists and the international biotechnology business community with the latest developments in the growing field of Nanobiotechnology.
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