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向的H2S输送系统通过重塑费里替诺法基路径,减轻脊髓损伤后血液脊髓屏障的破坏

Zhiheng Chen¹, Xinkai Pu¹, Ruiyang Li²

¹Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|March 10, 2026

概括

这项研究引入了一种新型纳米粒子,该纳米粒子提供硫化 (H2S),用于在脊髓损伤 (SCI) 后修复血脊髓屏障 (BSCB). 这种H2S释放疗法减少了氧化应激和铁,促进了BSCB完整性和潜在的SCI治疗.

科学领域:

神经科学是一个神经科学.
生物医学工程生物医学工程
纳米技术纳米技术

背景情况:

脊髓损伤 (SCI) 导致严重的神经缺陷,通常由血脊髓屏障 (BSCB) 的破坏加剧.
BSCB对于维持脊髓平衡至关重要,其受损的完整性有助于二次损伤的进展.
硫化 (H2S) 在各种血管疾病中表现出保护作用,表明其治疗潜力.

研究的目的:

开发和评估一种静脉注射纳米粒子,SPRC@MPDA-RGD,用于针对性地向SCI后被破坏的BSCB提供.
研究纳米粒子的治疗机制,重点关注H2S生产,反应性氧物种 (ROS) 清除和铁灭抑制.
评估这种纳米治疗策略在促进BSCB修复和治疗SCI方面的潜力.

主要方法:

工程SPRC@MPDA-RGD纳米粒子与c(RGDyK) 功能化,以准SCI内皮细胞上过度表达的αvβ3整体素.
纳米粒子提供S-propargyl-cysteine (SPRC) 来刺激内源H2S的产生和清理ROS.
研究PI3K/Akt/mTOR通路的激活,抑制ferritinophagy,并减少铁亡.

主要成果:

SPRC@MPDA-RGD纳米粒子成功地准了被破坏的BSCB.
释放的SPRC上调了cystathionine γ-lyase (CSE),导致内源H2S产量增加和ROS清理.
产生H2S激活PI3K/Akt/mTOR通路,抑制ferritinophagy和ferroptosis,最终保护BSCB.

结论:

开发的纳米治疗策略有效地协调H2S生产和ROS清理,以减轻SCI后的二次损伤.
纳米颗粒对铁代和铁代的抑制促进了BSCB的修复.
SPRC@MPDA-RGD显示出作为治疗脊髓损伤治疗的新型治疗方法的巨大潜力.

关键词:

在H2S中,它是H2S.血液脊髓障碍物血液脊髓障碍物脊髓障碍物费里丁食 (ferritinophagy) 是一种脊髓损伤导致的脊髓损伤有针对性的纳米粒子.

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