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有针对性的聚合体使得外周神经在受伤后能够得到更好的传递

Kayleigh Trumbull¹, Sophia Fetten², Noah Arnold¹

¹Department of Chemical and Biomolecular Engineering, Clemson University, Clemson, South Carolina 29634, United States.

Bioconjugate chemistry

|March 11, 2025

概括

向的聚合体提供了一种新的非侵入性方法,通过克服血神经屏障来治疗外周神经损伤. 像ApoE和RVG这样的体增强纳米粒子的传递和保留,以改善治疗结果.

科学领域:

生物医学工程生物医学工程
纳米技术纳米技术
再生医学是一种再生医学.

背景情况:

外周神经受伤往往需要侵入性手术修复,结果各不相同,较小的伤害没有得到治疗.
血神经屏障 (BNB) 阻碍了对神经的非侵入性药物输送,限制了治疗选择.
开发非侵入性策略,在全国范围内提供治疗方法,对于推进外围神经损伤治疗至关重要.

研究的目的:

为了研究结合体向聚合体在外围神经损伤后通过血神经屏障 (BNB) 进行非侵入性输送的疗效.
为了比较功能化聚合体与阿波利波蛋白E (ApoE) 和基于狂犬病病毒糖蛋白RVG29 (RVG) 的神经向和保留能力.
评估这些向纳米颗粒在增强治疗有效载荷向受伤的外围神经传递方面的潜力.

主要方法:

合成的聚乙烯甘醇 (PEG) - - 聚乳酸 (PLA) 聚合体载有AlexaFluor647染料.
与阿波利波蛋白E (ApoE) 或RVG29 (RVG) 结合的聚合体用于有针对性的输送.
在大鼠坐骨神经损伤模型中,通过神经内 (IN) 和肌内 (IM) 注射给药未标记,ApoE标记和RVG标记的聚合体.
量化光强度和分析的药物动力学参数,以评估输送,透和保留.

主要成果:

在IN注射后,ApoE和RVG标签都增强了IN注射后神经损伤部位的AlexaFluor647光,与未标记的对照组相比.
只有RVG标记的聚合体在IM注射后显著增加光,表明神经成功透.
活体分析显示,无论注射途径如何,ApoE标记的聚合体体实现了最高的有效载荷保留率.

结论:

用 ApoE 配体向炎症最大限度地提高了聚合体有效载荷的保留率,而用 RVG 配体向神经细胞则促进了整个 BNB 的更大透.
带功能化聚合体是对外围神经进行非侵入性治疗的有希望的策略.
这种方法有可能提高对外围神经损伤的治疗效率和可访问性.

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