Metal-organic framework-edaravone nanoparticles for radiotherapy-induced brain injury treatment

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials Pub Date : 2024-09-30 DOI:10.1016/j.biomaterials.2024.122868

Xuejiao Li , Shiyuan Hua , Danni Zhong , Min Zhou , Zhongxiang Ding

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引用次数: 0

Abstract

Cranial radiotherapy may cause damage to normal brain tissues and induce cognitive dysfunction, so developing an effective strategy to prevent radiotherapy-induced brain injury is essential. Metal-organic frameworks (MOFs) can be used as vectors for the delivery of neuroprotective drugs due to their high drug loading capacity and low toxicity. In this study, we synthesized MIL-53(Cr) nanoparticles, which were used to deliver edaravone, and modified the surface of the nanoparticles with polyethylene glycol and Angiopep-2 (EDA@MIL-53(Cr)–P/A) to improve their oral bioavailability and ability to cross the blood–brain barrier (BBB). We confirmed that MIL-53(Cr)–P/A nanoparticles could achieve the sustained release of edaravone and enhance its ability to cross the BBB. The results of in vitro experiments showed that EDA@MIL-53(Cr)–P/A could exert radioprotective effects on HT22 and BV2 cells. We also demonstrated that EDA@MIL-53(Cr)–P/A could alleviate brain injury and cognitive dysfunction in mice receiving whole-brain irradiation. Mechanistically, EDA@MIL-53(Cr)–P/A alleviated irradiation-induced brain damage by inhibiting oxidative stress, DNA damage, apoptosis and inflammatory reactions. This study provides a new strategy for the protection against radiotherapy-induced brain injury.

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用于治疗放疗引起的脑损伤的金属有机框架-卡拉酮纳米粒子

颅脑放疗可能会对正常脑组织造成损伤并诱发认知功能障碍，因此开发一种有效的策略来预防放疗引起的脑损伤至关重要。金属有机框架（MOFs）具有高载药量和低毒性的特点，可用作神经保护药物的载体。在这项研究中，我们合成了用于递送依达拉奉的 MIL-53(Cr)纳米颗粒，并用聚乙二醇和 Angiopep-2 对纳米颗粒表面进行了修饰（EDA@MIL-53(Cr)-P/A），以提高其口服生物利用度和穿越血脑屏障（BBB）的能力。我们证实，MIL-53(Cr)-P/A 纳米颗粒可以实现依达拉奉的持续释放，并增强其穿越 BBB 的能力。体外实验结果表明，EDA@MIL-53(Cr)-P/A 对 HT22 和 BV2 细胞具有放射保护作用。我们还证实，EDA@MIL-53(Cr)-P/A 可减轻全脑辐照小鼠的脑损伤和认知功能障碍。从机理上讲，EDA@MIL-53(Cr)-P/A 通过抑制氧化应激、DNA 损伤、细胞凋亡和炎症反应，减轻了辐照诱导的脑损伤。这项研究为防止放疗引起的脑损伤提供了一种新策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomaterials 工程技术-材料科学：生物材料

CiteScore

26.00

自引率

2.90%

发文量

565

审稿时长

46 days

期刊介绍： Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.