Functionalized Nanozyme Microcapsules Targeting Deafness Prevention via Mitochondrial Homeostasis Remodeling

IF 27.4 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Shengjie Ge, Aidong Sun, Xinyu Zhou, Ping Niu, Yong Chen, Xiaotao Bao, Meng Yu, Zhenhua Zhong, Jingwu Sun, Guang Li
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Abstract

Mitochondrial dysfunction, which is the primary mechanism underlying cisplatin-induced hearing loss, can potentially be mitigated by modulating the redox balance and reprogramming the energy metabolism to remodel mitochondrial homeostasis. Herein, N-acetyl-l-cysteine–derived carbonized polymer dots (NAC CPDs) are embedded into manganese porphyrin–doped metal–organic frameworks and encapsulated using a polydopamine (PDA) coating and gelatin methacryloyl (GelMA) hydrogel to afford functionalized nanozyme microcapsules. Owing to their injectability and adhesion properties, these microcapsules exhibit the advantages of prolonged retention in the middle ear and sustained release in the inner ear. The synergy between the manganese porphyrin and polymer dots results in excellent antioxidant properties. The developed nanozymes activate the PI3K-AKT pathway, reprogramming the energy supply mechanism, and inhibiting the oligomerization of BAX in mitochondria to prevent the leakage of mitochondrial DNA and cytochrome c. Therapeutic efficacy and related mechanisms are validated in vivo. Thus, this study on mitochondrial homeostasis remodeling by nanozyme microcapsules opens a new chapter in the treatment of hearing loss.

Abstract Image

Abstract Image

功能化纳米酶微胶囊通过线粒体稳态重塑预防耳聋
线粒体功能障碍是顺铂引起的听力损失的主要机制,可以通过调节氧化还原平衡和重编程能量代谢来重塑线粒体稳态来减轻线粒体功能障碍。本研究将n -乙酰-l-半胱氨酸衍生的碳化聚合物点(NAC CPDs)嵌入到锰卟啉掺杂的金属有机框架中,并使用聚多巴胺(PDA)涂层和明胶甲基丙烯酰(GelMA)水凝胶进行封装,从而获得功能化的纳米酶微胶囊。由于它们的可注射性和粘附性,这些微胶囊具有在中耳中长时间滞留和在内耳中持续释放的优点。卟啉锰与聚合物点之间的协同作用产生了优异的抗氧化性能。所开发的纳米酶激活PI3K-AKT通路,重新编程能量供应机制,抑制线粒体中BAX的寡聚,以防止线粒体DNA和细胞色素c的泄漏。体内实验验证了治疗效果和相关机制。因此,纳米酶微胶囊对线粒体稳态重塑的研究为听力损失的治疗开辟了新的篇章。
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来源期刊
Advanced Materials
Advanced Materials 工程技术-材料科学:综合
CiteScore
43.00
自引率
4.10%
发文量
2182
审稿时长
2 months
期刊介绍: Advanced Materials, one of the world's most prestigious journals and the foundation of the Advanced portfolio, is the home of choice for best-in-class materials science for more than 30 years. Following this fast-growing and interdisciplinary field, we are considering and publishing the most important discoveries on any and all materials from materials scientists, chemists, physicists, engineers as well as health and life scientists and bringing you the latest results and trends in modern materials-related research every week.
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