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工程化纳米酶中的双活性位点和缺陷结构以重编程颌骨微环境用于放射性骨坏死治疗

Engineering Dual Active Sites and Defect Structure in Nanozymes to Reprogram Jawbone Microenvironment for Osteoradionecrosis Therapy.

作者信息

Cheng Zheng, Wang Yuchen, Lin Haobo, Chen Ziyu, Qin Ran, Wang Tianxiao, Xu Hang, Du Yifei, Yuan Hua, Pan Yongchu, Jiang Huijun, Jiang Xinquan, Jiang Jiandong, Wu Fan, Wang Yuli

机构信息

Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Nanjing Medical University, State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.

Medical Basic Research Innovation Centre for Cardiovascular and Cerebrovascular Diseases, Ministry of Education, International Joint Laboratory for Drug Target of Critical Illnesses, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.

出版信息

Adv Sci (Weinh). 2025 Feb;12(6):e2413215. doi: 10.1002/advs.202413215. Epub 2024 Dec 17.

DOI:10.1002/advs.202413215
PMID:39686746
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11809426/
Abstract

Four to eight percent of patients with head and neck cancer will develop osteoradionecrosis of the jaw (ORNJ) after radiotherapy. Various radiation-induced tissue injuries are associated with reactive oxygen and nitrogen species (RONS) overproduction. Herein, Fe doping is used in VO (Fe-VO) nanozymes with multienzyme activities for ORNJ treatment via RONS scavenging. Fe doping can induce structure reconstruction of nanozymes with abundant defect production, including Fe substitution and oxygen vacancies (OVs), which markedly increased multiple enzyme-mimicking activity. Catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) enzyme-like performance of Fe-VO can effectively reprogram jawbone microenvironment to restore mitochondrial dysfunction and enhance mitophagy. Moreover, the surface plasmon resonance (SPR) effect of Fe-VO made it a good photothermal nanoagents for inhibiting jaw infection. Thus, this work demonstrated that Fe-VO nanozymes can efficiently scavenge RONS, activate mitophagy, and inhibit bacteria, which is potential for ORNJ treatment.

摘要

4%至8%的头颈癌患者在放疗后会发生颌骨放射性骨坏死（ORNJ）。各种辐射诱导的组织损伤都与活性氧和氮物种（RONS）的过量产生有关。在此，铁掺杂被用于具有多酶活性的VO（Fe-VO）纳米酶，通过清除RONS来治疗ORNJ。铁掺杂可以诱导纳米酶的结构重构，产生大量缺陷，包括铁取代和氧空位（OVs），这显著提高了多种酶模拟活性。Fe-VO的过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）样性能可以有效地重新编程颌骨微环境，以恢复线粒体功能障碍并增强线粒体自噬。此外，Fe-VO的表面等离子体共振（SPR）效应使其成为抑制颌部感染的良好光热纳米剂。因此，这项工作表明Fe-VO纳米酶可以有效地清除RONS、激活线粒体自噬并抑制细菌，在ORNJ治疗方面具有潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6585/11809426/d1dc70ae4ce6/ADVS-12-2413215-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6585/11809426/e27a8608b533/ADVS-12-2413215-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6585/11809426/45329f922f92/ADVS-12-2413215-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6585/11809426/e58a9e2f8582/ADVS-12-2413215-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6585/11809426/9d26c86e4efa/ADVS-12-2413215-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6585/11809426/b1fb190343b4/ADVS-12-2413215-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6585/11809426/17727b79e8da/ADVS-12-2413215-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6585/11809426/36f985e962d7/ADVS-12-2413215-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6585/11809426/29cfeb8f3bd8/ADVS-12-2413215-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6585/11809426/57fe8e3b9f3d/ADVS-12-2413215-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6585/11809426/d1dc70ae4ce6/ADVS-12-2413215-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6585/11809426/e27a8608b533/ADVS-12-2413215-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6585/11809426/45329f922f92/ADVS-12-2413215-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6585/11809426/e58a9e2f8582/ADVS-12-2413215-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6585/11809426/9d26c86e4efa/ADVS-12-2413215-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6585/11809426/b1fb190343b4/ADVS-12-2413215-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6585/11809426/17727b79e8da/ADVS-12-2413215-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6585/11809426/36f985e962d7/ADVS-12-2413215-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6585/11809426/29cfeb8f3bd8/ADVS-12-2413215-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6585/11809426/57fe8e3b9f3d/ADVS-12-2413215-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6585/11809426/d1dc70ae4ce6/ADVS-12-2413215-g004.jpg

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