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

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

doi:10.1002/advs.202413215

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

Adv Sci (Weinh). 2024 Dec 17:e2413215. doi: 10.1002/advs.202413215. Online ahead of print.

Authors

Zheng Cheng¹, Yuchen Wang¹, Haobo Lin¹, Ziyu Chen², Ran Qin¹, Tianxiao Wang², Hang Xu³, Yifei Du¹, Hua Yuan¹, Yongchu Pan⁴, Huijun Jiang², Xinquan Jiang⁵, Jiandong Jiang^{2

6}, Fan Wu², Yuli Wang^{1

2}

Affiliations

¹ 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.
² 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.
³ State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200120, China.
⁴ Department of Orthodontic, 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.
⁵ Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, China.
⁶ Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.

PMID: 39686746
DOI: 10.1002/advs.202413215

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_x (Fe-VO_x) 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_x can effectively reprogram jawbone microenvironment to restore mitochondrial dysfunction and enhance mitophagy. Moreover, the surface plasmon resonance (SPR) effect of Fe-VO_x made it a good photothermal nanoagents for inhibiting jaw infection. Thus, this work demonstrated that Fe-VO_x nanozymes can efficiently scavenge RONS, activate mitophagy, and inhibit bacteria, which is potential for ORNJ treatment.

Keywords: enzyme‐like performance; mitophagy; nanozymes; osteoradionecrosis of the jaw; reactive oxygen and nitrogen species.

Abstract

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