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Theranostics 2022; 12(6):2658-2673. doi:10.7150/thno.64244 This issue Cite

Research Paper

Wound microenvironment-responsive glucose consumption and hydrogen peroxide generation synergistic with azithromycin for diabetic wounds healing

Minqi Shi^1,2, Zhen Du^1,3✉, Yuchen Qi², Wanlin Li², Huiqun Hu⁵, Xiuhui Lin⁵, Shoujie Wang^1,✉, Zhe Tang^1,✉, Min Zhou^1,2,4,✉

1. Department of Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 322000, China.
2. Institute of Translational Medicine, Zhejiang University, Hangzhou 310009, China.
3. The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.
4. State Key Laboratory of Modern Optical Instrumentations, Zhejiang University, Hangzhou 310058, China.
5. Department of Infectious Diseases, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.

✉ Corresponding authors: E-mail: zhoumedu.cn (MZ); 8xiedu.cn (Z.T); duzhen90edu.cn (Z.D); wangshoujieedu.cn (S.W)

Abstract

Rationale: Chronic wounds are one of the common complications of diabetes. Due to the physiological conditions of diabetic patients, these wounds are more susceptible to bacterial infections and the formation of bacterial biofilms, leading to the inefficiency of conventional antibiotic treatment.

Methods: Here, hollow mesoporous silica nanoparticles (HMSN) were used as the nanocarriers for co-delivery of azithromycin (AZM) and glucose oxidase (GOX), achieving a remarkable synergistic effect in chronic diabetic wounds. GOX possesses the catalytic ability to consume glucose and produce H₂O₂ in the diabetic wound area. The down-regulation of local glucose could effectively improve the chronic diabetic wound microenvironment. Meanwhile, the generated H₂O₂ effectively inhibits bacterial growth and eradicates bacterial biofilms with the synergism of antibiotics AZM.

Results: In the bacteria-infected diabetic cutaneous wound models, the reduction of glucose, generation of H₂O₂, and release of AZM could effectively reduce the bacterial infection and promote the wounds healing. Moreover, there is no obvious toxicity behavior after the treatment.

Conclusions: Therefore, the designed nanosystem could effectively accelerate the diabetic wound healing process by the amelioration of the hyperglycemia microenvironment and the eradication of bacterial biofilms around the wounds, making them promising candidates for clinical transformation.

Keywords: silica nanoparticle, glucose oxidase, azithromycin, bacterial biofilm, diabetic wound healing

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