4.8 Article

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

Journal

THERANOSTICS
Volume 12, Issue 6, Pages 2658-2673

Publisher

IVYSPRING INT PUBL
DOI: 10.7150/thno.64244

Keywords

silica nanoparticle; glucose oxidase; azithromycin; bacterial biofilm; diabetic wound healing

Funding

  1. National Natural Science Foundation of China [81971667]
  2. Key Research and Development Project of Zhejiang Province [2020C03035]
  3. Fundamental Research Funds for the Zhejiang Provincial Universities [2021XZZX034]

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The study used hollow mesoporous silica nanoparticles to deliver azithromycin and glucose oxidase, achieving a significant synergistic effect in chronic diabetic wounds. This method promotes wound healing by improving the wound microenvironment and eradicating bacterial biofilms.
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.

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