Sprayed copper peroxide nanodots for accelerating wound healing in a multidrug-resistant bacteria infected diabetic
Ran Zhang1, Guhua Jiang1, Qianqian Gao2
1Department of Preventive Medicine and Public Health Laboratory Science, School of Medicine, Jiangsu University, Zhenjiang 212013, China. shenhj@ujs.edu.cn.
Abstract:
Vascular dysfunction and bacterial infection are key factors for the non-healing of diabetic ulcers. Growth factors and antibiotics seem to effectively target both issues. However, the short half-life and high cost of growth factors and the antibiotics resistance of bacteria greatly limit their further widespread applications. Novel strategies or agents with both angiogenic and antibacterial activities are urgently desirable. Copper peroxide (CuO2) nanodots were reported to be decomposed into Cu2+ and H2O2 under mild acid conditions (pH 5.5). Considering that both decomposed products are acknowledged antibacterial agents (Cu2+, H2O2) and angiogenesis activator (Cu2+), we believe that CuO2 nanodots are suitable for diabetic ulcer treatment because the pathological environment of infected chronic wounds is mildly acidic with pH 5.5-5.6. As expected, in vitro experiments showed that CuO2 nanodots possessed excellent bactericidal properties against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and even methicillin-resistant Staphylococcus aureus (MRSA). CuO2 nanodots induced the high expression of hypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF) in human umbilical vein endothelial cells (HUVECs), subsequently promoting the cell migration and tube formation for angiogenesis. In particular, CuO2 nanodots exhibited good dispersibility and sprayable behavior in water. In vivo experiments demonstrated that the spayed CuO2 nanodots in the wound area could effectively combat MRSA, reduce inflammation, promote angiogenesis, and consequently accelerate wound healing. Moreover, the sprayed CuO2 nanodots in the wound sites caused negligible system toxicity. This study provides proof-of-principle evidence for applying the sprayed CuO2 nanodots for infected diabetic ulcer treatment.
Insights
Copper peroxide (CuO2) nanodots effectively treat diabetic ulcers by killing bacteria and promoting blood vessel growth. These sprayable nanodots offer a promising solution for infected wounds with minimal toxicity.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Wound Healing
Background:
- Diabetic ulcers often fail to heal due to vascular dysfunction and bacterial infections.
- Current treatments like growth factors and antibiotics have limitations such as short half-lives, high costs, and antibiotic resistance.
- Novel agents with combined angiogenic and antibacterial properties are needed for effective diabetic ulcer treatment.
Purpose of the Study:
- To investigate the potential of copper peroxide (CuO2) nanodots as a therapeutic agent for infected diabetic ulcers.
- To evaluate the antibacterial and angiogenic activities of CuO2 nanodots.
- To assess the efficacy and safety of sprayable CuO2 nanodots in a preclinical setting.
Main Methods:
- CuO2 nanodots were synthesized and characterized.
- In vitro antibacterial activity was tested against various bacterial strains, including MRSA.
- In vitro angiogenic potential was assessed by measuring HIF-1α and VEGF expression in HUVECs, and evaluating cell migration and tube formation.
- In vivo efficacy was evaluated in a mouse model of infected diabetic ulcers, assessing bacterial load, inflammation, angiogenesis, and wound healing.
- Systemic toxicity was also evaluated.
Main Results:
- CuO2 nanodots demonstrated potent bactericidal effects against E. coli, S. aureus, P. aeruginosa, and MRSA in vitro.
- CuO2 nanodots significantly induced HIF-1α and VEGF expression in HUVECs, promoting angiogenesis.
- In vivo studies showed that sprayed CuO2 nanodots effectively reduced MRSA burden, decreased inflammation, enhanced angiogenesis, and accelerated wound healing.
- The treatment exhibited negligible systemic toxicity.
Conclusions:
- CuO2 nanodots possess dual antibacterial and angiogenic properties, making them suitable for treating infected diabetic ulcers.
- Sprayable CuO2 nanodots offer a convenient and effective therapeutic strategy for promoting diabetic ulcer healing.
- This study provides strong evidence for the clinical potential of CuO2 nanodots in managing complex wound infections.
