Journal
NANOSCALE
Volume 14, Issue 5, Pages 2052-2064Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/d1nr07611f
Keywords
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Funding
- National Natural Science Foundation of China [81961160736, 81801848]
- Sichuan Science and Technology Program [2021YJ0049, 2019YJ0141, 2019YFS0375]
- Chengdu International Science and Technology Cooperation Foundation [2020-GH03-00005-HZ, 2017-GH02-00025-HZ]
- State Key Laboratory of Polymer Materials Engineering [sklpme2019-2-05]
- Young Elite Scientist Sponsorship Program by CAST
- Youth Science and Technology Academic Leader Training Program of (SCU)
- Fundamental Research Funds for the Central Universities (SCU)
- Sichuan University-Luzhou City Special Funding for Strategic Cooperation [2020CDLZ-5]
- Experimental Technology Project of Sichuan University [SCU201207, SCU201204]
- Post-Doctor Research Project, West China Hospital, Sichuan University [2021HXBH033]
- Post-Doctor Research Project, Sichuan University [20826041E4084]
- Hong Kong Scholarship
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The innovative bimetal metal-organic framework domino micro-reactor generates a self-generating H2O2 microenvironment through a cascade reaction to effectively inhibit bacterial growth and achieve high-efficiency bactericidal performance. In vitro and in vivo studies demonstrate superior cytocompatibility, accelerating infectious full-thickness cutaneous regeneration through eradicating bacteria and promoting wound healing. The platform's advantage lies in blocking bacterial metabolism by starving them of energy, potentially preventing secondary infections.
Antibacterial chemodynamic therapy (aCDT) has captured considerable attention in the treatment of pathogen-induced infections due to its potential to inactivate bacteria through germicidal reactive oxygen species (ROS). However, the lifespan of ROS generated by CDT is too short to achieve the efficacy of complete sterilization; thus, residual bacteria inevitably reproduce and cause super-infections. To address this concern, we devise an innovative bimetal, metal-organic framework (BMOF) domino micro-reactor (BMOF-DMR), consisting of Cu/Zn-rich BMOF and glucose oxidase (GOx), via electrostatic self-assembly. GOx catalyzes conversion of glucose into H2O2, and the Cu2+ ions then convert H2O2 into OH to kill bacteria, thereby showing a domino effect. Accordingly, the BMOF-DMR not only blocks the nutrient/energy supply for bacteria, but also triggers a Fenton(-like) reaction and glutathione (GSH) depletion in a self-generating H2O2 microenvironment, all leading to high-efficiency bactericidal performance through synergistic starvation/chemodynamic therapy. Remarkably, in vitro and in vivo assessments demonstrate that the BMOF-DMR has superior cytocompatibility and exhibits robust ability to accelerate infectious full-thickness cutaneous regeneration through eradicating bacteria, promoting epithelialization of the wound beds and facilitating angiogenesis from the antibacterial activity and delivery of bimetal elements. The advantage of this antibacterial platform is that it suppresses bacterial metabolism by blocking the energy supply, which might prevent secondary infections from residual bacteria. As envisaged, the use of such a micro-reactor with starvation/chemodynamic therapy is a promising approach for combating bacterial skin wounds.
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