Yulan Zhao, Quan Xu, Shijie Zheng, Yi Liu, Zhiyong Song, Heyou Han
Drug-resistant bacterial infections rank among the most critical public health threats across the globe. The development of novel antibiotics falls considerably behind the rise of bacterial resistance. The advancement of nanotechnology offers novel opportunities to address the challenges posed by drug-resistant bacterial infections. In recent years, copper-based nanomaterials have gained widespread application in chemodynamic therapy (CDT) due to their favorable nanoenzymatic activities. However, their therapeutic efficacy is seriously constrained by the insufficient H2O2 supply and overexpressed glutathione (GSH) within the infected wound microenvironment. Therefore, a H2O2 self-supplying and GSH-depleting nanosystem (CuO2@ZIF-8) was rationally constructed by simply encapsulating copper peroxide (CuO2) within a zeolitic imidazolate framework-8 (ZIF-8). Under the acidic microenvironment of the infection sites, ZIF-8 underwent degradation to liberate Zn2+ ions, which exhibited potent antibacterial activity. Meanwhile, after being degraded, ZIF-8 released CuO2, which in the slightly acidic infected microenvironment decomposed to generate H2O2 and Cu2+. The released Cu2+ then catalyzed the H2O2 into highly toxic hydroxyl radicals (·OH), thus achieving a great antibacterial effect between CDT and Zn2+. In addition, Cu2+ could be reduced to Cu+ by the overexpressed GSH, further enhancing the efficacy of CDT. In vitro antibacterial assay showed that due to the antibacterial effect of CDT and Zn2+, the antibacterial rate of CuO2 @ ZIF-8 reached as high as 98.8%, which was significantly superior to that of ZIF-8 or CuO2 used alone. In vivo assay showed that CuO2 @ ZIF-8 had good antibacterial effects and excellent wound healing with great in vivo biosafety. In conclusion, the CuO2 @ ZIF-8 nanoplatform developed in this work has considerable promise for future biomedical applications.