Multifunctional nanozyme-reinforced copper-coordination polymer nanoparticles for drug-resistance bacteria extinction and diabetic wound healing

Jiahui Zhao; Tengfei Xu; Jichao Sun; Haitao Yuan; Mengyun Hou; Zhijie Li; Jigang Wang; Zhen Liang

doi:10.1186/s40824-023-00429-z

Multifunctional nanozyme-reinforced copper-coordination polymer nanoparticles for drug-resistance bacteria extinction and diabetic wound healing

Biomater Res. 2023 Sep 18;27(1):88. doi: 10.1186/s40824-023-00429-z.

Authors

Jiahui Zhao^#^{1

2}, Tengfei Xu^#^{1

3}, Jichao Sun¹, Haitao Yuan^{1

2}, Mengyun Hou¹, Zhijie Li⁴, Jigang Wang^{5

6}, Zhen Liang⁷

Affiliations

¹ Department of Geriatrics and Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, 518020, P. R. China.
² Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, P. R. China.
³ College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
⁴ Department of Geriatrics and Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, 518020, P. R. China. li.zhijie@szhospital.com.
⁵ Department of Geriatrics and Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, 518020, P. R. China. jgwang@icmm.ac.cn.
⁶ State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China. jgwang@icmm.ac.cn.
⁷ Department of Geriatrics and Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, 518020, P. R. China. Liang.zhen@szhospital.com.

^# Contributed equally.

Abstract

Background: Drug-resistant bacterial infections in chronic wounds are a persistent issue, as they are resistant to antibiotics and can cause excessive inflammation due to generation of reactive oxygen species (ROS). An effective solution would be to not only combat bacterial infections but also scavenge ROS to relieve inflammation at the wound site. Scaffolds with antioxidant properties are attractive for their ability to scavenge ROS, and there is medical demand in developing antioxidant enzyme-mimicking nanomaterials for wound healing.

Methods: In this study, we fabricated copper-coordination polymer nanoparticles (Cu-CPNs) through a self-assembly process. Furthermore, ε-polylysine (EPL), an antibacterial and cationic polymer, was integrated into the Cu-CPNs structure through a simple one-pot self-assembly process without sacrificing the glutathione peroxidase (GPx) and superoxide dismutase (SOD)-mimicking activity of Cu-CPNs.

Results: The resulting Cu-CPNs exhibit excellent antioxidant propertiesin mimicking the activity of glutathione peroxidase and superoxide dismutase and allowing them to effectively scavenge harmful ROS produced in wound sites. The in vitro experiments showed that the resulting Cu-CPNs@EPL complex have superior antioxidant properties and antibacterial effects. Bacterial metabolic analysis revealed that the complex mainly affects the cell membrane integrity and nucleic acid synthesis that leads to bacterial death.

Conclusions: The Cu-CPNs@EPL complex has impressive antioxidant properties and antibacterial effects, making it a promising solution for treating drug-resistant bacterial infections in chronic wounds. The complex's ability to neutralize multiple ROS and reduce ROS-induced inflammation can help relieve inflammation at the wound site. Schematic illustration of the ROS scavenging and bacteriostatic function induced by Cu-CPNs@EPL nanozyme in the treatment of MRSA-infected wounds.

Keywords: Anti-bacteria; Anti-inflammation; Copper-coordination polymer nanoparticles; Nanozyme; Reactive oxygen species.

Abstract

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