Metal natural product complex Ru-procyanidins with quadruple enzymatic activity combat infections from drug-resistant bacteria  

作　　者：Jie Shan Xu Jin Cong Zhang Muchen Huang Jianghao Xing Qingrong Li Yuyu Cui Qiang Niu Xu Lin Chen Xianwen Wang 

机构地区：[1]Department of Burns,the First Affiliated Hospital of Anhui Medical University,Hefei 230022,China [2]School of Biomedical Engineering,Research and Engineering Center of Biomedical Materials,Anhui Provincial Institute of Translational Medicine,Anhui Medical University,Hefei 230032,China [3]Division of Gastroenterology,the First Affiliated Hospital of USTC,Division of Life Science and Medicine,University of Science and Technology of China,Hefei,Anhui 230026,China [4]The Second Clinical Medical College,Anhui Medical University,Hefei 230022,China [5]Department of Oncology,the First Affiliated Hospital of Anhui Medical University,Hefei 230022,China [6]College and Hospital of Stomatology,Anhui Medical University,Key Lab.of Oral Diseases Research of Anhui Province,Hefei 230032,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第5期2298-2316,共19页药学学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(52202343,82172204,82372552,82372517);Anhui Key Research and Development Plan(grant No.202104j07020027,China);Anhui Province Natural Science Foundation(2208085QC81,China);Research Fund of Anhui Institute of Translational Medicine(2022zhyx-C01,China);the Basic and Clinical Cooperative Research and Promotion Program of Anhui Medical University(2021xkjT028,China).The authors would like to thank the Shiyanjia lab(www.shiyanjia.com)for their help in language polishing.

摘　　要：Bacterial infection hampers wound repair by impeding the healing process.Concurrently,inflammation at the wound site triggers the production of reactive oxygen species(ROS),causing oxidative stress and damage to proteins and cells.This can lead to chronic wounds,posing severe risks.Therefore,eliminating bacterial infection and reducing ROS levels are crucial for effective wound healing.Nanozymes,possessing enzyme-like catalytic activity,can convert endogenous substances into highly toxic substances,such as ROS,to combat bacteria and biofilms without inducing drug resistance.However,the current nanozyme model with single enzyme activity falls short of meeting the complex requirements of antimicrobial therapy.Thus,developing nanozymes with multiple enzymatic activities is essential.Herein,we engineered a novel metalloenzyme called Ru-procyanidin nanoparticles(Ru-PC NPs)with diverse enzymatic activities to aid wound healing and combat bacterial infections.Under acidic conditions,due to their glutathione(GSH)depletion and peroxidase(POD)-like activity,Ru-PC NPs combined with H2O2 exhibit excellent antibacterial effects.However,in a neutral environment,the Ru-PC NPs,with catalase(CAT)activity,decompose H2O2 to O2,alleviating hypoxia and ensuring a sufficient oxygen supply.Furthermore,Ru-PC NPs possess exceptional antioxidant capacity through their superior superoxide dismutase(SOD)enzyme activity,effectively scavenging excess ROS and reactive nitrogen species(RNS)in a neutral environment.This maintains the balance of the antioxidant system and prevents inflammation.Ru-PC NPs also promote the polarization of macrophages from M1 to M2,facilitating wound healing.More importantly,Ru-PC NPs show good biosafety with negligible toxicity.In vivo wound infection models have confirmed the efficacy of Ru-PC NPs in inhibiting bacterial infection and promoting wound healing.The focus of this work highlights the quadruple enzymatic activity of Ru-PC NPs and its potential to reduce inflammation and promote bacteria-infected wound he

关 键 词：Nanozymes Quadruple enzymatic activity Antibacterial therapy Wound therapy RNA-seqAnti-inflammatory Reactive oxygen species Reactive nitrogen species 

分 类 号：R284.1[医药卫生—中药学]