Intracellular carbon monoxide release unveils selective antibacterial effects  

胞内一氧化碳释放揭示其选择性抗菌作用

作　　者：Tengfei Ma Shaoqiu Zheng Jian Cheng Guoying Zhang Jinming Hu 马腾飞;郑少秋;程健;张国颖;胡进明

机构地区：[1]Department of Pharmacy,The First Affiliated Hospital of University of Science and Technology of China(USTC),Hefei 230026,China [2]Key Laboratory of Precision and Intelligent Chemistry,Department of Polymer Science and Engineering,University of Science and Technology of China,Hefei 230026,China

出　　处：《Science China Materials》2024年第12期3849-3860,共12页中国科学（材料科学）（英文版）

基　　金：supported by the National Natural Scientific Foundation of China(52350348,52233009,52021002,92356302,52273155,and 52073270);the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0450301 and XDB0450102);the CAS Project for Young Scientists in Basic Research(YSBR-094);the Joint Funds from Hefei National Synchrotron Radiation Laboratory(KY2060000197);the Collaborative Innovation Program of Hefei Science Center,CAS(2022HSC-CIP012)。

摘　　要：Carbon monoxide(CO)is recognized as a diffusible and biologically membrane-permeable gasotransmitter.However,the question of whether extracellular and intracellular CO delivery would yield similar or distinct biological functions remains unresolved.In this study,utilizing nonmetallic CO-releasing micelles as a platform for localized CO delivery,we present evidence suggesting that selective antibacterial effects against Staphylococcus aureus(S.aureus)are exclusively evident upon intracellular CO release,even in cases of extracellular release with higher CO concentrations showing no comparable effect.To substantiate this assertion,we systematically design micellar nanoparticles with varying sizes,monomer sequences,and shell compositions.Among these variants,only the micelles taken up by S.aureus and capable of intracellular CO release exhibit efficient bacteria-killing properties.We further demonstrate that the selective bactericidal effect is closely linked to the production of hydroxyl radicals after intracellular CO release.Additionally,intracellular CO release proves to be an efficient treatment for S.aureus-induced skin abscesses without the need for additional antibiotics,showcasing synergistic antibacterial and anti-inflammatory effects.These findings underscore the pivotal role of the spatial location of CO release,significantly enhancing our understanding of the pathophysiological functions of gasotransmitters.一氧化碳(CO)是一种具有扩散性和生物膜渗透性的气体递质.然而,细胞外和细胞内的共同递送是否会产生相似或不同的生物功能的问题仍然没有解决.本研究中,我们利用非金属共释放胶束作为局部CO递送的平台,系统地设计了不同尺寸、单体序列和壳层的胶束纳米颗粒.在上述胶束中,只有被金黄色葡萄球菌(S.aureus)摄取并能够在细胞内共释放的胶束表现出有效的杀菌特性.我们进一步证明,选择性杀菌作用与细胞内CO释放后羟基自由基的产生密切相关.此外,细胞内CO释放被证明可以有效治疗S.aureus引起的皮肤脓肿,且不需要额外的抗生素,显示出协同抗菌和抗炎作用.本研究证实了CO释放的空间位置对其抗菌性能具有重要影响,深化了对气体递质生理功能的理解和认识.

关 键 词：carbon monoxide intracellular release ANTIBACTERIAL ANTI-INFLAMMATION cutaneous abscesses 

分 类 号：R318[医药卫生—生物医学工程]