Infection associated with multidrug-resistant (MDR) bacteria has become a serious threat to public health, and there is an urgent demand of developing new antibiotics that offer combinatorial therapy to effectively combat MDR. Herein, a multifunctional two-dimensional nanoantibiotic was facilely designed and established on the basis of the covalent conjugation of CO-releasing molecule (CORM-401) and electrostatic adsorption of hyaluronic acid (HA) onto single-layered graphene quantum dots (SGQDs) to assemble SGQDs-CORM@HA nanosheets, abbreviated as SCH. Upon the enrichment of as-prepared nanoantibiotics in the community of targeted microbe, bacterial-secreted hyaluronidase (HAase) would cleave HA on SCH, and the sharp edges as well as the reactive sites on SGQDs-CORM nanosheets were exposed for cascade activation of synergistic antibacterial effects. Specifically, ultrathin SGQDs-CORM nanosheets can penetrate into bacterial cells deemed as the unique “nanoknife” effect. Under white light irradiation, SGQDs-CORM nanosheets can act as a high-efficient photosensitizer to generate cytotoxic singlet oxygen (¹O₂), as a well-recognized reactive oxygen species (ROS), to produce high oxidative stress and damage bacteria. As a complementary to photodynamic therapy (PDT), the accumulation of local ROS further triggered the release of CO to hinder the bacterial growth via causing plasma membrane damage and inducing metabolic disorders. Such synergistic treatment regimen arising from cascade-activated “nanoknife” effect and photodynamic/CO gas therapy, was devoted to outstanding on-demand antibacterial performance both in vitro and in vivo. Fascinatingly, the nanoplatform showed good biocompatibility toward both normal somatic cells and non-targeted bacteria. The remarkable antibacterial capability and admirable biocompatibility endow SCH with great potential to fight against MDR pathogens for in-coming clinical translations.

与多重耐药 (MDR) 细菌相关的感染已成为对公众健康的严重威胁，迫切需要开发新的抗生素来提供组合疗法以有效对抗 MDR。在此，基于CO释放分子（CORM-401）的共价结合和透明质酸（HA）在单层石墨烯量子点（SGQDs）上的静电吸附，设计并建立了一种多功能二维纳米抗生素。组装SGQDs-CORM@HA纳米片，缩写为SCH。在目标微生物群落中富集制备好的纳米抗生素后，细菌分泌的透明质酸酶 (HAase) 会在 SCH 上切割 HA，并且暴露了 SGQDs-CORM 纳米片上的尖锐边缘和反应位点，用于协同抗菌作用的级联激活。具体来说，超薄 SGQDs-CORM 纳米片可以渗透到细菌细胞中，被认为是独特的“纳米刀”效应。在白光照射下，SGQDs-CORM 纳米片可以作为高效光敏剂产生细胞毒性单线态氧。¹ O ₂ )，作为公认的活性氧 (ROS)，可产生高氧化应激和损伤细菌。作为光动力疗法（PDT）的补充，局部ROS的积累进一步触发CO的释放，通过引起质膜损伤和诱导代谢紊乱来阻碍细菌生长。这种由级联激活的“纳米刀”效应和光动力/CO 气体疗法产生的协同治疗方案，致力于在体外和体内具有出色的按需抗菌性能. 令人着迷的是，纳米平台对正常体细胞和非靶向细菌均表现出良好的生物相容性。卓越的抗菌能力和令人钦佩的生物相容性赋予 SCH 在即将到来的临床转化中对抗 MDR 病原体的巨大潜力。