Periodontitis doctor-worker cross-sulfated chitosan modified CuS nanoclusters: a multifunctional nano-preparation for simultaneous antibacterial and bone regeneration treatment of periodontitis Periodontitis is a chronic inflammatory disease worldwide, which is caused by periodontal pathogens and leads to the progressive destruction of periodontal tissue, especially alveolar bone. In order to effectively solve periodontitis, a nano-preparation called CuS@MSN-SCS was proposed in this study. The formula includes coating citrate-grafted copper sulfide (CuS) nanoparticles with mesoporous silica (MSN), and then surface modification with amino groups and sulfated chitosan (SCS) through electrostatic interaction. The purpose of this formula is to achieve effective bacterial removal by inducing Cu 2+ ion-mediated ROS signaling pathway. In addition, it aims to promote alveolar bone regeneration through Cu 2+-induced angiogenesis and SCS-mediated bone regeneration. As expected, the negatively charged CuS nanoparticles capped by sodium citrate were successfully coated by MSN by adjusting the surface charge, and then (3- aminopropyl) triethoxysilane was used to introduce amino groups, and then SCS was introduced by electrostatic interaction, resulting in the formation of CuS@MSN-SCS. It was verified that the nano-preparation not only significantly aggravated the oxidative stress of Fusobacterium nucleatum in vitro, thus inhibiting bacterial growth and biofilm formation, but also effectively reduced inflammatory reaction and promoted alveolar bone regeneration in rat periodontitis model in vivo, and had no obvious biological toxicity. These findings contribute to the therapeutic effect of periodontitis. Overall, this study successfully developed a nano-preparation for fighting bacteria and promoting alveolar bone regeneration, which showed great potential for clinical treatment of periodontitis. Innovations: 1. Multi-functional nano-platform integration: integrating antibacterial, anti-inflammatory and bone regeneration functions into a single nano-preparation for the first time to realize a comprehensive solution for periodontitis treatment; 2. Precise control of surface modification: through electrostatic interaction and fine surface engineering, the precise functionalization of nanoparticles is successfully realized, and the surface charge and biological function are controlled; 3. Intelligent regulation of Cu2+ ions: The synergistic effect of treatment is realized by using the dual action mechanism of Cu2+ions, simultaneously inducing bacterial oxidative stress and promoting angiogenesis; 4. mesoporous silica carrier innovation: mesoporous silica is used as the carrier platform to provide excellent dispersion and functional modification space. Scientific research inspiration: 1. We can explore the ROS signaling pathway mediated by other metal ions; 2. To study the influence of different proportions of formula on the therapeutic effect; 3. Investigate the long-term stability and storage conditions of nano-preparations; 4. Explore other surface modification methods to further optimize the performance. Extension of ideas: 1. The design idea of multifunctional materials can be used for the treatment of other diseases; 2. The surface charge control strategy can be applied to the preparation of other nanomaterials; 3. The electrostatic assembly method provides a new idea for the development of nano-drugs; 4. The study of 4.ROS signaling pathway is of great significance for understanding the therapeutic mechanism; 5. The biocompatibility evaluation system can be used for reference in other nanomaterials; 6. Synergetic therapy strategy is worth popularizing in the treatment of other diseases; 7. The characterization method of nano-materials has reference value for related research. Similar research ideas: 1. Metal-organic skeleton nanoparticles are used to enhance antibacterial and bone regeneration capabilities through surface modification. 2. Develop nanoparticles based on bioceramics, load antibacterial drugs and growth factors, and realize synergistic therapy. 3. Develop injectable degradable hydrogel with antibacterial and bone regeneration functions. 4. Using extracellular exosomes as natural nano-carriers, loading antibacterial peptides and bone regeneration factors. 5. Develop nano-materials treated by plasma, endow them with antibacterial properties and promote bone regeneration through surface modification. DOI : 10.1021/acsnano.4c00137