A multifunctional nanodrug, PAMAM@CuS-HA-RB/DOX, was prepared for the real time tracking and chemo-photothermal therapy of tumor cells. The CuS nanoclusters with diameter less than 10 nm could be easily ingested by tumor cells and showed good colloid stability and high photothermal conversion efficiency. The hyaluronic acid (HA) coating and rhodamine B (RB) labeling endowed the nanocomposite with low cytotoxity and real time fluorescence imaging ability. In the acidic tumor microenvironment, the doxorubicin linked via the pH-responsive hydrazone bonds was released and worked synergistically with CuS to kill the tumor cells, which showed a high chemo-photothermal therapy capacity. All these properties indicated the PAMAM@CuS-HA-RB/DOX have promising application for the therapy of cancers and tracking of nanodrugs.
Periodontitis, a prevalent chronic inflammatory disease worldwide, is triggered by periodontopathogenic bacteria, resulting in the progressive destruction of periodontal tissue, particularly the alveolar bone. To effectively address periodontitis, this study proposed a nanoformulation known as CuS@MSN-SCS. This formulation involves coating citrate-grafted copper sulfide (CuS) nanoparticles with mesoporous silica (MSNs), followed by surface modification using amino groups and sulfated chitosan (SCS) through electrostatic interactions. The objective of this formulation is to achieve efficient bacteria removal by inducing ROS signaling pathways mediated by Cu2+ ions. Additionally, it aims to promote alveolar bone regeneration through Cu2+-induced pro-angiogenesis and SCS-mediated bone regeneration. As anticipated, by regulating the surface charges, the negatively charged CuS nanoparticles capped with sodium citrate were successfully coated with MSNs, and the subsequent introduction of amine groups using (3-aminopropyl)triethoxysilane was followed by the incorporation of SCS through electrostatic interactions, resulting in the formation of CuS@MSN-SCS. The developed nanoformulation was verified to not only significantly exacerbate the oxidative stress of Fusobacterium nucleatum, thereby suppressing bacteria growth and biofilm formation in vitro, but also effectively alleviate the inflammatory response and promote alveolar bone regeneration without evident biotoxicity in an in vivo rat periodontitis model. These findings contribute to the therapeutic effect on periodontitis. Overall, this study successfully developed a nanoformulation for combating bacteria and facilitating alveolar bone regeneration, demonstrating the promising potential for clinical treatment of periodontitis.
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