Ma Guoxin, Xu Ke, Yu Leixiao, Haag Rainer
Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, Berlin, 14195, Germany.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610064, China.
Angew Chem Int Ed Engl. 2025 Feb 24;64(9):e202418882. doi: 10.1002/anie.202418882. Epub 2025 Feb 3.
Periodontitis is a microbe-driven inflammatory disease leading to bone resorption and tissue destruction. We propose a dual-functional nanogel complex armed with the antimicrobial drug triclosan (TCS) and the pro-angiogenesis medication deferoxamine (DFO) for combating microbial pathogens and promoting tissue regeneration. The nanogel system (NG-TCS-DFO) that we fabricated from linear polyglycerol exhibits well-defined spherical morphology and a positively charged surface for bacteria adhesion. The rapid and sustained degradation of NG-TCS-DFO in the acidic environment of an infection site induces the on-demand release of TCS and DFO. The NG-TCS-DFO shows potent bacteria elimination of the gingivitis-causing bacteria Porphyromonas gingivalis in both planktonic (99.9 %) and biofilm (99 %) states. Furthermore, the NG-TCS-DFO can promote vascularization and migration of human umbilical vein endothelial cells (HUVECs). Contributing to the synergistic effect of TCS and DFO, the NG-TCS-DFO demonstrates significant bone tissue regeneration and accelerated healing of periodontitis in vivo. This polyglycerol-based nanogel may therefore offer smart combined delivery of multiple therapeutics against bacteria-driven diseases.
牙周炎是一种由微生物驱动的炎症性疾病，可导致骨吸收和组织破坏。我们提出了一种双功能纳米凝胶复合物，其负载抗菌药物三氯生（TCS）和促血管生成药物去铁胺（DFO），用于对抗微生物病原体并促进组织再生。我们用线性聚甘油制备的纳米凝胶系统（NG-TCS-DFO）呈现出明确的球形形态和带正电荷的表面，有利于细菌黏附。NG-TCS-DFO在感染部位的酸性环境中快速且持续降解，可诱导TCS和DFO按需释放。NG-TCS-DFO对引起牙龈炎的牙龈卟啉单胞菌在浮游状态（99.9%）和生物膜状态（99%）下均显示出强大的杀菌能力。此外，NG-TCS-DFO可促进人脐静脉内皮细胞（HUVECs）的血管生成和迁移。得益于TCS和DFO的协同作用，NG-TCS-DFO在体内显示出显著的骨组织再生能力，并加速了牙周炎的愈合。因此，这种基于聚甘油的纳米凝胶可能为对抗细菌驱动的疾病提供多种治疗药物的智能联合递送。
