Nanoparticulate cell-free DNA scavenger for treating inflammatory bone loss in periodontitis

作者：Huang, Hanyao; Pan, Weiyi; Wang, Yifan; Kim, Hye Sung; Shao, Dan; Huang, Baoding; Ho, Tzu-Chieh; Lao, Yeh-Hsing; Quek, Chai Hoon; Shi, Jiayu; Chen, Qianming; Shi, Bing; Zhang, Shengmin^*; Zhao, Lei^*; Leong, Kam W.^*

来源：Nature Communications, 2022, 13(1): 5925.

DOI：10.1038/s41467-022-33492-6

• ORAL BACTERIA
• RECEPTOR 9
• SELENIUM
• CANCER
• TLR9
• EXPRESSION
• APOPTOSIS
• RESPONSES
• BINDING
• PLASMA

Periodontitis is a common type of inflammatory bone loss and a risk factor for systemic diseases. The pathogenesis of periodontitis involves inflammatory dysregulation, which represents a target for new therapeutic strategies to treat periodontitis. After establishing the correlation of cell-free DNA (cfDNA) level with periodontitis in patient samples, we test the hypothesis that the cfDNA-scavenging approach will benefit periodontitis treatment. We create a nanoparticulate cfDNA scavenger specific for periodontitis by coating selenium-doped hydroxyapatite nanoparticles (SeHANs) with cationic polyamidoamine dendrimers (PAMAM-G3), namely G3@SeHANs, and compare the activities of G3@SeHANs with those of soluble PAMAM-G3 polymer. Both G3@SeHANs and PAMAM-G3 inhibit periodontitis-related proinflammation in vitro by scavenging cfDNA and alleviate inflammatory bone loss in a mouse model of ligature-induced periodontitis. G3@SeHANs also regulate the mononuclear phagocyte system in a periodontitis environment, promoting the M2 over the M1 macrophage phenotype. G3@SeHANs show greater therapeutic effects than PAMAM-G3 in reducing proinflammation and alveolar bone loss in vivo. Our findings demonstrate the importance of cfDNA in periodontitis and the potential for using hydroxyapatite-based nanoparticulate cfDNA scavengers to ameliorate periodontitis.

• 单位
  华中科技大学; 中山大学; 6; 浙江大学; 四川大学