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

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

Nature communications (2022-10-08)
Hanyao Huang, Weiyi Pan, Yifan Wang, Hye Sung Kim, Dan Shao, Baoding Huang, Tzu-Chieh Ho, Yeh-Hsing Lao, Chai Hoon Quek, Jiayu Shi, Qianming Chen, Bing Shi, Shengmin Zhang, Lei Zhao, Kam W Leong
摘要

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.

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Anti-TLR9 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution