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

Author

Listed:
  • Hanyao Huang

    (Sichuan University
    Columbia University
    Sichuan University)

  • Weiyi Pan

    (Sichuan University
    Sichuan University
    Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University)

  • Yifan Wang

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Hye Sung Kim

    (Columbia University
    Dankook University)

  • Dan Shao

    (Columbia University
    South China University of Technology)

  • Baoding Huang

    (Columbia University
    Sun Yat-sen University and Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology)

  • Tzu-Chieh Ho

    (Columbia University)

  • Yeh-Hsing Lao

    (Columbia University)

  • Chai Hoon Quek

    (Columbia University)

  • Jiayu Shi

    (The University of Michigan)

  • Qianming Chen

    (Sichuan University
    Sichuan University
    Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University)

  • Bing Shi

    (Sichuan University
    Sichuan University)

  • Shengmin Zhang

    (Huazhong University of Science and Technology)

  • Lei Zhao

    (Sichuan University
    Sichuan University)

  • Kam W. Leong

    (Columbia University
    Columbia University Medical Center)

Abstract

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.

Suggested Citation

  • 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, 2022. "Nanoparticulate cell-free DNA scavenger for treating inflammatory bone loss in periodontitis," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33492-6
    DOI: 10.1038/s41467-022-33492-6
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