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

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

doi:10.1038/s41467-022-33492-6

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

Nat Commun. 2022 Oct 7;13(1):5925. doi: 10.1038/s41467-022-33492-6.

Authors

Hanyao Huang^#^{1

2

3}, Weiyi Pan^#^{1

4

5}, Yifan Wang^#^{6

7}, Hye Sung Kim^{2

8}, Dan Shao^{2

9}, Baoding Huang^{2

10}, Tzu-Chieh Ho², Yeh-Hsing Lao², Chai Hoon Quek², Jiayu Shi¹¹, Qianming Chen^{1

4

5}, Bing Shi^{1

3}, Shengmin Zhang¹², Lei Zhao^{13

14}, Kam W Leong^{15

16}

Affiliations

¹ State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China.
² Department of Biomedical Engineering, Columbia University, New York, 10027, NY, USA.
³ Department of Oral Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China.
⁴ Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China.
⁵ Stomatology Hospital, School of Stomatology, 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, Hangzhou, Zhejiang, 310016, China.
⁶ Advanced Biomaterials and Tissue Engineering Center and Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China.
⁷ School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
⁸ Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, the Republic of Korea.
⁹ Institutes for Life Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510006, China.
¹⁰ Department of Orthopaedic Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, Guangzhou, Guangdong, 510000, China.
¹¹ Department of Orthodontics and Pediatric Dentistry, School of Dentistry, The University of Michigan, Ann Arbor, 48109, MI, USA.
¹² Advanced Biomaterials and Tissue Engineering Center and Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China. smzhang@mail.hust.edu.cn.
¹³ State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China. jollyzldoc@163.com.
¹⁴ Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China. jollyzldoc@163.com.
¹⁵ Department of Biomedical Engineering, Columbia University, New York, 10027, NY, USA. kam.leong@columbia.edu.
¹⁶ Department of Systems Biology, Columbia University Medical Center, New York, 10032, NY, USA. kam.leong@columbia.edu.

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
Cell-Free Nucleic Acids* / genetics
Dendrimers* / pharmacology
Hydroxyapatites
Mice
Periodontitis* / drug therapy
Selenium*

Substances

Cell-Free Nucleic Acids
Dendrimers
Hydroxyapatites
Selenium