Dimethylamino group modified polydopamine nanoparticles with positive charges to scavenge cell-free DNA for rheumatoid arthritis therapy

Ying Chen; Yonglin Wang; Xianfang Jiang; Jinhong Cai; Yuting Chen; Hanji Huang; Yuan Yang; Li Zheng; Jinmin Zhao; Ming Gao

doi:10.1016/j.bioactmat.2022.03.028

Dimethylamino group modified polydopamine nanoparticles with positive charges to scavenge cell-free DNA for rheumatoid arthritis therapy

Bioact Mater. 2022 Mar 28:18:409-420. doi: 10.1016/j.bioactmat.2022.03.028. eCollection 2022 Dec.

Authors

Ying Chen^{1

2}, Yonglin Wang^{1

3}, Xianfang Jiang^{1

4}, Jinhong Cai^{1

2}, Yuting Chen^{1

2

3}, Hanji Huang^{1

2}, Yuan Yang^{1

2

3

5}, Li Zheng^{1

2

5}, Jinmin Zhao^{1

2

3

5}, Ming Gao^{1

2}

Affiliations

¹ Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.
² Guangxi Collaborative Innovation Center of Regenerative Medicine and Medical Bioresource Development and Application, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.
³ Department of Orthopedics, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.
⁴ Department of Oral Radiology, College of Stomatology of Guangxi Medical University, Nanning, 530021, China.
⁵ Guangxi Key Laboratory of Regenerative Medicine, International Joint Laboratory on Regeneration of Bone and Soft Tissues, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.

Abstract

Excessive cell-free DNA (cfDNA) released by damaged or apoptotic cells can cause inflammation, impacting the progression of rheumatoid arthritis (RA). cfDNA scavengers, such as cationic nanoparticles (NPs), have been demonstrated as an efficient strategy for treating RA. However, most scavengers are limited by unfavorable biocompatibility and poor scavenging efficacy. Herein, by exploiting the favorable biocompatibility, biodegradability and bioadhesion of polydopamine (P), we modified P with dimethylamino groups to form altered charged DPs to bind negatively charged cfDNA for RA therapy. Results showed that DPs endowed with superior binding affinity of cfDNA and little cytotoxicity, which effectively inhibited lipopolysaccharide (LPS) stimulated inflammation in vitro, resulting in the relief of joint swelling, synovial hyperplasia and cartilage destruction in RA rats. Significantly, DPs with higher DS of bis dimethylamino group exhibited higher positive charge density and stronger cfDNA binding affinity, leading to excellent RA therapeutic effect among all of the treated groups, which was even close to normal rats. These finding provides a novel strategy for the treatment of cfDNA-associated diseases.

Keywords: Cell-free DNA; Immunotherapy; Nucleic acid binding affinity; Polydopamine; Rheumatoid arthritis.