Cationic brush hybrid nanoparticles scavenge cell-free DNA to enhance rheumatoid arthritis treatment

Xingliang Liu; Shi Chen; Lixin Liu; Yongming Chen

doi:10.1016/j.actbio.2023.08.032

Cationic brush hybrid nanoparticles scavenge cell-free DNA to enhance rheumatoid arthritis treatment

Acta Biomater. 2023 Oct 15:170:215-227. doi: 10.1016/j.actbio.2023.08.032. Epub 2023 Aug 23.

Authors

Xingliang Liu¹, Shi Chen¹, Lixin Liu², Yongming Chen³

Affiliations

¹ School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-sen University, Guangzhou 510275, China.
² School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-sen University, Guangzhou 510275, China; State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China. Electronic address: liulixin@mail.sysu.edu.cn.
³ School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-sen University, Guangzhou 510275, China; Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China; State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China. Electronic address: chenym35@mail.sysu.edu.cn.

PMID: 37619897
DOI: 10.1016/j.actbio.2023.08.032

Abstract

Abnormally high level of cell-free DNA (cfDNA) is one of the important causes of autoimmune diseases, which aggravate the symptoms of rheumatoid arthritis (RA). Recently, the utilization of cationic polymeric nanoparticles for scavenging cfDNA has emerged as a promising therapeutic strategy for the treatment of RA. However, the intravenous introduction of cationic polymeric nanoparticles into the circulation carries a risk of dissociation, causing toxicity. To realize the potential clinical translation, we employed a series of silica particles grafted with poly(2-(dimethylamino) ethyl methacrylate) (PDMA) (SiNP@PDMA) brush, which possess adjustable PDMA content (100, 200, and 300 degree of polymerization (DP)) and particle size (50, 100, and 200 nm diameter), to selectively scavenge cfDNA in inflamed joint cavity. We demonstrate that the binding affinity for cfDNA, cytotoxicity, circulation time in vivo and retention in the inflamed joint cavity are influenced by the core-shell structure of SiNP@PDMA, ultimately impacting therapeutic efficacy. Among them, SiNP@PDMA with 100 nm size and 200 DP of PDMA exhibit enhanced accumulation and prolonged retention time in inflammatory joint cavity, resulting in superior therapeutic effect. Therefore, in this study, applying the precisely tuning size and cation content of SiNP@PDMA, we demonstrated the factors to matter the therapeutic effect of cationic nanoparticles, which deepened the understanding of the anti-inflammatory therapies based on cfDNA scavenger for RA. STATEMENT OF SIGNIFICANCE: Inspired by the discovery that cfDNA would induce inappropriate immune responses to exacerbate the progress of RA, we innovatively employed SiNP@PDMA as a cfDNA scavenger to inhibit cfDNA-induced inflammation in RA. Increase in the cation content efficiently strengthened the binding between SiNP@PDMA and cfDNA, leading to an improvement in inhibitory effect of inflammation. In addition, we compared the behaviors of 50, 100 and 200 nm SiNP@PDMA in RA symptom suppression, local cfDNA scavenging and inflammation inhibition. The results demonstrated that SiNP₁₀₀-PDMA₂₀₀ outperformed other analogues, corresponding to their more favorable distribution in inflammatory articular cavity. Together, this study revealed the structure-property relationship of cfDNA scavengers for further development of safe and effective cfDNA scavenging system.

Keywords: Cationic nanoparticle; Cell free DNA; Inflammation; Rheumatoid arthritis.