Genetically Engineered Biomimetic Nanoparticles for Targeted Delivery of mRNA to Treat Rheumatoid Arthritis

• DOI: 10.1002/smtd.202300678
• Publication Date: 2023-08-01T12:10:45Z
• Authors: Jianhai Chen; Jianwei Tan; Jian Li; Wenxiang Cheng; Liqing Ke; Anqiao Wang; Qiqing Wang; Sien Lin; Gang Li; Benguo Wang; Jingqin Chen; Peng Zhang
• Keywords: Tensin

Abstract In addition to inhibiting persistent inflammation, phosphatase and tensin homolog deleted from chromosome 10 (PTEN) is known as an important therapeutic target for alleviating rheumatoid arthritis (RA) symptoms. Modulation of PTEN gene expression in synovial tissue using messenger RNA (mRNA) a promising approach combat RA. However, mRNA therapeutics are often hampered by unsatisfactory stability inefficient localization tissue. this study, genetically engineered biomimetic membrane‐coated (MR@P‐mPTEN) carrier that effectively delivers mRNA‐PTEN (mPTEN) directly the RA joint presented. By overexpressing tumor necrosis factor (TNF‐α) receptors on macrophage membranes via plasmid transfection, decoys reduce inflammatory pathway activation prepared TNF‐α. The resulting construct, MR@P‐mPTEN, shows good targeting based vivo fluorescence imaging. It also found MR@P‐mPTEN competitively binds TNF‐α activates vitro vivo, thereby synovitis damage. Clinical micro‐computed tomography histological analyses confirm treatment effects. These results suggest platform both inhibits pro‐inflammatory cytokines upregulates protein alleviate damage, providing new combination strategy treatment.