Advances in nanodelivery systems based on apoptosis strategies for enhanced rheumatoid arthritis therapy

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder primarily characterized by persistent synovial inflammation and progressive bone erosion. The pathogenesis of RA involves a complex cascade of cellular and molecular events, including sustained hyperactivation of macrophages, excessive recruitment and activation of neutrophils, pathological proliferation and invasion of fibroblast-like synoviocytes (FLS), and dysregulated differentiation and function of osteoclasts (OCs). The inflammatory factors secreted by these dysregulated cells significantly disrupt the joint microenvironment through multiple pathological mechanisms, primarily by promoting synovial inflammation, cartilage matrix degradation, osteoclast-mediated bone erosion, and pathological angiogenesis. Therapeutic strategies targeting the induction of apoptosis in these malignant cells have demonstrated considerable potential in preclinical studies, offering a promising approach to enhance treatment outcomes by simultaneously reducing inflammatory cytokine production and inhibiting pathogenic cell proliferation. However, conventional therapeutic drugs are limited in clinical applications because of their high toxicity and side effects. Inflammation induces morphological and functional changes in cells within the rheumatoid arthritis microenvironment (RAM), particularly the overexpression of specific receptors on cell membranes. This phenomenon has driven the development of ligand-modified targeted nanodelivery systems (NDSs), which can specifically target and induce apoptosis in specific cell types, thereby enhancing therapeutic efficacy. This paper comprehensively reviews the research progress of targeted NDSs based on apoptosis strategies for RA therapy, with a detailed discussion of their advantages in inducing apoptosis in various disease-associated cells. Furthermore, the potential of combining apoptosis of multiple cell types for RA treatment is explored. This review is expected to improve insights into the apoptosis of malignant cells to enhance RA therapy. STATEMENT OF SIGNIFICANCE: This review highlights recent advances in nanodelivery systems (NDSs) based on apoptotic strategies for enhanced rheumatoid arthritis (RA) therapy. Unlike conventional NDSs, these optimized systems specifically induce apoptosis in malignant cells within the RA microenvironment by integrating multiple therapeutic strategies. By summarizing the latest research, our work demonstrates the potential of these NDSs to suppress inflammatory responses and prevent bone destruction through targeted elimination of malignant cells, offering a novel direction for RA treatment. This review is significant as it provides a comprehensive overview for researchers and clinicians, facilitating the development of more effective therapeutic approaches for RA and other chronic inflammatory diseases.