Targeting Nanotherapeutics for Highly Efficient Diagnosis and Treatment of Systemic Lupus Erythematosus through Regulation of Immune Response.

Abstract

Systemic lupus erythematosus (SLE) is characterized by the production of pathogenic autoantibodies, particularly antidouble-stranded (ds) DNA antibodies, which contribute to multiorgan damage (lupus nephritis, LN). Hence, there is an urgent need to recognize and eliminate SLE-specific anti-ds DNA antibodies to enhance the SLE treatment. Herein, mesoporous silica (MSNs) loaded with SeC and surface-modified ctDNA are constructed to effectively specific bind and eliminate pathogenic anti-dsDNA antibodies for treatment SLE in 125 plasm and enabling swift LN diagnosis in 36 kidney tissue from SLE patients. As expected, the clearance ratio of anti-dsDNA antibodies by nanotherapeutics is significantly greater compared to other products commonly used in clinical therapies and exhibits biocompatibility and safety in patients. Moreover, MSNs-DNA can also help visualize the distribution of anti-dsDNA antibodies in the lesions of the kidney. Importantly, the combination strategy (MSNs-DNA@SeC) can effectively remove antibodies and reduce UP production by the regulation of B cells and T cells in female MRL/lpr SLE model mice to alleviate related symptoms. Collectively, the resultant data not only presents a straightforward method for the systematic design of nanomedicine targeting SLE to enhance the effects on diagnosis and treatment, but also elucidates the potential mechanisms involving anti-dsDNA antibodies in the pathogenesis and progression of SLE.