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.