Specific nanotherapeutics for highly efficient diagnosis and treatment of systemic lupus erythematosus

Abstract Systemic lupus erythematosus (SLE) with increasing morbidity and mortality rate is characterized by multisystem damage and diverse autoantibodies production, such as anti-double stranded (ds) DNA antibodies. It is noted that anti-dsDNA antibodies are essential in the pathogenesis and progression of SLE and lupus nephritis (LN), however; anti-dsDNA antibodies could not be specifically recognized and quickly removed in clinic. Therefore, it is urgently needed to develop SLE-specific targeting agents to improve the diagnose and treatment of SLE. Herein, a selenium nanosystem (DNA-SeNPs) with surface decoration of calf thymus DNA (ctDNA) was constructed to specifically recognize and remove anti-dsDNA autoantibodies in the serums of 128 SLE patients and in the kidneys of 36 LN patients. The nanotherapeutics exhibited perfect biocompatibility and safety in patients to directly eliminate anti-dsDNA antibodies. In addition, the clearance ratio of anti-dsDNA antibodies by DNA-SeNPs was notably higher than other products widely used in clinical practice, implying that the excellent removal efficiency of this nanotherapeutics. Importantly, DNA-SeNPs not only help to visualize the distribution of anti-dsDNA antibodies in the lesions of kidney, but also semi-quantify the deposition of these antibodies, which are the key cause of the local damage. To sum up, this study provides a simple approach for rational design of nanoscale SLE-targeting nanomedicine to improve the diagnose and treatment of SLE, also sheds light on the possible mechanisms of anti-dsDNA antibodies in the pathogenesis and progression of SLE.