Liu Ting, Lin Zhiming, Zhang Xi, Yang Yu, Huang Guanning, Yu Yanzi, Xie Bin, He Lizhen, Chen Tianfeng
The Department of Chemistry Department of Neurology and Stroke Center of The First Affliated Hospital State Key Laboratory of Bioactive Molecules and Druggablily Assessment MOE Key Laboratory of Viral Pathogenesis and lnfection Prevention and Control Jinan University Guangzhou 510632 China.
Division of Rheumatology Third Affiliated Hospital of Sun Yat-Sen University Guangzhou 510630 China.
Small Sci. 2025 Jan 23;5(5):2400521. doi: 10.1002/smsc.202400521. eCollection 2025 May.
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.
系统性红斑狼疮（SLE）的特征是产生致病性自身抗体，尤其是抗双链（ds）DNA抗体，这些抗体导致多器官损伤（狼疮性肾炎，LN）。因此，迫切需要识别和清除SLE特异性抗dsDNA抗体以加强SLE治疗。在此，构建了负载硒化镉（SeC）并经表面修饰的小牛胸腺DNA（ctDNA）的介孔二氧化硅（MSNs），以有效特异性结合并清除致病性抗dsDNA抗体，用于治疗125例血浆中的SLE，并能快速诊断36例SLE患者肾脏组织中的LN。正如预期的那样，与临床治疗中常用的其他产品相比，纳米疗法对抗dsDNA抗体的清除率显著更高，并且在患者中表现出生物相容性和安全性。此外，MSNs-DNA还可以帮助可视化抗dsDNA抗体在肾脏病变中的分布。重要的是，联合策略（MSNs-DNA@SeC）可以通过调节雌性MRL/lpr SLE模型小鼠中的B细胞和T细胞来有效清除抗体并减少尿蛋白（UP）产生，从而减轻相关症状。总的来说，所得数据不仅为系统性设计靶向SLE的纳米药物以增强诊断和治疗效果提供了一种直接的方法，而且还阐明了抗dsDNA抗体在SLE发病机制和进展中的潜在作用机制。
