The Protective Effect And Underlying Mechanisms Of Phosphatidylserine Modified Gold Nanocages Loaded With LXR Agonist For The Treatment Of Systemic Lupus Erythematosus

[Background and purpose]Investigation of the therapeutic effect and safety profile of phosphatidylserine modified gold nanocages loaded with LXR agonist T0901317 for targeted delivery to macrophages for the treatment of SLE.[Methods]Flow cytometry analysis and fluorescent imaging were performed to evaluate of the capability of apoptotic cell phagocytosis by BMDM;determination of 24 h urine protein with Coomassie brilliant blue staining;ELISA for the analysis of serum creatinine and dsDNA antibody levels was performed;CBA mix beads for the analysis of the serum levels of pro-inflammatory cytokines;fluorescent imaging of the IgG deposit in the kidney;flow cytometry analysis was also used to investigate the expression level of Mer on the surface of CD169+ macrophages;histopathologic examination of the liver to investigate liver damage.[Results]BMDMs from T0901317@Lipo-AuNC-PS treated lupus mice exhibited enhanced phagotytotic capability of apoptotic cells compared with those treated with T0901317@Lipo-AuNC,T0901317,Lipo-AuNC-PS,Lipo-AuNC and PBS.T0901317@Lipo-AuNC-PS could significantly decrease the levels of 24 h urine protein and serum creatinine,inhibit IgG deposit in the kidney and lower the serum levels of anti-dsDNA antibody and pro-inflammatory cytokines such as IL-6,TNF-a and IFN-y.Additionally,T0901317@Lipo-AuNC-PS could increase the expression level of Mer on the surface of CDi69+ macrophages and improve the phagocytotic capability of apoptotic cells.Finally,T0901317@Lipo-AuNC-PS could prolong its retention in the targeted organs and reduce the side effect of liver damage caused by T0901317.[Conclusions]T0901317@Lipo-AuNC-PS could alleviate kidney damage and decrease the serum levels of anti-dsDNA antibody and pro-inflammatory cytokines.Additionally,T0901317@Lipo-AuNC-PS could also improve the phagocytotic capability of CD 169+macrophages by elevating the expression level of Mer on their surfaces.Furthermore,.T0901317@Lipo-AuNC-PS could prolong its retention in the targeted organs and reduce the adverse effect of liver damage caused by T0901317.In conclusion,our study provides a promising strategy in the treatment of SLE with the aid of targeted nanoparticle drug delivery system.