MicroRNA-125a-Loaded Polymeric Nanoparticles Alleviate Systemic Lupus Erythematosus by Restoring Effector/Regulatory T Cells Balance.
Jiali ZhangChuanrong ChenHao FuJian YuYing SunHui HuangYuanjia TangNan ShenYourong DuanPublished in: ACS nano (2020)
Systemic lupus erythematosus (SLE), a common lethal autoimmune disease, is characterized by effector/regulatory T cells imbalance. Current therapies are either inefficient or have severe side effects. MicroRNA-125a (miR-125a) can stabilize Treg-mediated self-tolerance by targeting effector programs, but it is significantly downregulated in peripheral T cells of patients with SLE. Therefore, overexpression of miR-125a may have therapeutic potential to treat SLE. Considering the stability and targeted delivery of miRNA remains a major challenge in vivo, we constructed a monomethoxy (polyethylene glycol)-poly(d,l-lactide-co-glycolide)-poly(l-lysine) (mPEG-PLGA-PLL) nanodelivery system to deliver miR-125a into splenic T cells. Results demonstrate that miR-125a-loaded mPEG-PLGA-PLL (PEALmiR-125a) nanoparticles (NPs) exhibit good biocompatibility and protect miR-125a from degradation, thereby prolonging the circulatory time of miRNA in vivo. In addition, PEALmiR-125a NPs are preferentially enriched in a pathological spleen and efficiently deliver miR-125a into the splenic T cells in SLE mice models. The PEALmiR-125a NPs treatment significantly alleviates SLE disease progression by reversing the imbalance of effector/regulatory T cells. Collectively, the PEALmiR-125a NPs show excellent therapeutic efficacy and safety, which may provide an effective treatment for SLE.
Keyphrases
- regulatory t cells
- systemic lupus erythematosus
- cell proliferation
- long non coding rna
- disease activity
- dendritic cells
- long noncoding rna
- drug delivery
- rheumatoid arthritis
- metabolic syndrome
- cancer therapy
- transcription factor
- adipose tissue
- skeletal muscle
- extracorporeal membrane oxygenation
- mouse model
- smoking cessation