Advanced nanoformulations of NUAK1 regulate NLRP3 inflammasome for preeclampsia management in mice.

Preeclampsia (PE) is a severe pregnancy complication driven by placental dysfunction and oxidative stress, which currently lacks effective targeted therapies. Here, we evaluated the therapeutic potential of folic acid-modified lipid nanoparticles (NPs) co-loaded with polydopamine and NUAK Family Kinase 1 (NUAK1), termed FLN@(PDA + NUAK1) NPs, for mitigating PE. In vitro, these NPs effectively reduced reactive oxygen species levels and suppressed activation of the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome, while promoting autophagic activity and inhibiting apoptosis under oxidative stress. In vivo analysis using an L-NAME-induced PE mouse model further confirmed that FLN@(PDA + NUAK1) NPs improved placental structure and fetal growth parameters. This study highlights the dual functionality of NPs in activating protective autophagy and suppressing inflammasome overactivation, offering a promising strategy for the treatment of PE.