Biomimetic Nanoparticles Loaded With α‐Cyperone Alleviating LPS‐Induced Inflammation in KGN Cells by Activating Nrf2/HO‐1 and Suppressing ROS

Diminished ovarian reserve (DOR) is a leading cause of female infertility, and currently, no effective therapeutic options are available. α‐Cyperone (AC) possesses various pharmacological properties, including anti‐inflammatory and antioxidant effects. However, its clinical application is hindered by poor water solubility, a short half‐life, and nonspecific toxicity. In this study, we utilized nanotechnology to develop a novel dual‐targeted nanocomplex, termed PLGA@AC@FSHL‐M (PAMF) nanoparticles (NPs), comprising poly(lactic‐co‐glycolic acid) (PLGA) encapsulating AC and camouflaged with a macrophage membrane modified by the FSHL81‐95 peptide. This design enabled efficient delivery of AC while simultaneously targeting granulosa cells (GCs). Our findings demonstrated that PAMF NPs significantly reduced the production of tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), and interleukin‐1β (IL‐1β) in lipopolysaccharide (LPS)‐induced KGN cells. Furthermore, AC‐loaded PAMF NPs enhanced nuclear translocation of nuclear factor erythroid 2–related factor 2 (Nrf2) and upregulated heme oxygenase‐1 (HO‐1), while inhibiting NF‐κβ activation. These results suggest that biomimetic AC‐loaded nanoparticles effectively suppress apoptosis and promote proliferation under inflammatory conditions in KGN cells, offering a promising therapeutic strategy for DOR.