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

Abstract

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.