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Biomimetic Nanoparticles Loaded With α-Cyperone Alleviating LPS-Induced Inflammation in KGN Cells by Activating
Jialing Li1, Fengzhi Li2, Xue Chen3
1Reproductive Medicine Center, General Hosptial of Ningxia Medical University, Yinchuan, China.
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.
Insights
Novel nanoparticles deliver α-cyperone (AC) to ovarian cells, reducing inflammation and apoptosis. This nanotechnology offers a promising new treatment for diminished ovarian reserve (DOR) and female infertility.
Area of Science:
- Reproductive Biology
- Nanomedicine
- Pharmacology
Background:
- Diminished ovarian reserve (DOR) is a primary cause of female infertility with limited therapeutic options.
- α-Cyperone (AC) has anti-inflammatory and antioxidant properties but faces challenges in clinical use due to poor solubility and toxicity.
- Nanotechnology offers a potential solution for targeted drug delivery and improved therapeutic efficacy.
Purpose of the Study:
- To develop a dual-targeted nanocomplex (PAMF NPs) for efficient delivery of α-cyperone (AC) to granulosa cells (GCs).
- To evaluate the therapeutic potential of PAMF NPs in an in vitro model of inflammation relevant to DOR.
Main Methods:
- Development of PLGA@AC@FSHL-M (PAMF) nanoparticles encapsulating AC and camouflaged with macrophage membrane modified by FSHL81-95 peptide.
- Assessment of PAMF NPs' effects on inflammatory markers (TNF-α, IL-6, IL-1β) in LPS-induced KGN cells.
- Evaluation of Nrf2 nuclear translocation, HO-1 upregulation, and NF-κβ inhibition by AC-loaded PAMF NPs.
Main Results:
- PAMF NPs significantly reduced pro-inflammatory cytokine production (TNF-α, IL-6, IL-1β) in KGN cells.
- AC-loaded PAMF NPs promoted Nrf2 nuclear translocation and upregulated HO-1, indicating activation of antioxidant pathways.
- These nanoparticles effectively inhibited NF-κβ activation, a key inflammatory pathway.
- PAMF NPs suppressed apoptosis and promoted proliferation in KGN cells under inflammatory conditions.
Conclusions:
- Biomimetic AC-loaded nanoparticles (PAMF NPs) demonstrate effective targeted delivery and therapeutic action.
- PAMF NPs show significant anti-inflammatory and anti-apoptotic effects in an in vitro model of DOR.
- This nanotechnology-based approach presents a promising therapeutic strategy for treating diminished ovarian reserve.
