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Ampicillin-Loaded Fenugreek-Derived Exosomes Treat COPD via Anti-Inflammatory, Antibacterial and Anti-Fibrotic
Haidiya Aierken1, Bing Jia1, Bahaerguli Aikeranmu2
1Respiratory Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People's Republic of China.
Purpose:
Chronic Obstructive Pulmonary Disease (COPD) is a major global health issue characterized by progressive airflow limitation, chronic inflammation, and recurrent infections. Current treatments largely alleviate symptoms but fail to simultaneously address infection-driven and inflammation-driven disease progression. Exosome-based strategies offer a promising alternative, and plant-derived exosomes possess distinct advantages, including low immunogenicity, natural abundance, and simple isolation compared with mammalian exosomes.
Methods:
We developed a novel dual-functional nanotherapeutic agent by loading ampicillin into exosomes derived from Trigonella foenum-graecum. The resulting ampicillin-loaded exosomes (Exos-AM) harness the natural bioactivity and biocompatibility of plant exosomes to improve drug stability and cellular delivery. The therapeutic efficacy of Exos-AM was evaluated in a murine COPD model induced by lipopolysaccharide (LPS) instillation, cigarette smoke exposure, and P. aeruginosa infection.
Results:
In vitro, Exos-AM exhibited potent antibacterial activity against S. aureus, E. coli, and P. aeruginosa, while promoting macrophage polarization toward the anti-inflammatory M2 phenotype, thereby alleviating inflammation and attenuating fibrotic responses. Transcriptomic analysis further revealed that Exos-AM modulated macrophage activation through suppression of the NF-κB and MAPK signaling pathways, providing mechanistic insight into its anti-inflammatory effects. In vivo, Exos-AM treatment significantly improved lung histopathology and enhanced bacterial clearance.
Conclusion:
Our findings underscore the promise of plant-derived exosomes as versatile drug delivery platforms and position Exos-AM as a compelling therapeutic strategy for COPD by concurrently targeting infectious and inflammatory drivers.
Insights
This study introduces ampicillin-loaded plant exosomes (Exos-AM) as a novel treatment for Chronic Obstructive Pulmonary Disease (COPD). Exos-AM effectively targets both infection and inflammation, improving lung health in a COPD mouse model.
Area of Science:
- Biotechnology and Nanomedicine
- Respiratory Medicine
- Immunology
Background:
- Chronic Obstructive Pulmonary Disease (COPD) is a progressive respiratory disease with significant global health impact.
- Current COPD treatments offer symptomatic relief but do not fully address the underlying infection and inflammation.
- Plant-derived exosomes present advantages over mammalian exosomes for therapeutic applications due to low immunogenicity and ease of isolation.
Purpose of the Study:
- To develop and evaluate a novel dual-functional nanotherapeutic agent for COPD treatment.
- To investigate the efficacy of ampicillin-loaded exosomes derived from Trigonella foenum-graecum (Exos-AM) in a murine COPD model.
Main Methods:
- Developed ampicillin-loaded exosomes (Exos-AM) using plant-derived exosomes for enhanced drug delivery.
- Induced a COPD model in mice using lipopolysaccharide, cigarette smoke, and Pseudomonas aeruginosa infection.
- Assessed Exos-AM's antibacterial activity, anti-inflammatory effects on macrophages, and therapeutic efficacy in vivo.
Main Results:
- Exos-AM demonstrated potent in vitro antibacterial activity and promoted anti-inflammatory M2 macrophage polarization.
- Transcriptomic analysis revealed Exos-AM suppresses NF-κB and MAPK signaling pathways, reducing inflammation and fibrosis.
- In vivo, Exos-AM treatment improved lung histopathology and bacterial clearance in the COPD model.
Conclusions:
- Plant-derived exosomes are effective drug delivery platforms for COPD.
- Exos-AM shows promise as a therapeutic strategy for COPD, simultaneously addressing infectious and inflammatory components.
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