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Outline
Pulmonary fibrosis (PF) is a progressive and irreversible interstitial lung disease of unknown etiology with limited therapeutic options. Bioinformatics enrichment analysis indicates that oxidative stress and metabolic dysregulation of alveolar epithelial type II cells (AECs II) may contribute to PF pathogenesis. With recent advances in molecular biology and genetic engineering, gene therapy has emerged as a promising therapeutic strategy for PF. However, its clinical translation remains challenging due to biological barriers that hinders efficient delivery of therapeutic genes. To address this limitation, we explored main factors affecting transfection efficiency and screened optimal prescription to develop nanocomplexes (NPs@pSIRT3) via delivery of sirtuin 3 plasmid (pSIRT3) to treat PF. The NPs@pSIRT3 exhibited superior transfection efficiency, mediating robust SIRT3 protein expression to achieve therapeutic efficacy. Comparative analysis with excipient-deficient control groups demonstrated that the optimized nanoparticles (NPs) effectively delivered therapeutic genes to fibrotic lesions, enhancing pSIRT3 transfection. The NPs@pSIRT3 significantly attenuated PF progression by modulating oxidative stress normalization of injured AECs II, anti-inflammatory effects, and finally inhibition of pro-fibrotic responses. These findings demonstrate that the engineered NPs@pSIRT3 system represents a promising gene delivery platform for PF therapy, and providing a novel strategy for efficient transfection of gene therapy. All animal procedures were performed in accordance with the guidelines of and approved by the Institutional Animal Care and Use Committee of Jinzhou Medical University (approval number: 240134-5).
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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