Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
The Second Affiliated Hospital of Xuzhou Medical University, 32 Meijian Road, Xuzhou, Jiangsu, 221006, China.
Curr Drug Deliv. 2023;20(9):1368-1379. doi: 10.2174/1567201819666220613145417.
Pulmonary fibrosis (PF) is a chronic and progressive interstitial lung disease. There is no effective treatment for PF. Hepatocyte growth factor (HGF) has anti-inflammatory and antifibrotic effects but has limited potential owing to its short half-life.
To increase the transfection efficiency of pVAX-HGF, we prepared polyethyleneiminepolyethylene glycol: polyethyleneimine/pVAX-HGF (PEG-PEI: PEI/pVAX-HGF) nanocomposite loaded with a plasmid encoding the HGF gene. The PEG-PEI:PEI/pVAX-HGF characteristics, including morphology, particle size, zeta-potential, and DNA entrapment efficiency, were investigated. The pVAX-HGF nanocomposites with low toxicity and high transfection efficiency were screened by cell viability assay and cell transfection. The antifibrotic effect of pVAX-HGF nanocomposite on PF rats induced by bleomycin (BLM) was evaluated by pulmonary function measurement, pathological examination and collagen content assay.
Different nanocomposites were prepared to deliver pVAX-HGF, in which mix1 (PEGPEI: PEI/pVAX-HGF) has lower potential and better entrapment ability.
PEG-PEI: PEI/pVAX-HGF (N/P=25) nanocomposite with low toxicity and high transfection efficiency was administered to PF rats. After treatment with mix 1/pVAX-HGF, the index of lung function(including EF50, MV, TV, PEF and PIF) in mix 1/pVAX-HGF group was higher than that of the PF group. The number of cells in BALF of the mix 1/pVAX-HGF group was significantly lower than that of the PF groups, and the content of hydroxyproline(HYP) and collagen Type I (Col-I) in the lung of the mix 1/pVAX-HGF group was much lower than that of the PF groups in the early stage. The result of pathological examination showed that rats in the mix1/pVAX-HGF group showed obviously reduced alveolar septal thickening, fewer infiltrated inflammatory cells and less collagen deposition.
The PEG-PEI:PEI/pVAX-HGF nanocomposite can ameliorate PF induced by BLM. The pVAX-HGF nanocomposite is a latent therapeutic strategy for PF.
肺纤维化（PF）是一种慢性进行性间质性肺疾病。目前尚无有效的 PF 治疗方法。肝细胞生长因子（HGF）具有抗炎和抗纤维化作用，但由于半衰期短，其应用潜力有限。
为了提高 pVAX-HGF 的转染效率，我们制备了聚乙烯亚胺-聚乙二醇：聚乙烯亚胺/pVAX-HGF（PEG-PEI：PEI/pVAX-HGF）纳米复合物，其中负载了一个编码 HGF 基因的质粒。研究了 PEG-PEI：PEI/pVAX-HGF 的特征，包括形态、粒径、Zeta 电位和 DNA 包封效率。通过细胞活力测定和细胞转染筛选出毒性低、转染效率高的 pVAX-HGF 纳米复合物。通过肺功能测定、病理检查和胶原含量测定评估 pVAX-HGF 纳米复合物对博来霉素（BLM）诱导的 PF 大鼠的抗纤维化作用。
制备了不同的纳米复合物来递送 pVAX-HGF，其中 mix1（PEG-PEI：PEI/pVAX-HGF）具有较低的电位和更好的包封能力。毒性低、转染效率高的 PEG-PEI：PEI/pVAX-HGF（N/P=25）纳米复合物用于 PF 大鼠。与 mix1/pVAX-HGF 治疗后，mix1/pVAX-HGF 组的肺功能指标（包括 EF50、MV、TV、PEF 和 PIF）均高于 PF 组。mix1/pVAX-HGF 组 BALF 中的细胞数明显低于 PF 组，早期 mix1/pVAX-HGF 组肺中的羟脯氨酸（HYP）和胶原 I 型（Col-I）含量明显低于 PF 组。病理检查结果表明，mix1/pVAX-HGF 组大鼠肺泡间隔增厚明显减轻，浸润的炎性细胞减少，胶原沉积减少。
PEG-PEI：PEI/pVAX-HGF 纳米复合物可改善 BLM 诱导的 PF。pVAX-HGF 纳米复合物是 PF 的一种潜在治疗策略。
