Shi Yanan, Zhang Houqian, Chen Hao, Guo Jianwei, Yuan Ranran, Tian Yu, Xin Quanlin, Mu Zhen, Tao Yuping, Chu Yongchao, Wang Aiping, Zhang Zhiwen, Tian Jingwei, Wang Hongbo
Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, School of Pharmacy, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China.
Shandong Laboratory of Advanced Materials and Green Manufacturing at Yantai, Yantai 264006, China.
Int J Mol Sci. 2025 Jan 30;26(3):1196. doi: 10.3390/ijms26031196.
Transforming growth factor-β (TGF-β) promotes the growth and metastasis of lung cancer cells. Therefore, TGF-β siRNA (siTGF-β) gene therapy was introduced to inhibit the expression of TGF-β at the nucleic acid level to avert tumor growth and metastasis. However, the delivery of naked siRNA is typically restricted by a short half-life in vivo, difficulties in delivery in vivo, and safety issues. Using siTGF-β as a model drug, we established an actively targeted immunoliposome delivery system to investigate the role of siTGF-β in non-small-cell lung cancer (NSCLC). The results showed that the constructed immune liposomes were in a position to deliver siTGF-β to tumor cells, thus achieving a series of effects such as improving the poor stability and short half-life of naked siRNA. RNA interference of siTGF-β reduced the cell viability, growth, and migration potential of human non-small cell lung cancer cells (A549). Moreover, in an A549 tumor-bearing nude mouse model, siTGF-β transfection markedly reduced tumor growth and tumor volume. Inhibiting TGF-β diminished cancer cell viability and migration and promoted apoptosis in NSCLC, as confirmed by the findings of this study. Therefore, targeting siTGF-β with immunoliposomes may be a new therapeutic strategy for treating non-small-cell lung cancer.
转化生长因子-β（TGF-β）促进肺癌细胞的生长和转移。因此，引入TGF-β小干扰RNA（siTGF-β）基因疗法以在核酸水平抑制TGF-β的表达，从而避免肿瘤生长和转移。然而，裸siRNA的递送通常受到体内半衰期短、体内递送困难以及安全性问题的限制。以siTGF-β作为模型药物，我们建立了一种主动靶向免疫脂质体递送系统，以研究siTGF-β在非小细胞肺癌（NSCLC）中的作用。结果表明，构建的免疫脂质体能够将siTGF-β递送至肿瘤细胞，从而实现一系列效果，如改善裸siRNA稳定性差和半衰期短的问题。siTGF-β的RNA干扰降低了人非小细胞肺癌细胞（A549）的细胞活力、生长和迁移潜能。此外，在A549荷瘤裸鼠模型中，siTGF-β转染显著降低了肿瘤生长和肿瘤体积。本研究结果证实，抑制TGF-β可降低NSCLC中的癌细胞活力和迁移，并促进细胞凋亡。因此，用免疫脂质体靶向siTGF-β可能是治疗非小细胞肺癌的一种新的治疗策略。
