Cetuximab-Immunoliposomes Loaded with TGF-β1 siRNA for the Targeting Therapy of NSCLC: Design, and In Vitro and In Vivo Evaluation

用于靶向治疗非小细胞肺癌的西妥昔单抗-TGF-β1 siRNA免疫脂质体:设计、体外和体内评价

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Abstract

Transforming growth factor-β(1) (TGF-β(1)) promotes the growth and metastasis of lung cancer cells. Therefore, TGF-β(1) siRNA (siTGF-β(1)) gene therapy was introduced to inhibit the expression of TGF-β(1) 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(1) as a model drug, we established an actively targeted immunoliposome delivery system to investigate the role of siTGF-β(1) in non-small-cell lung cancer (NSCLC). The results showed that the constructed immune liposomes were in a position to deliver siTGF-β(1) 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(1) 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(1) transfection markedly reduced tumor growth and tumor volume. Inhibiting TGF-β(1) diminished cancer cell viability and migration and promoted apoptosis in NSCLC, as confirmed by the findings of this study. Therefore, targeting siTGF-β(1) with immunoliposomes may be a new therapeutic strategy for treating non-small-cell lung cancer.

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