Laboratory Animal Center Shanxi Key Laboratory of Experimental Animal Science and Human Disease Animal Model, Shanxi Medical University, Taiyuan, People's Republic of China.
School of Basic Medical Science, Shanxi Medical University, Taiyuan, People's Republic of China.
Int J Nanomedicine. 2024 Sep 7;19:9227-9253. doi: 10.2147/IJN.S458484. eCollection 2024.
Oral squamous cell carcinoma is the most common type of malignant tumor in the head and neck region. Despite advancements, metastasis and recurrence rates remain high, and patient survival has not significantly improved. Although miRNA therapies are promising for cancer gene therapy, their applications in treating oral cancer are limited. Targeted medication delivery systems based on nanotechnology offer an efficient way to enhance oral cancer treatment efficacy.
We synthesized nanosilver (AgNPs) and loaded them with the tumor suppressor miR-181a-5p. In vitro experiments were conducted to investigate the inhibitory effects of AgNPs and their composites on the malignant behavior of oral cancer cell lines. The xenograft experiment was utilized to examine their effects on tumorigenesis and the potential molecular mechanisms involved.
The nanosilver exhibited a spherical morphology with a size distribution ranging from 50 to 100 nm. They exhibited a distinct absorption peak at 330 nm and could be excited to emit green fluorescence. The biocompatible AgNPs effectively shielded miRNA from degradation by RNase and serum. The nanocomposites significantly inhibited the proliferation, invasion, migration, and colony formation of oral cancer cell lines. Notably, treatment with the nanocomposites resulted in substantial tumor growth suppression in the xenograft model. Mechanistically, these composites directly targeted BCL2 and exerted their antitumor effects by suppressing the β-catenin signaling pathway and other downstream genes without inducing acute toxicity.
Collectively, the findings demonstrate that the miR-181a-5p/AgNPs combination significantly impedes the growth and progression of oral cancer both in vitro and in vivo, highlighting a pivotal role for the β-catenin signaling pathway. This multifaceted approach holds promise as a prospective therapeutic strategy for oral cancer management in the future.
口腔鳞状细胞癌是头颈部最常见的恶性肿瘤。尽管取得了进展，但转移和复发率仍然很高，患者的生存率并没有显著提高。虽然 miRNA 疗法在癌症基因治疗中很有前景，但它们在治疗口腔癌方面的应用有限。基于纳米技术的靶向药物输送系统为提高口腔癌治疗效果提供了一种有效的方法。
我们合成了纳米银（AgNPs）并将其负载肿瘤抑制因子 miR-181a-5p。进行了体外实验以研究 AgNPs 及其复合材料对口腔癌细胞系恶性行为的抑制作用。利用异种移植实验研究它们对肿瘤发生的影响及其潜在的分子机制。
纳米银呈球形形态，粒径分布在 50 至 100nm 之间。它们在 330nm 处表现出明显的吸收峰，并能被激发发出绿色荧光。生物相容性的 AgNPs 能有效地保护 miRNA 免受 RNase 和血清的降解。纳米复合材料能显著抑制口腔癌细胞系的增殖、侵袭、迁移和集落形成。值得注意的是，纳米复合材料治疗在异种移植模型中导致肿瘤生长显著抑制。从机制上讲，这些复合材料通过抑制 β-连环蛋白信号通路和其他下游基因来发挥其抗肿瘤作用，而不会引起急性毒性，直接靶向 BCL2。
综上所述，研究结果表明，miR-181a-5p/AgNPs 联合显著抑制口腔癌在体外和体内的生长和进展，强调了β-连环蛋白信号通路的关键作用。这种多方面的方法有望成为未来口腔癌管理的一种有前途的治疗策略。
