Department of Thoracic Surgery, Leshan People's Hospital, Leshan, 614000, China.
Appl Biochem Biotechnol. 2023 Jul;195(7):4067-4083. doi: 10.1007/s12010-022-04289-6. Epub 2023 Jan 18.
Metformin (Metf), a biguanide widely used to manage type 2 diabetes mellitus, has recently entered the spotlight as a hopeful anti-tumor agent. In this work, because of the hyaluronic acid (HA) capability to specifically target CD44 receptors over-expressed on the surface of non-small lung cancer cells, a tumor-targeted drug delivery nanocarrier-based HA-coated mesoporous silica nanoparticles (MSNs) have been used for active targeting and efficient delivery of Metf. For this purpose, the synthesized MSNs-HA were characterized using BET, FE-EM, DLS, and FTIR. Confocal microscopy was applied to show the enhanced cellular uptake of the FITC-labelled MSNs-HA compared to MSNs without HA coating. MTT and qPCR results also revealed superior cytotoxicity and pro-apoptotic effects of Metf-loaded MSNs-HA (Metf@MSNs-HA) against the A549 lung cancer cells compared to the free Metf and MSNs@Metf due to the efficient CD44-targeting capability and delivery of Metf@MSNs-HA. Besides, it was demonstrated that Metf@MSNs-HA could effectively trigger the AMP-activated protein kinase α (AMPKα) pathway and inhibit the mammalian target rapamycin (mTOR), increasing the growth suppression. In conclusion, this preliminary work disclosed the great potential of Metf@MSNs-HA in targeted therapy of lung cancer cells.
二甲双胍（Metf）是一种广泛用于治疗 2 型糖尿病的双胍类药物，最近作为一种有希望的抗肿瘤药物引起了人们的关注。在这项工作中，由于透明质酸（HA）能够特异性地靶向非小细胞肺癌细胞表面过表达的 CD44 受体，因此使用基于具有透明质酸（HA）涂层的介孔硅纳米粒子（MSNs）的肿瘤靶向药物递送纳米载体来主动靶向和有效递送电镜下观察到与未经 HA 涂层的 MSNs 相比，FITC 标记的 MSNs-HA 的细胞摄取增强。MTT 和 qPCR 结果还表明，与游离 Metf 和 MSNs@Metf 相比，载有 Metf 的 MSNs-HA（Metf@MSNs-HA）对 A549 肺癌细胞具有更高的细胞毒性和促凋亡作用，这是由于 Metf@MSNs-HA 的高效 CD44 靶向能力和递送。此外，研究表明，Metf@MSNs-HA 能够有效触发 AMP 激活的蛋白激酶 α（AMPKα）途径并抑制哺乳动物靶标雷帕霉素（mTOR），从而增加生长抑制。总之，这项初步工作揭示了 Metf@MSNs-HA 在肺癌细胞靶向治疗中的巨大潜力。
