eGFP标记的ZnO纳米颗粒通过靶向铁死亡和MRP1治疗头颈部鳞状细胞癌

文献信息

中文摘要

背景： 头颈部鳞状细胞癌（HNSCC）仍然是全球范围内最具侵袭性的恶性肿瘤之一，因此需要开发靶向治疗策略。虽然氧化锌（ZnO）纳米结构在纳米医学中显示出前景，但纳米颗粒形态对HNSCC的机制影响仍知之甚少。
方法： 在本研究中，我们使用总多酚（TP）作为还原剂和稳定剂，合成并表征了绿色合成的球形ZnO纳米颗粒（NPs）和刺状ZnO纳米颗粒（SNPs）。为了追踪细胞相互作用，这些纳米结构进一步用胶质母细胞瘤来源的eGFP标签进行了修饰。我们使用2D培养、3D多细胞球体和细胞内化实验，在多种HNSCC细胞系（Fadu、TU212和TU686）中评估了抗肿瘤功效及其潜在机制。
结果： 化学表征揭示了球形和刺状形态之间的明显结构变化。两种纳米颗粒均表现出显著的剂量依赖性抗癌活性；然而，ZnO SNPs在3D球体模型中表现出更优的内化和更明显的肿瘤抑制作用。值得注意的是，与喉癌细胞系（TU212和TU686）相比，ZnO SNPs在高度侵袭性的下咽癌细胞系（Fadu）中显示出更高的疗效。
结论： 机制研究表明，ZnO SNPs通过调节活性氧（ROS）产生、下调多药耐药相关蛋白1（MRP1）和抑制谷胱甘肽过氧化物酶4（GPX4）来发挥其抗肿瘤作用。这种协同作用触发了有效的ROS诱导的铁死亡。我们的研究结果表明，ZnO SNPs的分级形态增强了其治疗潜力，为治疗侵袭性HNSCC提供了一种新的靶向方法。

英文摘要

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) remain one of the most aggressive malignancies worldwide, necessitating the development of targeted therapeutic strategies. While zinc oxide (ZnO) nanostructures have shown promise in nanomedicine, the mechanistic influence of nanoparticle morphology on HNSCC remains poorly understood.
METHODS: In this study, we synthesized and characterized green-synthesized spherical ZnO nanoparticles (NPs) and spiky ZnO nanoparticles (SNPs) using total polyphenols (TP) as a reducing and stabilizing agent. To track cellular interactions, the nanostructures were further modified with glioblastoma-derived eGFP tags. The antitumor efficacy and underlying mechanisms were evaluated across multiple HNSCC cell lines (Fadu, TU212, and TU686) using 2D cultures, 3D multicellular spheroids, and cellular internalization assays.
RESULTS: Chemical characterization revealed distinct architectural shifts between the spherical and spiky morphologies. Both nanoparticle types demonstrated significant dose-dependent anticancer activity; however, ZnO SNPs exhibited superior internalization and more pronounced tumor suppression in 3D spheroid models. Notably, ZnO SNPs showed higher efficacy in the highly aggressive hypopharyngeal cancer line (Fadu) compared to laryngeal carcinoma lines (TU212 and TU686).
CONCLUSION: Mechanistic investigations revealed that ZnO SNPs exert their antitumor effects by modulating reactive oxygen species (ROS) production, downregulating multidrug resistance-associated protein 1 (MRP1), and inhibiting glutathione peroxidase 4 (GPX4). This synergy triggers potent ROS-induced ferroptosis. Our findings suggest that the hierarchical morphology of ZnO SNPs enhances their therapeutic potential, offering a novel, targeted approach for the treatment of aggressive HNSCC.