Elmetwalli Alaa, El-Sewedy Tarek, Hassan Mervat G, Abdel-Monem Mohamed O, Hassan Jihan, Ismail Nadia F, Salama Afrah Fatthi, Fu Junjiang, Mousa Nasser, Sabir Deema Kamal, El-Emam Ola, Hamdy Ghada, El-Far Ali H
Department of Clinical Trial Research Unit and Drug Discovery, Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt.
Higher Technological Institute of Applied Health Sciences, Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Dec 24. doi: 10.1007/s00210-024-03682-8.
Gold nanoparticles (AuNPs) have emerged as promising candidates for cancer therapy due to their unique physicochemical properties and biocompatibility. In this study, we investigate the synthesis, characterization, and therapeutic potential of AuNPs in breast cancer treatment. Further, it establishes a comprehensive understanding of the mechanisms by which AuNPs suppress angiogenesis and breast cancer growth, identifying novel targets and signaling nodes contributing to the anti-tumor effects of AuNPs. AuNPs were synthesized and characterized using UV-Vis, crystallography, transmission electron microscopy (TEM), and energy-dispersive X-ray spectroscopy (EDX). The cytotoxicity of AuNPs was evaluated in WI-38 normal cells and MCF-7 breast cancer cells using the MTT assay. Additionally, the antioxidant activity of AuNPs was assessed through free radical scavenging and lipid peroxidation inhibition assays. Gene expression and pathway enrichment analyses were performed to elucidate the molecular mechanisms underlying the therapeutic effects of AuNPs in breast cancer. UV-Vis spectroscopy confirmed the successful synthesis of AuNPs, with a strong peak observed at 488.9 nm. Crystallography and TEM analysis revealed the crystalline nature and uniform size distribution of AuNPs, respectively. AuNPs exhibited concentration-dependent cytotoxic effects on MCF-7 cells, significantly inhibiting cancer cell proliferation at lower concentrations. Moreover, AuNPs demonstrated potent antioxidant activity, surpassing the effectiveness of vitamin C in scavenging free radicals and inhibiting lipid peroxidation. Gene expression analysis revealed modulation of crucial cancer-related genes and signaling pathways, including MMP-9/NF-κB/mTOR, PD-L1 expression and PD-1 checkpoint pathway, TNF signaling pathway, and adipocytokine signaling pathway, suggesting their potential as novel therapeutics for breast cancer treatment. Our findings support the promising role of AuNPs as effective and targeted therapeutics for breast cancer treatment. Further research is warranted to elucidate the precise mechanisms of action and evaluate the clinical efficacy and safety of AuNP-based therapies in breast cancer patients.
由于其独特的物理化学性质和生物相容性，金纳米颗粒（AuNPs）已成为癌症治疗中很有前景的候选材料。在本研究中，我们研究了AuNPs在乳腺癌治疗中的合成、表征及治疗潜力。此外，本研究还全面了解了AuNPs抑制血管生成和乳腺癌生长的机制，确定了有助于AuNPs抗肿瘤作用的新靶点和信号节点。利用紫外可见光谱、晶体学、透射电子显微镜（TEM）和能量色散X射线光谱（EDX）对AuNPs进行了合成和表征。使用MTT法在WI-38正常细胞和MCF-7乳腺癌细胞中评估AuNPs的细胞毒性。此外，通过自由基清除和脂质过氧化抑制试验评估AuNPs的抗氧化活性。进行基因表达和通路富集分析，以阐明AuNPs在乳腺癌治疗中发挥治疗作用的分子机制。紫外可见光谱证实成功合成了AuNPs，在488.9nm处观察到一个强峰。晶体学和TEM分析分别揭示了AuNPs的晶体性质和均匀的尺寸分布。AuNPs对MCF-7细胞表现出浓度依赖性的细胞毒性，在较低浓度下能显著抑制癌细胞增殖。此外，AuNPs表现出强大的抗氧化活性，在清除自由基和抑制脂质过氧化方面超过了维生素C的效果。基因表达分析揭示了关键的癌症相关基因和信号通路的调节，包括MMP-9/NF-κB/mTOR、PD-L1表达和PD-1检查点通路、TNF信号通路和脂肪细胞因子信号通路，表明它们作为乳腺癌治疗新疗法的潜力。我们的研究结果支持AuNPs作为乳腺癌治疗的有效和靶向疗法的前景。有必要进一步研究以阐明其确切作用机制，并评估基于AuNP的疗法在乳腺癌患者中的临床疗效和安全性。
