Gold nanoparticles mediate suppression of angiogenesis and breast cancer growth via MMP-9/NF-κB/mTOR and PD-L1/PD-1 signaling: integrative in vitro validation and network pharmacology insights

被引：1

作者：

Alaa Elmetwalli ^{[1
]}

Tarek El-Sewedy ^{[2
]}

Mervat G. Hassan ^{[3
]}

Mohamed O. Abdel-Monem ^{[4
]}

Jihan Hassan ^{[4
]}

Nadia F. Ismail ^{[3
]}

Afrah Fatthi Salama ^{[5
]}

Junjiang Fu ^{[6
]}

Nasser Mousa ^{[7
]}

Deema Kamal Sabir ^{[8
]}

Ola El-Emam ^{[9
]}

Ghada Hamdy ^{[10
]}

Ali H. El-Far ^{[2
]}

机构：

[1] Department of Clinical Trial Research Unit and Drug Discovery, Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura

[2] Higher Technological Institute of Applied Health Sciences, Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura

[3] Department of Applied Medical Chemistry, Medical Research Institute, Alexandria University, Alexandria

[4] Department of Botany and Microbiology, Faculty of Science, Benha University, Benha

[5] Health Information Management Program, Biochemistry, Faculty of Health Science Technology, Borg El Arab Technological University, Alexandria

[6] Biochemistry Section, Chemistry Department, Faculty of Science, Tanta University, Tanta

[7] Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou

[8] Tropical Medicine Department, Faculty of Medicine, Mansoura University, Mansoura

[9] Department of Medical Surgical Nursing, College of Nursing, Princess Nourah bint Abdulrahman University, P.O.Box 84428, Riyadh

[10] Clinical Pathology Department, Mansoura University, Mansoura

[11] Department of Biochemistry, Faculty of Veterinary Medicine, Damanhour University, Damanhour

来源：

Naunyn-Schmiedeberg's Archives of Pharmacology | 2025年 / 398卷 / 6期

关键词：

Breast cancer; Cancer therapy; Cytotoxicity; Gene expression analysis; Gold nanoparticles;

D O I：

10.1007/s00210-024-03682-8

中图分类号：

学科分类号：

摘要：

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. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.

引用

页码：7087 / 7105

页数：18

共 70 条

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