Green-synthesized silver nanoparticles from peel extract of pumpkin as a potent radiosensitizer against triple-negative breast cancer (TNBC)

IF 4.5 2区 工程技术 Q2 NANOSCIENCE & NANOTECHNOLOGY Cancer Nanotechnology Pub Date : 2024-08-21 DOI:10.1186/s12645-024-00285-z
Soheila Montazersaheb, Aziz Eftekhari, Amir Shafaroodi, Soodeh Tavakoli, Sara Jafari, Ayşe Baran, Mehmet Fırat Baran, Sevda Jafari, Elham Ahmadian
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Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Radiation therapy (RT) is a modality for TNBC management. Radiosensitizers can mitigate the adverse effects of RT. Applying green-synthesized silver nanoparticles (Ag-NPs) from biological sources such as plants is a potential strategy to sensitize cancer cells to radiotherapy due to the low toxicity. Therefore, identifying novel natural sources for synthesizing stable and broadly applicable green-Ag-NPs has gained more attention in cancer therapy. In the present study, we synthesized green- Ag-NPs from pumpkin peel extract and elucidated the impact of green-synthesized Ag-NPs as a radiosensitizer in MDA-MB 231 cells (a model of TNBC). The prepared Ag-NPs had a spherical shape with an average size of 81 nm and a zeta potential of − 9.96 mV. Combination of green-synthesized Ag-NPs with RT exhibited synergistic anticancer effects with an optimum combination index (CI) of 0.49 in MDA-MB-231 cells. Green-synthesized Ag-NPs synergistically potentiated RT-induced apoptosis in MDA-MB-231 cells compared to the corresponding monotherapies. Morphological features of apoptosis were further confirmed by the DAPI–TUNEL staining assay. HIF-1α expression was decreased in cells subjected to combination therapy. Bax and p53 expression increased, whereas Bcl-2 genes decreased. Combination therapy significantly increased the protein level of PERK and CHOP while decreasing cyclin D1 and p-ERK/total ERK levels compared to monotherapies. These findings indicate the potential effect of green-synthesized Ag-NPs as a radiosensitizer for TNBC treatment.
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从南瓜皮提取物中提取的绿色合成银纳米粒子可作为抗三阴性乳腺癌(TNBC)的强效放射增敏剂
三阴性乳腺癌(TNBC)是乳腺癌的一种侵袭性亚型。放射治疗(RT)是治疗 TNBC 的一种方法。放射增敏剂可以减轻 RT 的不良反应。从植物等生物来源中提取绿色合成的银纳米粒子(Ag-NPs)毒性低,是使癌细胞对放疗敏感的潜在策略。因此,寻找新的天然来源来合成稳定而广泛适用的绿色银纳米粒子在癌症治疗中越来越受到关注。在本研究中,我们从南瓜皮提取物中合成了绿色Ag-NPs,并阐明了绿色Ag-NPs作为放射增敏剂对MDA-MB 231细胞(TNBC模型)的影响。制备的 Ag-NPs 呈球形,平均尺寸为 81 nm,zeta 电位为 - 9.96 mV。将绿色合成的 Ag-NPs 与 RT 结合使用可在 MDA-MB-231 细胞中发挥协同抗癌作用,最佳结合指数(CI)为 0.49。与相应的单一疗法相比,绿色合成的 Ag-NPs 能协同增强 RT 诱导的 MDA-MB-231 细胞凋亡。DAPI-TUNEL 染色试验进一步证实了细胞凋亡的形态学特征。接受联合疗法的细胞中,HIF-1α的表达减少。Bax和p53表达增加,而Bcl-2基因减少。与单一疗法相比,联合疗法明显提高了 PERK 和 CHOP 的蛋白水平,同时降低了细胞周期蛋白 D1 和 p-ERK/ 总 ERK 水平。这些研究结果表明,绿色合成的Ag-NPs可作为一种放射增敏剂用于TNBC治疗。
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来源期刊
Cancer Nanotechnology
Cancer Nanotechnology Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
5.20
自引率
1.80%
发文量
37
审稿时长
15 weeks
期刊介绍: Aim: Recognizing cancer as a group of diseases caused by nanostructural problems (i.e. with DNA) and also that there are unique benefits to approaches inherently involving nanoscale structures and processes to treat the disease, the journal Cancer Nanotechnology aims to disseminate cutting edge research; to promote emerging trends in the use of nanostructures and the induction of nanoscale processes for the prevention, diagnosis, treatment of cancer; and to cover related ancillary areas. Scope: Articles describing original research in the use of nanostructures and the induction of nanoscale processes for the prevention, diagnosis and treatment of cancer (open submission process). Review, editorial and tutorial articles picking up on subthemes of emerging importance where nanostructures and the induction of nanoscale processes are used for the prevention, diagnosis and treatment of cancer.
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