依托泊苷-氧化石墨烯纳米凝胶增强乳腺癌治疗效果:一种新型纳米医学方法。
Enhanced efficacy of breast cancer treatment with etoposide-graphene oxide nanogels: A novel nanomedicine approach.
作者信息
Asoudeh-Fard Abbas, Mohkam Milad, Parsaei Asghar, Asghari Shadi, Lauto Antonio, Khoshnoudi Fatemeh, Al-Mamoori Mustafa Mhmood Salman, Asoudeh-Fard Mohadeseh, Ghasemi Sadabadi Hossine, Gholami Ahmad
机构信息
Institute Galilée-University Sorbonne, University Sorbonne Paris North, Paris, France.
Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran.
出版信息
Bioimpacts. 2025 Jun 25;15:30848. doi: 10.34172/bi.30848. eCollection 2025.
INTRODUCTION
Breast cancer represents a significant global health challenge, underscoring the need for innovative therapeutic strategies. This study explores the therapeutic potential of etoposide (ETO)-loaded graphene oxide (GO) nanogels to enhance the efficacy of breast cancer treatments.
METHODS
ETO-GO nanogels were synthesized and characterized using field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), and Fourier-transform infrared spectroscopy (FT-IR). Cytotoxicity was evaluated through MTT assays on MCF-7 breast cancer cells and normal HUVEC cells. Apoptosis induction was assessed using DAPI staining, flow cytometry, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to analyze changes in gene expression.
RESULTS
Characterization confirmed the formation of uniform, spherical nanogels with high ETO encapsulation efficiency. EDS and FT-IR analyses validated the successful loading of the drug onto the GO matrix. Cytotoxicity assays revealed a dose-dependent response, with significantly stronger effects observed in MCF-7 cells (20% viability at 100 µg/mL) than HUVEC cells (40% viability at the same concentration), indicating selective cytotoxicity. Apoptosis was verified through DAPI staining, which showed characteristics of nuclear fragmentation, and flow cytometry, identifying 15.35% of the treated cells as apoptotic. qRT-PCR analysis demonstrated an upregulation of pro-apoptotic genes (CASP3, CASP8, CASP9, BAX, PTEN) by as much as 8.3-fold, alongside a marked downregulation of the anti-apoptotic gene Bcl-2, confirming the potent induction of apoptosis by the nanogels.
CONCLUSION
ETO-GO nanogels show promising potential for targeted breast cancer therapy, providing enhanced drug delivery and selective cytotoxicity. These findings warrant further in vivo studies to validate their clinical applicability.
引言
乳腺癌是一项重大的全球健康挑战,凸显了创新治疗策略的必要性。本研究探讨了负载依托泊苷(ETO)的氧化石墨烯(GO)纳米凝胶在增强乳腺癌治疗效果方面的治疗潜力。
方法
采用场发射扫描电子显微镜(FE-SEM)、透射电子显微镜(TEM)、X射线衍射(XRD)、能量色散X射线光谱(EDS)和傅里叶变换红外光谱(FT-IR)对ETO-GO纳米凝胶进行合成和表征。通过MTT法对MCF-7乳腺癌细胞和正常HUVEC细胞进行细胞毒性评估。使用DAPI染色、流式细胞术和定量逆转录聚合酶链反应(qRT-PCR)评估凋亡诱导情况,以分析基因表达的变化。
结果
表征证实形成了具有高ETO包封效率的均匀球形纳米凝胶。EDS和FT-IR分析验证了药物成功负载到GO基质上。细胞毒性试验显示出剂量依赖性反应,在MCF-7细胞中观察到的效果(100μg/mL时存活率为20%)明显强于HUVEC细胞(相同浓度下存活率为40%),表明具有选择性细胞毒性。通过DAPI染色证实了凋亡,其显示出核碎片化特征,流式细胞术鉴定出15.35%的处理细胞为凋亡细胞。qRT-PCR分析表明促凋亡基因(CASP3、CASP8、CASP9、BAX、PTEN)上调高达8.3倍,同时抗凋亡基因Bcl-2明显下调,证实了纳米凝胶对凋亡的有效诱导。
结论
ETO-GO纳米凝胶在靶向乳腺癌治疗方面显示出有前景的潜力,提供了增强的药物递送和选择性细胞毒性。这些发现值得进一步进行体内研究以验证其临床适用性。
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