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.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27fc/12319212/fd548f705268/bi-15-30848-g001.jpg

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