Identification of indirect pathways enhancing the biocompatibility of DOX/GO/Fe3O4 nanomaterials in Glioblastoma: Gene network modeling and pathway analysis

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications Pub Date : 2025-05-26 DOI:10.1016/j.bbrc.2025.152077

Amin Alvani , Negar Mottaghi-Dastjerdi , Ahmad Gholami , Abozar Ghorbani , Zeinab Pazhoohesh , Mohammad Pajdam , Ali Eskanderi , Mohammad-Javad Niazi

{"title":"Identification of indirect pathways enhancing the biocompatibility of DOX/GO/Fe3O4 nanomaterials in Glioblastoma: Gene network modeling and pathway analysis","authors":"Amin Alvani , Negar Mottaghi-Dastjerdi , Ahmad Gholami , Abozar Ghorbani , Zeinab Pazhoohesh , Mohammad Pajdam , Ali Eskanderi , Mohammad-Javad Niazi","doi":"10.1016/j.bbrc.2025.152077","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Glioblastoma multiforme (GBM) is the most common primary malignant tumor of the central nervous system. Conventional treatment includes maximal safe surgical resection combined with radiotherapy and chemotherapy.</div></div><div><h3>Materials and methods</h3><div>This study analyzed gene networks to identify key gene clusters and hub genes involved in apoptosis using Cytoscape in Glioblastoma cell line samples treated with GO/Fe<sub>3</sub>O<sub>4</sub> and DOX/GO/Fe<sub>3</sub>O<sub>4</sub> for 24 h. The cytotoxicity of DOX on A-172 cells was assessed using the MTT assay. Real-time PCR was used to evaluate the expression of Casp3, Bcl-2, and BAX genes in A-172 cells treated with free DOX and DOX-loaded GO/Fe<sub>3</sub>O<sub>4</sub> (DOX/GO/Fe<sub>3</sub>O<sub>4</sub>).</div></div><div><h3>Result</h3><div>the IC50 values for free DOX and DOX/GO/Fe<sub>3</sub>O<sub>4</sub> were determined to be 80 μg/mL and 40 μg/mL, respectively. Real-time PCR analysis revealed that both DOX/GO/Fe<sub>3</sub>O<sub>4</sub> and free DOX upregulated the expression of Casp3 and Bax genes, with minimal changes observed in Bcl-2 expression in A-172 cells. Bioinformatic analysis using NetworkAnalyst's \"Mapping Overview\" indicated that miR-92a-2-5p is a potential therapeutic target for preventing myocardial damage and enhancing the biocompatibility of DOX/GO/Fe<sub>3</sub>O<sub>4</sub> in GBM. Furthermore, conditions of cancer cells showed similarities to embryonic cells, with involvement in thermogenesis (miR-143), absorption by vascular endothelial cells, increased angiogenesis (miR-135ab/135a-5p), axon regeneration (miR-7/7 ab), and regulation of circadian rhythm, aging, oxidative stress, mitochondrial dysfunction, and neuroinflammation.</div></div><div><h3>Conclusion</h3><div>Bioinformatic analysis suggests that autophagy-regulating nanomaterials and their incorporation into nano-complexes can enhance the biocompatibility of DOX/GO/Fe<sub>3</sub>O<sub>4</sub>. The nanocomplex's pH sensitivity prolongs drug exposure in GBM, and targeting GBM with an external magnetic field presents a promising approach for GBM treatment.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"773 ","pages":"Article 152077"},"PeriodicalIF":2.5000,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemical and biophysical research communications","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0006291X25007910","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Glioblastoma multiforme (GBM) is the most common primary malignant tumor of the central nervous system. Conventional treatment includes maximal safe surgical resection combined with radiotherapy and chemotherapy.

Materials and methods

This study analyzed gene networks to identify key gene clusters and hub genes involved in apoptosis using Cytoscape in Glioblastoma cell line samples treated with GO/Fe₃O₄ and DOX/GO/Fe₃O₄ for 24 h. The cytotoxicity of DOX on A-172 cells was assessed using the MTT assay. Real-time PCR was used to evaluate the expression of Casp3, Bcl-2, and BAX genes in A-172 cells treated with free DOX and DOX-loaded GO/Fe₃O₄ (DOX/GO/Fe₃O₄).

Result

the IC50 values for free DOX and DOX/GO/Fe₃O₄ were determined to be 80 μg/mL and 40 μg/mL, respectively. Real-time PCR analysis revealed that both DOX/GO/Fe₃O₄ and free DOX upregulated the expression of Casp3 and Bax genes, with minimal changes observed in Bcl-2 expression in A-172 cells. Bioinformatic analysis using NetworkAnalyst's "Mapping Overview" indicated that miR-92a-2-5p is a potential therapeutic target for preventing myocardial damage and enhancing the biocompatibility of DOX/GO/Fe₃O₄ in GBM. Furthermore, conditions of cancer cells showed similarities to embryonic cells, with involvement in thermogenesis (miR-143), absorption by vascular endothelial cells, increased angiogenesis (miR-135ab/135a-5p), axon regeneration (miR-7/7 ab), and regulation of circadian rhythm, aging, oxidative stress, mitochondrial dysfunction, and neuroinflammation.

Conclusion

Bioinformatic analysis suggests that autophagy-regulating nanomaterials and their incorporation into nano-complexes can enhance the biocompatibility of DOX/GO/Fe₃O₄. The nanocomplex's pH sensitivity prolongs drug exposure in GBM, and targeting GBM with an external magnetic field presents a promising approach for GBM treatment.

查看原文本刊更多论文

增强DOX/GO/Fe3O4纳米材料在胶质母细胞瘤中生物相容性的间接途径的鉴定：基因网络建模和途径分析

多形性胶质母细胞瘤（GBM）是最常见的中枢神经系统原发性恶性肿瘤。常规治疗包括最大限度的安全手术切除联合放化疗。材料和方法本研究利用Cytoscape分析了胶质母细胞瘤细胞系样品中氧化石墨烯/氧化石墨烯/氧化石墨烯/氧化石墨烯/氧化石墨烯/氧化石墨烯/氧化石墨烯/氧化石墨烯处理24小时的基因网络，以确定参与细胞凋亡的关键基因簇和枢纽基因。Real-time PCR检测游离DOX和负载DOX的GO/Fe3O4 （DOX/GO/Fe3O4）处理的A-172细胞中Casp3、Bcl-2和BAX基因的表达情况。结果测定游离DOX和DOX/GO/Fe3O4的IC50值分别为80 μg/mL和40 μg/mL。实时PCR分析显示，DOX/GO/Fe3O4和游离DOX均上调了A-172细胞中Casp3和Bax基因的表达，而Bcl-2的表达变化很小。使用NetworkAnalyst的“Mapping Overview”进行的生物信息学分析表明，miR-92a-2-5p是预防心肌损伤和增强DOX/GO/Fe3O4在GBM中的生物相容性的潜在治疗靶点。此外，癌细胞的情况与胚胎细胞相似，参与产热（miR-143）、血管内皮细胞的吸收、血管生成（miR-135ab/135a-5p）、轴突再生（mir -7/ 7ab）、昼夜节律、衰老、氧化应激、线粒体功能障碍和神经炎症的调节。结论生物信息学分析表明，自噬调节纳米材料及其掺入纳米复合物可增强DOX/GO/Fe3O4的生物相容性。纳米复合物的pH敏感性延长了药物在GBM中的暴露时间，用外磁场靶向GBM是治疗GBM的一种很有前途的方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Biochemical and biophysical research communications 生物-生化与分子生物学

CiteScore

6.10

自引率

0.00%

发文量

1400

审稿时长

14 days

期刊介绍： Biochemical and Biophysical Research Communications is the premier international journal devoted to the very rapid dissemination of timely and significant experimental results in diverse fields of biological research. The development of the "Breakthroughs and Views" section brings the minireview format to the journal, and issues often contain collections of special interest manuscripts. BBRC is published weekly (52 issues/year).Research Areas now include: Biochemistry; biophysics; cell biology; developmental biology; immunology ; molecular biology; neurobiology; plant biology and proteomics