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

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.