Glioblastoma multiforme (GBM) is the most malignant primary brain tumor of the central nervous system. Despite advances in therapy, it remains largely untreatable, in part due to the low permeability of chemotherapeutic drugs across the blood-brain barrier (BBB) which significantly compromises their effectiveness. To circumvent the lack of drug efficiency, we designed multifunctional nanoparticles based on porous silicon. Herein, we propose an innovative synthesis technique for porous silicon nanorods (pSiNRs) with three-dimensional (3D) shape-controlled nanostructure. In order to achieve an efficient administration and improved treatment against GBM cells, a porous silicon nanoplatform is designed with magnetic guidance, fluorescence tracking and a cell-penetrating peptide (CPP). A NeuroFilament Light (NFL) subunit derived 24 amino acid tubulin binding site peptide called NFL-TBS.40-63 peptide or NFL-peptide was reported to preferentially target human GBM cells compared to healthy cells. Motivated by this approach, we investigated the use of magnetic-pSiNRs covered with superparamagnetic iron oxide nanoparticles (SPIONs) for magnetic guidance, then decorated with the NFL-peptide to facilitate targeting and enhance internalization into human GBM cells. Unexpectedly, under confocal microscope imaging, the internalized multifunctional nanoparticles in GBM cells induce a remarkable exaltation of green fluorescence instead of the red native fluorescence from the dye due to a possible Förster resonance energy transfer (FRET). In addition, we showed that the uptake of NFL-peptide decorated magnetic-pSiNRs was preferential towards human GBM cells. This study presents the fabrication of magnetic-pSiNRs decorated with the NFL-peptide, which act as a remarkable candidate to treat brain tumors. This is supported by results and confocal imaging.
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http://dx.doi.org/10.1039/d2ra00508e | DOI Listing |
Med Chem
January 2025
Department of Chemistry, Faculty of Education, Van Yüzüncü Yil University, Van, Türkiye.
Background: Glioblastoma Multiforme (GBM), a highly aggressive and prevalent brain cancer with a higher incidence in males, has limited treatment success due to drug resistance, inadequate targeting and penetration of cancer cells, and an incomplete understanding of its molecular pathways. GBM is a highly aggressive brain cancer with limited treatment options. This study investigates the anticancer potential of synthesized pyrazole compounds against GBM cells.
View Article and Find Full Text PDFCommun Biol
January 2025
Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, PR China.
Almost all high-grade gliomas, particularly glioblastoma (GBM), are highly migratory and aggressive. Migrasomes are organelles produced by highly migratory cells capable of mediating intercellular communication. Thus, GBM cells may produce migrasomes during migration.
View Article and Find Full Text PDFCell Mol Life Sci
January 2025
Experimental Neurosurgery, Department of Neurosurgery, Neuroscience Center, Goethe University Hospital, Goethe University Frankfurt, 60528, Frankfurt am Main, Germany.
Glioblastoma (GBM), the most malignant primary brain tumor in adults, has poor prognosis irrespective of therapeutic advances due to its radio-resistance and infiltrative growth into brain tissue. The present study assessed functions and putative druggability of BRCA1-associated ATM activator 1 (BRAT1) as a crucial factor driving key aspects of GBM, including enhanced DNA damage response and tumor migration. By a stable depletion of BRAT1 in GBM and glioma stem-like (GSC) cell lines, we observed a delay in DNA double-strand break repair and increased sensitivity to radiation treatment, corroborated by in vitro and in vivo studies demonstrating impaired tumor growth and invasion.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Glioblastoma (GBM) is highly malignant and grows rapidly, and there is currently a lack of effective treatments. Metabolism provides the basis for the occurrence and development of GBM. Pyruvate dehydrogenase A1 (PDHA1) is a key component in both the tricarboxylic acid cycle and glycolysis, playing an important role in the metabolic processes related to cancer, but its role in GBM remains unclear.
View Article and Find Full Text PDFIndoleamine 2,3-dioxygenase 1 (IDO1) is a potently immunosuppressive protein that inhibits antitumor immunity through both tryptophan metabolism and non-enzymatic functions. Pharmacological therapies targeting IDO1 enzyme activity have generally failed to improve the overall survival of patients with cancer. Developing new therapeutic agents that are capable of neutralizing both enzyme-and non-enzyme-derived immunosuppressive IDO1 effects is therefore of high interest.
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