ae00e03cba33df16ef47f09c3e453370 pmc_34576098.pdf c04627ec953676057866374ec5db863c57fadaac pmc_34576098.pdf c89686648e860f9684ce4bcd7146aef8e7f9adeb014d846261c9f62789d82b2e pmc_34576098.pdf Title: Synchrotron-Based Fourier-Transform Infrared Micro-Spectroscopy (SR-FTIRM) Fingerprint of the Small Anionic Molecule Cobaltabis(dicarbollide) Uptake in Glioma Stem Cells Subject: The anionic cobaltabis (dicarbollide) [3,3'-Co(1,2-C2B9H11)2]-, [o-COSAN]-, is the most studied icosahedral metallacarborane. The sodium salts of [o-COSAN]- could be an ideal candidate for the anti-cancer treatment Boron Neutron Capture Therapy (BNCT) as it possesses the ability to readily cross biological membranes thereby producing cell cycle arrest in cancer cells. BNCT is a cancer therapy based on the potential of 10B atoms to produce particles that cross tissues in which the 10B is accumulated without damaging the surrounding healthy tissues, after being irradiated with low energy thermal neutrons. Since Na[o-COSAN] displays a strong and characteristic (B-H) frequency in the infrared range 2.600–2.500 cm-1, we studied the uptake of Na[o-COSAN] followed by its interaction with biomolecules and its cellular biodistribution in two different glioma initiating cells (GICs), mesenchymal and proneural respectively, by using Synchrotron Radiation-Fourier Transform Infrared (FTIR) micro-spectroscopy (SR-FTIRM) facilities at the MIRAS Beamline of ALBA synchrotron light source. The spectroscopic data analysis from the bands in the regions of DNA, proteins, and lipids permitted to suggest that after its cellular uptake, Na[o-COSAN] strongly interacts with DNA strings, modifies proteins secondary structure and also leads to lipid saturation. The mapping suggests the nuclear localization of [o-COSAN]-, which according to reported Monte Carlo simulations may result in a more efficient cell-killing effect compared to that in a uniform distribution within the entire cell. In conclusion, we show pieces of evidence that at low doses, [o-COSAN]- translocates GIC cells’ membranes and it alters the physiology of the cells, suggesting that Na[o-COSAN] is a promising agent to BNCT for glioblastoma cells. Keywords: boron neutron capture therapy; cobaltabis(dicarbollide); DNA interactions; glioblastoma; glioma initiating cells; inorganic small molecules; lipid saturation; SR-FTIRM Author: Miquel Nuez-Martínez, Leire Pedrosa, Immaculada Martinez-Rovira, Ibraheem Yousef, Diouldé Diao, Francesc Teixidor, Elisabetta Stanzani, Fina Martínez-Soler, Avelina Tortosa, Àngels Sierra, José Juan Gonzalez and Clara Viñas Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Sep 15 16:29:04 2021 CEST ModDate: Wed Sep 15 16:36:54 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 25 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 6961255 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- YQMKHR+VnURWPalladioL Type 1 Custom yes yes no 10 0 TTRXFO+EURM10 Type 1 Builtin yes yes no 15 0 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1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 500 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Results and Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: o-Cobaltabis(Dicarbollide), [o-COSAN]- Uptake Induces Glioma Initiating Cells (GICs) Phenotypic Changes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: GICs Na[o-COSAN] Uptake Analysis by SR-FTIRM and Multivariate Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Children: Item: Title: SR-FTIRM at the DNA Region Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: SR-FTIRM at the Region of the Protein Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: SR-FTIRM at the Lipids Region Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Na[o-COSAN] Induces DNA, Proteins, and Lipids Changes on GICs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Children: Item: Title: Reagents Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Chemistry Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Cell Culture and Treatments Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Samples Preparation for SR-FTIRM Measurements Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: SR-FTIRM Measurements Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: FTIRM Software & Data Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Kinetic Assay Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: PrestoBlue Assay Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Cytotoxicity and Half Maximal Effect Concentration (EC50) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Cell Cycle Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Microscopic Observations of Cell Morphology Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Info: Title: Synchrotron-Based Fourier-Transform Infrared Micro-Spectroscopy (SR-FTIRM) Fingerprint of the Small Anionic Molecule Cobaltabis(dicarbollide) Uptake in Glioma Stem Cells Author: Miquel Nuez-Martínez, Leire Pedrosa, Immaculada Martinez-Rovira, Ibraheem Yousef, Diouldé Diao, Francesc Teixidor, Elisabetta Stanzani, Fina Martínez-Soler, Avelina Tortosa, Àngels Sierra, José Juan Gonzalez and Clara Viñas Subject: The anionic cobaltabis (dicarbollide) [3,3'-Co(1,2-C2B9H11)2]-, [o-COSAN]-, is the most studied icosahedral metallacarborane. The sodium salts of [o-COSAN]- could be an ideal candidate for the anti-cancer treatment Boron Neutron Capture Therapy (BNCT) as it possesses the ability to readily cross biological membranes thereby producing cell cycle arrest in cancer cells. BNCT is a cancer therapy based on the potential of 10B atoms to produce particles that cross tissues in which the 10B is accumulated without damaging the surrounding healthy tissues, after being irradiated with low energy thermal neutrons. Since Na[o-COSAN] displays a strong and characteristic (B-H) frequency in the infrared range 2.600 2.500 cm-1, we studied the uptake of Na[o-COSAN] followed by its interaction with biomolecules and its cellular biodistribution in two different glioma initiating cells (GICs), mesenchymal and proneural respectively, by using Synchrotron Radiation-Fourier Transform Infrared (FTIR) micro-spectroscopy (SR-FTIRM) facilities at the MIRAS Beamline of ALBA synchrotron light source. The spectroscopic data analysis from the bands in the regions of DNA, proteins, and lipids permitted to suggest that after its cellular uptake, Na[o-COSAN] strongly interacts with DNA strings, modifies proteins secondary structure and also leads to lipid saturation. The mapping suggests the nuclear localization of [o-COSAN]-, which according to reported Monte Carlo simulations may result in a more efficient cell-killing effect compared to that in a uniform distribution within the entire cell. In conclusion, we show pieces of evidence that at low doses, [o-COSAN]- translocates GIC cells’ membranes and it alters the physiology of the cells, suggesting that Na[o-COSAN] is a promising agent to BNCT for glioblastoma cells. Keywords: boron neutron capture therapy; cobaltabis(dicarbollide); DNA interactions; glioblastoma; glioma initiating cells; inorganic small molecules; lipid saturation; SR-FTIRM Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Sep 15 16:29:04 CEST 2021 ModDate: Wed Sep 15 16:36:54 CEST 2021 ID: 0x19493e6df51a1c627219fba3fe1cdcf8, 0x19493e6df51a1c627219fba3fe1cdcf8 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: HCTBNX+CMSY10 FontSubset: true FirstChar: 0 LastChar: 48 FontDescriptor: FontName: HCTBNX+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: WUFLJI+CMEX10 FontSubset: true FirstChar: 82 LastChar: 82 FontDescriptor: FontName: WUFLJI+CMEX10 Flags: Symbolic FontBBox: -24, -2960, 1454, 772 FontFile: true Font: BaseFont: YAYPHP+URWPalladioL-Ital FontSubset: true FirstChar: 38 LastChar: 121 FontDescriptor: FontName: YAYPHP+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true 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Rect: 218, 192, 255, 203 Checksum: f683e137 Type: CRC32 Checksum: ae00e03cba33df16ef47f09c3e453370 Type: MD5 Checksum: c04627ec953676057866374ec5db863c57fadaac Type: SHA-1