Microdistribution and quantification of the boron neutron capture therapy drug BPA in primary cell cultures of human glioblastoma tumour by NanoSIMS
| Autor: | G. McMahon, Nicholas P. Lockyer, Samar Aldossari, Katie L. Moore |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Boron Compounds
ResearchInstitutes_Networks_Beacons/photon_science_institute Phenylalanine Cell Intracellular Space Boron Neutron Capture Therapy 02 engineering and technology Photon Science Institute 01 natural sciences Biochemistry Mass Spectrometry Analytical Chemistry Drug distribution Cell Line Tumor Electrochemistry medicine Environmental Chemistry Distribution (pharmacology) Humans Nanotechnology glioblastoma multiform Spectroscopy Chemistry Brain Neoplasms 010401 analytical chemistry 1OB-BPA 021001 nanoscience & nanotechnology 0104 chemical sciences Molecular Imaging medicine.anatomical_structure boron neutral capture therapy Cytoplasm Cell culture Cancer cell Cancer research BNCT Efflux Molecular imaging 0210 nano-technology Glioblastoma SIMS Intracellular |
| Zdroj: | Aldossari, S, Mcmahon, G, Lockyer, N & Moore, K 2019, ' Microdistribution and quantification of the boron neutron capture therapy drug BPA in primary cell cultures of human glioblastoma tumour by NanoSIMS ', The Analyst . https://doi.org/10.1039/C9AN01336A |
| Popis: | The ability of secondary ion mass spectrometry (SIMS) to provide high sensitivity imaging of elements and small-medium mass molecules in biological tissues and cells, makes it a very powerful tool for drug distribution studies. Here we report on the application of a high resolution dynamic SIMS instrument for the quantification and localisation of therapeutic levels of the BNCT agent L-para-(dihydroxyboryl)-phenylalanine (BPA) in primary cell cultures from human patients exhibiting glioblastoma multiform tumours. Boron uptake and distribution was determined quantitatively as a function of cell-sampling location and different treatment regimes. Importantly, BPA was found to accumulate in cancer cells invading the ‘brain around tumour’ tissue in addition to the main tumour site. Pre treatment of samples with L-tyrosine was found not to increase the uptake of BPA, nor change the intracellular drug distribution. In cultured cells from the tumour core and brain around tumour, with and without L-tyrosine pre-treatment, normalised boron-related signals were higher from cell nuclei than from cytoplasm. An efflux treatment was found to reduce BPA levels, but at a rate slower than the original uptake, and did not affect the intracellular drug distribution. To the best of our knowledge, these data represent the first published study of BPA uptake and L-amino acid pre-treatment in cultured primary human cells using dynamic SIMS, and the most detailed, subcellular distribution study of a BNCT agent in any cellular system. |
| Databáze: | OpenAIRE |
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