More Precise Mapping of Gliobalstoma Based on a Nanoprobe-Decorated Drug Molecule

Document Type : Hypothesis

Authors

1 Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Neuroscience and addiction studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Glioblastoma is considered as the most aggressive type of gliomas. Its invasive character involves adjacent tissues and hinders the treatment procedure. Although surgical resection followed by radiotherapy and chemotherapy have been the standard therapeutic protocol, the incompetency of detection methods to delineate the exact tumor margins results in recurrence of the tumor. NKCC1 (Sodium-Potassium-Chloride Cotransporter) is a transmembrane channel, which overexpress in pathological conditions like glioma and helps the tumor cells to change their shape for easier migration. Such a channel can play the role of a specific marker for infiltrating tumor cells and using a paired moiety against this transporter may possibly improve the precision of detection methods including Magnetic Resonance Imaging (MRI) contrast agents like SPNs (Superparamagnetic nanoparticles). Bumetanide, under the trade name of Bumex, is a diuretic drug that can block NKCC1. It has been demonstrated that in in-vivo context, bumetanide have the potency to decrease the migration of glioma cells. We have hypothesized that bumetanide can pair with NKCC1 and accumulate around the glioma cells. Hence, it seems that MRI contrast agents loaded with bumex on their surface can be proposed for more accurate tumor margins detection whilst providing additional therapeutic effects. The proposed theranostic nanostructure may further be improved and tested both in-vitro and in-vivo to prove its applicability.

Keywords


  1. Louis DN. Molecular pathology of malignant gliomas. Annu Rev Pathol Mech Dis. 2006;1:97-117.http://dx.doi.org/10.1146/annurev.pathol.1.110304.100043
  2. Verkhratsky A, Butt AM. Glial neurobiology: John Wiley & Sons; 2007.
  3. Lemasson B, Galban CJ, Boes JL, Li Y, Zhu Y, Heist KA, et al. Diffusion-Weighted MRI as a Biomarker of Tumor Radiation Treatment Response Heterogeneity: A Comparative Study of Whole-Volume Histogram Analysis versus Voxel-Based Functional Diffusion Map Analysis. Transl Oncol. 2013;6(5):554-61.http://dx.doi.org/10.1593/tlo.13532
  4. Deviers A, Ken S, Filleron T, Rowland B, Laruelo A, Catalaa I, et al. Evaluation of the lactate-to-N-acetyl-aspartate ratio defined with magnetic resonance spectroscopic imaging before radiation therapy as a new predictive marker of the site of relapse in patients with glioblastoma multiforme. Int J Radiat Oncol Biol Phys. 2014;90(2):385-93. Epub 2014/08/12.http://dx.doi.org/10.1016/j.ijrobp.2014.06.009
  5. Lassman AB. Molecular biology of gliomas. Current neurology and neuroscience reports. 2004;4(3):228-33.http://dx.doi.org/10.1007/s11910-004-0043-3
  6. Unkelbach J, Menze BH, Konukoglu E, Dittmann F, Ayache N, Shih HA. Radiotherapy planning for glioblastoma based on a tumor growth model: implications for spatial dose redistribution. Phys Med Biol. 2014;59(3):771.http://dx.doi.org/10.1088/0031-9155/59/3/747
  7. Giese A, Loo MA, Tran N, Haskett D, Coons SW, Berens ME. Dichotomy of astrocytoma migration and proliferation. Int J Cancer. 1996;67(2):275-82.http://dx.doi.org/10.1002/(SICI)1097-0215(19960717)67:23.0.CO;2-9
  8. Lauffenburger DA, Horwitz AF. Cell migration: a physically integrated molecular process. Cell. 1996;84(3):359-69.http://dx.doi.org/10.1016/S0092-8674(00)81280-5
  9. Haas BR, Sontheimer H. Inhibition of the sodium-potassium-chloride cotransporter isoform-1 reduces glioma invasion. Cancer Res. 2010;70(13):5597-606.http://dx.doi.org/10.1158/0008-5472.CAN-09-4666
  10. Mercado A, Mount DB, Gamba G. Electroneutral cation-chloride cotransporters in the central nervous system. Neurochem Res. 2004;29(1):17-25.http://dx.doi.org/10.1023/B:NERE.0000010432.44566.21
  11. Kaplan MR, Mount DB, Delpire E, Gamba G, Hebert SC. Molecular mechanisms of NaCl cotransport. Annu Rev Physiol. 1996;58(1):649-58.http://dx.doi.org/10.1146/annurev.ph.58.030196.003245
  12. Becker M, Nothwang HG, Friauf E. Differential expression pattern of chloride transporters NCC, NKCC2, KCC1, KCC3, KCC4, and AE3 in the developing rat auditory brainstem. Cell Tissue Res. 2003;312(2):155-65.http://dx.doi.org/10.1007/s00441-003-0713-5
  13. Raouf R, Quick K, Wood JN. Pain as a channelopathy. J Clinical Invest. 2010;120(11):3745.http://dx.doi.org/10.1172/JCI43158
  14. Chen H, Sun D. The role of Na–K–Cl co–transporter in cerebral ischemia. Neurol Res. 2005;27(3):280-6.http://dx.doi.org/http://dx.doi.org/10.1179/016164105X25243
  15. Ernest NJ, Sontheimer H. Extracellular glutamine is a critical modulator for regulatory volume increase in human glioma cells. Brain Res. 2007;1144:231-8.http://dx.doi.org/10.1016/j.brainres.2007.01.085
  16. Habela CW, Ernest NJ, Swindall AF, Sontheimer H. Chloride accumulation drives volume dynamics underlying cell proliferation and migration. J Neurophysiol. 2009;101(2):750-7.http://dx.doi.org/10.1152/jn.90840.2008
  17. Garzon-Muvdi T, Schiapparelli P, ap Rhys C, Guerrero-Cazares H, Smith C, Kim D-H, et al. Regulation of brain tumor dispersal by NKCC1 through a novel role in focal adhesion regulation. PLoS Biol. 2012;10(5):1070.http://dx.doi.org/10.1371/journal.pbio.1001320
  18. Gamba G. Molecular physiology and pathophysiology of electroneutral cation-chloride cotransporters. Physiol Rev. 2005;85(2):423-93.http://dx.doi.org/10.1152/physrev.00011.2004
  19. Eftekhari S, Mehvari Habibabadi J, Najafi Ziarani M, Hashemi Fesharaki SS, Gharakhani M, Mostafavi H, et al. Bumetanide reduces seizure frequency in patients with temporal lobe epilepsy. Epilepsia. 2013;54(1):9-12.http://dx.doi.org/10.1111/j.1528-1167.2012.03654.x
  20. Wu W, Wu Z, Yu T, Jiang C, Kim W-S. Recent progress on magnetic iron oxide nanoparticles: synthesis, surface functional strategies and biomedical applications. Sci Technol Adv Mater. 2015;16(2):023501.http://dx.doi.org/10.1088/1468-6996/16/2/023501
  21. Benz M. Superparamagnetism: theory and applications. Discussion. 2012.
  22. Singh N, Jenkins GJ, Asadi R, Doak SH. Potential toxicity of superparamagnetic iron oxide nanoparticles (SPION). Nano Rev. 2010;1.http://dx.doi.org/10.3402/nano.v1i0.5358
  23. Weissleder R, Nahrendorf M, Pittet MJ. Imaging macrophages with nanoparticles. Nature Mater. 2014;13(2):125-38.http://dx.doi.org/10.1038/nmat3780
  24. Wang Y, Ng YW, Chen Y, Shuter B, Yi J, Ding J, et al. Formulation of superparamagnetic iron oxides by nanoparticles of biodegradable polymers for magnetic resonance imaging. Adv Funct Mater. 2008;18(2):308-18.http://dx.doi.org/10.1002/adfm.200700456
  25. Kohler N, Sun C, Wang J, Zhang M. Methotrexate-modified superparamagnetic nanoparticles and their intracellular uptake into human cancer cells. Langmuir. 2005;21(19):8858-64.http://dx.doi.org/10.1021/la0503451
  26. Lu J, Liong M, Li Z, Zink JI, Tamanoi F. Biocompatibility, Biodistribution, and Drug‐Delivery Efficiency of Mesoporous Silica Nanoparticles for Cancer Therapy in Animals. Small. 2010;6(16):1794-805.http://dx.doi.org/10.1002/smll.201000538