Frederik Vernimmen^1*, Mikhail L. Shmatov²

Show more
¹ Department of Radiation Oncology, Cork University Hospital, Cork, Ireland.
² Ioffe Institute, St. Petersburg, Russia.
Show less

Abstract: Objective of the study: To explore the potential for therapeutic gain with gold nanoparticles in arteriovenous malformation radiosurgery based on their interaction with photons and protons. Study methods: Radiation dose enhancement resulting from the interaction of gold nanoparticles with irradiation ranging from kilovoltage to megavoltage photons and protons was researched in the literature. The role of angiogenesis and its regulation via vascular endothelial growth factors and cell membrane receptors, especially for endothelial cells in arteriovenous malformations, was investigated as a way for selective arteriovenous malformation deposition. Results: Radiation dose enhancement with gold nanoparticles is described in the literature but has so far only been investigated for its potential in treating malignancies. Because of the high atomic number of gold (Z = 79), dose enhancement occurs with photons mainly based on secondary photon and Auger electron production and the dose enhancement factor is the highest for irradiation with kilo voltage photons. Dose enhancement happens with megavoltage photons also but to a lesser extend and is mainly due to the ionization of gold by secondary photons and electrons generated by the megavoltage photons passing through tissue. The range of the secondary photo electrons emitted by gold is sufficient to cover the entire endothelial cell content. Protons interact with the production of Auger electrons which have a very short range, insufficient to cover the entire contents of endothelial cells, but sufficient to cause a high cell membrane dose for membrane located gold nanoparticles (AuNPs). Arteriovenous malformations are dynamic entities with angiogenesis taking place. This is reflected by a different expression of angiogenic receptors on the membrane of arteriovenous malformation endothelial cells compared to normal brain blood vessels, thereby opening the opportunity for selective deposition of such particles. For the use in proton therapy a new definition for the dose enhancement factor describing the local effect of nanoparticles is proposed. Conclusion: The concept of nanoparticle enhanced radiosurgery for arteriovenous malfor-mations by selective deposition of gold nanoparticles is a novel approach. The local dose enhancement opens the way for therapeutic gain which in turn could lead to improved obliteration rates and/or a shorter latent period.

Keywords: Nanoparticle, Arteriovenous Malformation, Radiosurgery, Dose Enhancement

Cite this paper: Vernimmen, F. and Shmatov, M. (2015) Gold Nanoparticles in Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations. Journal of Biomaterials and Nanobiotechnology, 6, 204-212. doi: 10.4236/jbnb.2015.63019.

References

[1]   Thakor, A.S., Jokerst, J., Zaveleta, C., Massoud, T.F. and Gambhir, S.S. (2011) Gold Nanoparticles: A Revival in Precious Metal Administration to Patients. Nano Letters, 11, 4029-4036.
http://dx.doi.org/10.1021/nl202559p

[2]   Mieszawska, A.J., Mulder, W.J.M., Fayad, Z.A. and Cormode, D.P. (2013) Multifunctional Gold Nanoparticles for Diagnosis and Therapy of Disease. Molecular Pharmaceutics, 10, 831-847.
http://dx.doi.org/10.1021/mp3005885

[3]   Babaei, M. and Ganjalikhani, M. (2014) A Systematic Review of Gold Nanoparticles as Novel Cancer Therapeutics. Nanomedicine Journal, 1, 211-219.

[4]   Cai, W.B., Gao, T., Hong, H. and Sun, J.T. (2008) Applications of Gold Nanoparticles in Cancer Nanotechnology. Nanotechnology, Science and Applications, 1, 17-32.

[5]   Kumar, R., Korideck, H., Ngwa, W., Berbeco, R.I. and Sridhar, S. (2013) Third Generation Gold Nanoplatform Optimized for Radiation Therapy. Translational Cancer Research, 2, 228-239.

[6]   Ngwa, W., Kumar, R., Sridhar, S., Korideck, H., Zygmanski, P., Cormack, R.A., et al. (2014) Targeted Radiotherapy with Gold Nanoparticles: Current Status and Future Perspectives. Nanomedicine, 9, 1063-1082.
http://dx.doi.org/10.2217/nnm.14.55

[7]   Hainfeld, J.F., Dilmanian, F.A., Slatkin, D.N. and Smilowitz, H.M. (2008) Radiotherapy Enhancement with Gold Nanoparticles. J Pharm Pharmacol, 60, 977-985.
http://dx.doi.org/10.1211/jpp.60.8.0005

[8]   Liu, C.J., Wang, C.H., Chen, S.T., Chen, H.H., Leng, W.H., Chien, C.C., et al. (2010) Enhancement of Cell Radiation Sensitivity by Pegylated Gold Nanoparticles. Physics in Medicine and Biology, 55, 931-945.
http://dx.doi.org/10.1088/0031-9155/55/4/002

[9]   Cooper, D.R., Bekah, D. and Nadeau, J.L. (2014) Gold Nanoparticles and Their Alternatives for Radiation Therapy Enhancement. Frontiers in Chemistry, 2, Article 86.
http://dx.doi.org/10.3389/fchem.2014.00086

[10]   Kwatra, D., Venugopal, A. and Anant, S. (2013) Nanoparticles in Radiation Therapy: A Summary of Various Approaches to Enhance Radiosensitization in Cancer. Translational Cancer research, 2, 330-342.

[11]   Kim, J.K., Seo, S.J., Kim, H.T., Kim, K.H., Chung, M.H., Kim, K.R., et al. (2012) Enhanced Proton Treatment in Mouse Tumours through Proton Irradiated Nanoradiator Effects on Metallic Nanoparticles. Physics in Medicine and Biology, 57, 8309-8323.
http://dx.doi.org/10.1088/0031-9155/57/24/8309

[12]   Babaei, M. and Ganjalikhani, M. (2014) The Potential Effectiveness of Nanoparticles as Radiosensitizers for Radiotherapy. Bioimpacts, 4, 15-20.

[13]   Kim, B.Y.S., Rutka, J.T. and Chan, W. (2010) Current Concepts Nanomedicine. New England Journal of Medicine, 363, 2434-2343.
http://dx.doi.org/10.1056/NEJMra0912273

[14]   Lin, Z., Monteiro-Riviere, N.A. and Riviere, J.E. (2015) Pharmacokinetics of Metallic Nanoparticles. Nanomed Nanobiotechnol, 7, 189-217.
http://dx.doi.org/10.1002/wnan.1304

[15]   Zhang, X. (2015) Gold Nanoparticles: Recent Advances in the Biomedical Applications. Cell Biochemistry and Biophysics, Epub ahead of publication.

[16]   Hossain, M. and Ming, S. (2012) Nanoparticle Location and Material Dependent Dose Enhancement in X-Ray Radiation Therapy. The Journal of Physical Chemistry C: Nanomater Interfaces, 116, 23047-23052.
http://dx.doi.org/10.1021/jp306543q

[17]   McMahon, S.J., Hyland, W.B., Muir, M.F., Coulter, J.A., Jain, S., Butterworth, K.T., et al. (2011) Nanodosimetric Effects of Gold Nanoparticles in Megavoltage Radiation Therapy. Radiotherapy and Oncology, 100, 412-416.
http://dx.doi.org/10.1016/j.radonc.2011.08.026

[18]   Berbeco, R.I., Ngwa, W. and Makrigiorgos, G. (2011) Localized Dose Enhancement to Tumour Blood Vessel Endothelial Cells via Megavoltage X-Rays and Targeted Gold Nanoparticles: New Potential for External Beam Radiotherapy. International Journal of Radiation Oncology, Biology, Physics, 81, 270-276.
http://dx.doi.org/10.1016/j.ijrobp.2010.10.022

[19]   Sicard-Roselli, C., Brun, E., Gilles, M., Baldacchino, G., Kelsey, C., McQuaid, H., et al. (2014) A New Mechanismfor Hydroxyl Radical Production in Irradiated Nanoparticle Solutions. Small, 10, 3338-3346.
http://dx.doi.org/10.1002/smll.201400110

[20]   Taggart, L.E., McMahon, S.J., Currell, F.J., Prise, K.M. and Butterworth, K.T. (2014) The Role of Mitochondrial Function in Gold Nanoparticle Mediated Radiosensitization. Cancer Nanotechnology, 5, 5.
http://dx.doi.org/10.1186/s12645-014-0005-7

[21]   Lin, Y., McMahon, S.J., Scarpelli, M., Paganetti, H. and Schuemann, J. (2014) Comparing Gold Nano-Particle Enhanced Radiotherapy with Protons, Megavoltage Photons and Kilovoltage Photons: A Monte Carlo Simulation. Physics in Medicine and Biology, 59, 7675-7689.
http://dx.doi.org/10.1088/0031-9155/59/24/7675

[22]   Wlzlein, C., Scifoni, E., Kramer, M. and Durante, M. (2014) Simulations of Dose Enhancement for Heavy Atom Nanoparticles Irradiated by Protons. Physics in Medicine and Biology, 59, 1441-1458.
http://dx.doi.org/10.1088/0031-9155/59/6/1441

[23]   Robar, J.L., Riccio, S.A. and Martin, M.A. (2002) Tumor Dose Enhancement Using Modified Megavoltage Photon Beams and Contrast Media. Physics in Medicine and Biology, 47, 2433-2449.
http://dx.doi.org/10.1088/0031-9155/47/14/305

[24]   Polf, J.C., Bronk, L.F., Driessen, W.H.P., Arap, W., Pasqualini, R. and Gillin, M. (2011) Enhanced Relative Biological Effectiveness of Proton Radiotherapy with Internalized Gold Nanoparticles. Applied Physics Letters, 98, Article ID: 193702.
http://dx.doi.org/10.1063/1.3589914

[25]   Le Sech, C., Kobayashi, K., Usami, N., Furusawa, Y., Porcel, E. and Lacombe, S. (2012) Comment on “Enhanced Relative Biological Effectiveness of Proton Radiotherapy in Tumor Cells with Internalized Gold Nanoparticles”. Applied Physics Letters, 100, Article ID: 026101.
http://dx.doi.org/10.1063/1.3675570

[26]   Samuel, A.H. and Magee, J.L. (1953) Theory of Radiation Chemistry. II. Track Effects in Radiolysis of Water. The Journal of Chemical Physics, 21, 1080-1087.
http://dx.doi.org/10.1063/1.1699113

[27]   Byakov, V.M. and Stepanov, S.V. (2006) The Mechanism for the Primary Biological Effect of Ionizing Radiation. Uspekhi Fizicheskikh Nauk, 176, 487-506. (English citation: Physics-Uspekhi, 49, 469-487)
http://dx.doi.org/10.3367/UFNr.0176.200605b.0487

[28]   Porcel, E., Liehn, S., Remitta, H., Usami, N., Kobayashi, K., Furusawa, Y., et al. (2010) Platinum Nanoparticles: A Promising Material for Future Cancer Therapy? Nanothechnology, 21, Article ID: 85103.
http://dx.doi.org/10.1088/0957-4484/21/8/085103

[29]   Brun, E., Sanche, L. and Sicard-Roselli, C. (2009) Parameters Governing Gold Nanoparticle X-Ray Radiosensitization of DNA in Solution. Colloids and Surfaces B: Biointerfaces, 72, 128-134.
http://dx.doi.org/10.1016/j.colsurfb.2009.03.025

[30]   Amato, E., Italiano, A., Leotta, S., Pergolizzi, S. and Torrise, L. (2013) Monte Carlo Study of the Dose Enhancement Effect of Gold Nanoparticles during X-Ray Therapies and Evaluation of the Anti-Angiogenic Effect on Tumour Capillary Vessels. Journal of X-Ray Science and Technology, 21, 237-247.

[31]   Detappe, A., Tsiamas, P. and Ngwa, W. (2013) The Effect of Flattening Filter Free Delivery on Endothelial Dose Enhancement with Gold Nanoparticles. Medical Physics, 40, Article ID: 031706.

[32]   Gao, J. and Zheng, Y. (2014) Monte Carlo Study of Secondary Electron Production from Gold Nanoparticle in Proton Beam Irradiation. International Journal of Cancer Therapy and Oncology, 2, Article ID: 02025.

[33]   Berger, M.J., Coursey, J.S., Zuker, M.A. and Chang, J. (2009) Stopping-Power and Range Tables for Electrons, Protons and Helium Ions.
http://www.nist.gov/pml/data/star/

[34]   Shmatov, ML. (2014) An Expected Increase in the Efficiency of the Antiproton and Pion Cancer Therapies at the Use of the Gold Nanopartices. Preprint of Ioffe Institute, Saint Petersburg, No. 1810.

[35]   Weil, A.G., Li, S. and Zhao, J.Z. (2011) Recurrence of a Cerebral Arteriovenous Malformation following Complete Surgical Resection: A Case Report and Review of the Literature. Surgical Neurology International, 2, 175.
http://dx.doi.org/10.4103/2152-7806.90692

[36]   Takagi, Y., Kikuta, K., Nozaki, K. and Hashimoto, N. (2010) Early Regrowth of Juvenile Cerebral Arteriovenous Malformations: Report of 3 Cases and Immunohistochemical Analysis. World Neurosurgery, 73, 100-107.
http://dx.doi.org/10.1016/j.surneu.2009.07.008

[37]   Liu, S., Sammons, V., Fairhall, J., Reddy, R., Tu, J., Hong Duong, T.T. and Stoodley, M. (2012) Molecular Response of Brain Endothelial Cells to Radiation in a Mouse Model. Journal of Clinical Neuroscience, 19, 1154-1158.
http://dx.doi.org/10.1016/j.jocn.2011.12.004

[38]   Cheng, Y., Dai, Q., Morshed, R.A., Fan, X., Wegschied, M.L., Wainwright, D.A., et al. (2014) Blood-Brain Barrier Permeable Gold Nanoparticles: An Efficient Delivery Platform for Enhanced Malignant Glioma Therapy and Imaging. Small, 10, 5137-5150.
http://dx.doi.org/10.1002/smll.201400654

[39]   Jain, S., Hirst, D.G. and O’Sullivan, J.M. (2012) Gold Nanoparticles as Novel Agents for Cancer Therapy. The British Journal of Radiology, 85, 101-113.
http://dx.doi.org/10.1259/bjr/59448833

[40]   Gale, N.W. and Yancopoulos, G.D. (1999) Growth Factors Acting via Endothelial Cell-Specific Receptor Tyrosine Kinases: VEGFs, Angiopoietins, and Ephrins in Vascular Development. Genes & Development, 13, 1055-1066.
http://dx.doi.org/10.1101/gad.13.9.1055

[41]   Fontanella, C., Ongaro, E., Bolzonello, S., Guardascione, M., Fasola, G. and Aprile, G. (2014) Clinical Advances in the Development of Novel VEGFR2 Inhibitors. Annals of Translational Medicine, 2, 123.

[42]   Smyth, E.C., Tarazona, N. and Chau, I. (2014) Ramucirumab: Targeting Angiogenesis in the Treatment of Gastric Cancer. Immunotherapy, 6, 1177-1186.
http://dx.doi.org/10.2217/imt.14.85

[43]   Zhou, D., Zhan, S., Zhou, D., Li, Z., Lin, X., Tang, K., et al. (2011) A Study of the Distribution and Density of the VEGFR-2 Receptor on Glioma Microvascular Endothelial Cell Membranes. Cellular and Molecular Neurobiology, 31, 687-694.
http://dx.doi.org/10.1007/s10571-011-9665-6

[44]   Jabbour, M.N., Elder, J.B., Samuelson, C.G., Khashabi, S., Hofman, F.M., Giannotta, S.L., et al. (2009) Aberrant Angiogenic Charactheristics of Human Brain Arteriovenous Malformation Endothelial Cells. Neurosurgery, 64, 139-146.
http://dx.doi.org/10.1227/01.NEU.0000334417.56742.24

[45]   Uranishi, R., Baev, N.I., Ng, P.Y., Kim, J.H. and Awad, I.A. (2001) Expression of Endothelial Cell Angiogenesis Receptors in Human Cerebrovascular Malformations. Neurosurgery, 48, 359-367.

[46]   Koizumi, T., Shiraishi, T., Hagihara, N., Tabuchi, K., Hayashi, T. and Kawano, T. (2002) Expression of Vascular Endothelial Growth Factors and Their Receptors in and around Intracranial Arteriovenous Malformations. Neurosurgery, 50, 117-124.

[47]   Hatva, E., Jskelinen, J., Hirvonen, H., Alitalo, K. and Haltia, M. (1996) Tie Endothelial Cell-Specific Receptor Tyrosine Kinase is Upregulated in the Vasculature of Arteriovenous Malformations. Journal of Neuropathology & Experimental Neurology, 55, 1124-1133.
http://dx.doi.org/10.1097/00005072-199611000-00003

[48]   Bai, J., Wang, Y.L., Liu, L. and Zhao, Y.L. (2014) Ephrin B2 and EphB4 Selectively Mark Arterial and Venous Vessels in Cerebral Arteriovenous Malformation. Journal of International Medical Research, 42, 405-415.
http://dx.doi.org/10.1177/0300060513478091

[49]   Corre, I., Guillonneau, M. and Paris, F. (2013) Membrane Signalling Induced by High Doses of Ionizing Radiation in the Endothelial Compartment. Relevance in Radiation Toxicity. International Journal of Molecular Sciences, 14, 22678-22696.
http://dx.doi.org/10.3390/ijms141122678

[50]   Li, J., Huang, S., Armstrong, E.A., Fowler, J.F. and Harari, P.M. (2005) Angiogenesis and Radiation Response Modulation after Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) Blockade. International Journal of Radiation Oncology, Biology, Physics, 62, 1477-1485.
http://dx.doi.org/10.1016/j.ijrobp.2005.04.028

[51]   Kim, G.H., Hahn, D.K., Kellner, C.P., Hickman, Z.L., Komotar, R.J., Starke, R.M., et al. (2008) Plasma Levels of Vascular Endothelial Growth Factor after Treatment for Cerebral Arteriovenous Malformations. Stroke, 39, 2274-2279.
http://dx.doi.org/10.1161/STROKEAHA.107.512442

[52]   Vernimmen, F.J. (2014) Vascular Endothelial Growth Factor Blockade: A Potential New Therapy in the Management of Cerebral Arteriovenous Malformations. Journal of Medical Hypotheses and Ideas, 8, 57-61.
http://dx.doi.org/10.1016/j.jmhi.2013.10.001

[53]   Ngwa, W., Makrigiorgos, G.M. and Berbeco, R.I. (2012) Gold Nanoparticle Enhancement of Stereotactic Radiosurgery for Neovascular Age-Related Macular Degeneration. Physics in Medicine and Biology, 57, 6371-6380.
http://dx.doi.org/10.1088/0031-9155/57/20/6371

[54]   Rahman, W.N., Corde, S., Yagi, N., Abdul Aziz, S.A., Annabell, N. and Geso, M. (2014) Optimal Energy for Cell Radiosenstivity Enhancement by Gold Nanoparticles Using Synchrotron-Based Monoenergetic Photon Beams. International Journal of Nanomedicine, 19, 2459-2467.
http://dx.doi.org/10.2147/IJN.S59471