Activity of psoralen-functionalized nanoscintillators against cancer cells upon X-ray excitation

ACS Nano

Volumn 5, Issue 6, 2011, Pages 4679-4687

  Scaffidi, Jonathan P ^a   Gregas, Molly K ^a   Lauly, Benoit ^a   Zhang, Yan ^a   Vo Dinh, Tuan ^a,b  

^a Duke University   (United States)

^b DUKE UNIVERSITY   (United States)

Author keywords

nanoscintillator; psoralen; PUVA; Y2O3; yttrium oxide

Indexed keywords

CANCER CELLS; CELL NUMBER; CONCENTRATION-DEPENDENT; CONTROL CULTURES; FUNCTIONALIZED; HIV-1 TAT; HUMAN PROSTATE CANCER CELLS; IN-VITRO; IN-VIVO; NANOSCINTILLATOR; PSORALEN; PUVA; UV-A LIGHT; X RAY RADIATION; X-RAY EXCITATION;

CELL CULTURE; CELL DEATH; DISEASES; LIGHT; MULTIPHOTON PROCESSES; NANOPARTICLES; POLYPEPTIDES; X RAYS; YTTRIUM; YTTRIUM OXIDE;

YTTRIUM ALLOYS;

ADENINE; DNA; PSORALEN; THYMINE; TRANSACTIVATOR PROTEIN; YTTRIA; YTTRIUM;

APOPTOSIS; ARTICLE; CHEMISTRY; DRUG SCREENING; HUMAN; MALE; METHODOLOGY; NANOTECHNOLOGY; PROSTATE TUMOR; PUVA; TUMOR CELL LINE; X RAY;

ADENINE; APOPTOSIS; CELL LINE, TUMOR; DNA; DRUG SCREENING ASSAYS, ANTITUMOR; FICUSIN; HUMANS; MALE; NANOTECHNOLOGY; PROSTATIC NEOPLASMS; PUVA THERAPY; TAT GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS; THYMINE; X-RAYS; YTTRIUM;

EID: 79959791084     PISSN: 19360851     EISSN: 1936086X     Source Type: Journal    
DOI: 10.1021/nn200511m     Document Type: Article

References (92)

1. Brigger, I.; Dubernet, C.; Couvreur, P. Nanoparticles in Cancer Therapy and Diagnosis Adv. Drug Delivery Rev. 2002, 54, 631-651 (Pubitemid 35247520)
2. Yih, T. C.; Wei, C. Nanomedicine in Cancer Treatment Nanomedicine (N. Y., NY, U. S.) 2005, 1, 191-192 (Pubitemid 43963618)
3. Cuenca, A. G.; Jiang, H. B.; Hochwald, S. N.; Delano, M.; Cance, W. G.; Grobmyer, S. R. Emerging Implications of Nanotechnology on Cancer Diagnostics and Therapeutics Cancer 2006, 107, 459-466 (Pubitemid 44107204)
4. Huang, X.; Jain, P. K.; El-Sayed, I. H.; El-Sayed, M. A. Gold Nanoparticles: Interesting Optical Properties and Recent Applications in Cancer Diagnostics and Therapy Nanomedicine (N. Y., NY, U. S.) 2007, 2, 681-693 (Pubitemid 350268247)
5. Gulyaev, A. E.; Gelperina, S. E.; Skidan, I. N.; Antropov, A. S.; Kivman, G. Y.; Kreuter, J. Significant Transport of Doxorubicin into the Brain with Polysorbate 80-Coated Nanoparticles Pharm. Res. 1999, 16, 1564-1569 (Pubitemid 29510553)
6. Song, M.; Wang, X. M.; Li, J. Y.; Zhang, R. Y.; Chen, B. A.; Fu, D. G. Effect of Surface Chemistry Modification of Functional Gold Nanoparticles on the Drug Accumulation of Cancer Cells J. Biomed. Mater. Res., Part A 2008, 86A, 942-946
7. Nystrom, A. M.; Xu, Z. Q.; Xu, J. Q.; Taylor, S.; Nittis, T.; Stewart, S. A.; Leonard, J.; Wooley, K. L. SCKs as Nanoparticle Carriers of Doxorubicin: Investigation of Core Composition on the Loading, Release and Cytotoxicity Profiles Chem. Commun. 2008, 3579-3581
8. Rapoport, N.; Gao, Z. G.; Kennedy, A. Multifunctional Nanoparticles for Combining Ultrasonic Tumor Imaging and Targeted Chemotherapy J. Natl. Cancer Inst. 2007, 99, 1095-1106 (Pubitemid 47241394)
9. Zhang, Z.; Lee, S.; Gan, C.; Feng, S.-S. Investigation on PLA-TPGS Nanoparticles for Controlled and Sustained Small Molecule Chemotherapy Pharm. Res. 2008, 25, 1925-1935
10. Dong, Y.; Feng, S. S. Poly(D,L-Lactide-Co-Glycolide) (PLGA) Nanoparticles Prepared by High Pressure Homogenization for Paclitaxel Chemotherapy Int. J. Pharm. 2007, 342, 208-214 (Pubitemid 47263496)
11. Li, J.; Wang, X.; Wang, C.; Chen, B.; Dai, Y.; Zhang, R.; Song, M.; Lv, G.; Fu, D. The Enhancement Effect of Gold Nanoparticles in Drug Delivery and as Biomarkers of Drug-Resistant Cancer Cells ChemMedChem 2007, 2, 374-378
12. Roeske, J. C.; Nunez, L.; Hoggarth, M.; Labay, E.; Weichselbaum, R. R. Characterization of the Theorectical Radiation Dose Enhancement from Nanoparticles Technol. Cancer Res. Treat. 2007, 6, 395-401 (Pubitemid 47613287)
13. ONeal, D. P.; Hirsch, L. R.; Halas, N. J.; Payne, J. D.; West, J. L. Photo-Thermal Tumor Ablation in Mice Using near Infrared-Absorbing Nanoparticles Cancer Lett. 2004, 209, 171-176 (Pubitemid 38670486)
14. El-Sayed, I. H.; Huang, X.; El-Sayed, M. A. Selective Laser Photo-Thermal Therapy of Epithelial Carcinoma Using Anti-EGFR Antibody Conjugated Gold Nanoparticles Cancer Lett. 2006, 239, 129-135 (Pubitemid 43946581)
15. Zhang, R. Y.; Wang, X. M.; Wu, C. H.; Song, M.; Li, J. Y.; Lv, G.; Zhou, J.; Chen, C.; Dai, Y. Y.; Gao, F. et al. Synergistic Enhancement Effect of Magnetic Nanoparticles on Anticancer Drug Accumulation in Cancer Cells Nanotechnology 2006, 17, 3622-3626 (Pubitemid 43996758)
16. Visaria, R. K.; Griffin, R. J.; Williams, B. W.; Ebbini, E. S.; Paciotti, G. F.; Song, C. W.; Bischof, J. C. Enhancement of Tumor Thermal Therapy Using Gold Nanoparticle-Assisted Tumor Necrosis Factor-Alpha Delivery Mol. Cancer Ther. 2006, 5, 1014-1020 (Pubitemid 43724602)
17. Liu, C. J.; Wang, C. H.; Chien, C. C.; Yang, T. Y.; Chen, S. T.; Leng, W. H.; Lee, C. F.; Lee, K. H.; Hwu, Y.; Lee, Y. C. et al. Enhanced X-Ray Irradiation-Induced Cancer Cell Damage by Gold Nanoparticles Treated by a New Synthesis Method of Polyethylene Glycol Modification Nanotechnology 2008, 19, 295104
18. Kong, T.; Zeng, J.; Wang, X. P.; Yang, X. Y.; Yang, J.; McQuarrie, S.; McEwan, A.; Roa, W.; Chen, J.; Xing, J. Z. Enhancement of Radiation Cytotoxicity in Breast-Cancer Cells by Localized Attachment of Gold Nanoparticles Small 2008, 4, 1537-1543
19. Wang, S. Z.; Gao, R. M.; Zhou, F. M.; Selke, M. Nanomaterials and Singlet Oxygen Photosensitizers: Potential Applications in Photodynamic Therapy J. Mater. Chem. 2004, 14, 487-493
20. Takahashi, J.; Misawa, M. Analysis of Potential Radiosensitizing Materials for X-Ray-Induced Photodynamic Therapy NanoBiotechnology 2007, 3, 116-126
21. Morgan, N. Y.; Kramer-Marek, G.; Smith, P. D.; Camphausen, K.; Capala, J. Nanoscintillator Conjugates as Photodynamic Therapy-Based Radiosensitizers: Calculation of Required Physical Parameters Radiat. Res. 2009, 171, 236-244
22. Chatterjee, D. K.; Fong, L. S.; Zhang, Y. Nanoparticles in Photodynamic Therapy: An Emerging Paradigm Adv. Drug Delivery Rev. 2008, 60, 1627-1637
23. Liu, Y. F.; Chen, W.; Wang, S. P.; Joly, A. G. Investigation of Water-Soluble X-Ray Luminescence Nanoparticles for Photodynamic Activation Appl. Phys. Lett. 2008, 92, 043901
24. Chen, W.; Zhang, J. Using Nanoparticles to Enable Simultaneous Radiation and Photodynamic Therapies for Cancer Treatment J. Nanosci. Nanotechnol. 2006, 6, 1159-1166 (Pubitemid 44578047)
25. Juzenas, P.; Chen, W.; Sun, Y. P.; Coelho, M. A. N.; Generalov, R.; Generalova, N.; Christensen, I. L. Quantum Dots and Nanoparticles for Photodynamic and Radiation Therapies of Cancer Adv. Drug Delivery Rev. 2008, 60, 1600-1614
26. Lovell, J. F.; Liu, T. W. B.; Chen, J.; Zheng, G. Activatable Photosensitizers for Imaging and Therapy Chem. Rev. 2010, 110, 2839-2857
27. Wang, L.; Yang, W. S.; Read, P.; Larner, J.; Sheng, K. Tumor Cell Apoptosis Induced by Nanoparticle Conjugate in Combination with Radiation Therapy Nanotechnology 2010, 21, 475103
28. Quintiliani, M. Modification of Radiation Sensitivity: The Oxygen Effect Int. J. Radiat. Oncol. Biol. Phys. 1979, 5, 1069-1076 (Pubitemid 10191567)
29. Henderson, B. W.; Fingar, V. H. Relationship of Tumor Hypoxia and Response to Photodynamic Therapy Treatment in an Experimental Mouse-Tumor Cancer Res. 1987, 47, 3110-3114 (Pubitemid 17082632)
30. Chaplin, D. J.; Durand, R. E.; Olive, P. L. Acute Hypoxia in Tumors: Implications for Modifiers of Radiation Effects Int. J. Radiat. Oncol. Biol. Phys. 1986, 12, 1279-1282 (Pubitemid 16030598)
31. Huang, Z.; Chen, Q.; Shakil, A.; Chen, H.; Beckers, J.; Shapiro, H.; Hetzel, F. W. Hyperoxygenation Enhances the Tumor Cell Killing of Photofrin-Mediated Photodynamic Therapy Photochem. Photobiol. 2003, 78, 496-502
32. Gasparro, F. P.; Felli, A.; Schmitt, I. M. Psoralen Photobiology: The Relationship between DNA Damage, Chromatin Structure, Transcription, and Immunogenic Effects Recent Results Cancer Res. 1997, 143, 101-127
33. Malane, M. S.; Gasparro, F. P. T Cell Molecular Targets for Psoralens Ann. N.Y. Acad. Sci. 1991, 636, 196-208
34. Bethea, D.; Fullmer, B.; Syed, S.; Seltzer, G.; Tiano, J.; Rischko, C.; Gillespie, L.; Brown, D.; Gasparro, F. P. Psoralen Photobiology and Photochemotherapy: 50 Years of Science and Medicine J. Dermatol. Sci. 1999, 19, 78-88 (Pubitemid 29096438)
35. Shah, K. S.; Glodo, J.; Higgins, W.; Loef, E. V. D. v.; Moses, W. W.; Derenzo, S. E.; Weber, M. J. CeBr3 Scintillators for Gamma-Ray Spectroscopy IEEE Trans. Nucl. Sci. 2005, 52, 3157-3159
36. 3+ Crystals: Fast, Efficient, and High-Energy Resolution Scintillators IEEE Trans. Nucl. Sci. 2001, 48, 341-345 (Pubitemid 32949811)
37. 3:Ce Crystals Radiat. Eff. Defects Solids 1995, 135, 819-821
38. Roy, U. N.; Groza, M.; Cui, Y.; Burger, A.; Cherepy, N.; Friedrich, S.; Payne, S. A. A New Scintillator Material Nucl. Instrum. Methods Phys. Res., Sect. A 2007, 579, 46-49
39. 3+ (X = Cl, Br, I) Nucl. Instrum. Methods Phys. Res., Sect. A 2005, 537, 232-236
40. 5 J. Lumin. 1999, 85, 1-10 (Pubitemid 129590895)
41. 5 with Ce Doping Radiat. Meas. 1995, 24, 379-381
42. 3+-Doped AREP2O7-Type Alkali Rare Earth Diphospates (a = Na, K, Pb, Cs; Re = Y, Lu) J. Solid State Chem. 2007, 180, 3381-3387 (Pubitemid 350212928)
43. 3+ Crystals: Fast, Efficient and High-Energy-Resolution Scintillators Nucl. Instrum. Methods Phys. Res., Sect. A 2002, 486, 254-258 (Pubitemid 34661579)
44. Menge, P. R.; Gautier, G.; Iltis, A.; Rozsa, C.; Solovyev, V. Performance of Large Lanthanum Bromide Scintillators Nucl. Instrum. Methods Phys. Res., Sect. A 2007, 579, 6-10 (Pubitemid 47211352)
45. Haas, J. T. M. d.; Dorenbos, P. Advances in Yield Calibration of Scintillators IEEE Trans. Nucl. Sci. 2008, 55, 1086-1092
46. Salacka, J. S.; Bacrania, M. K. A Comprehensive Technique for Determining the Intrinsic Light Yield of Scintillators IEEE Trans. Nucl. Sci. 2010, 57, 901-909
47. Moszynski, M.; Wolski, D.; Ludziejewski, T.; Kapusta, M.; Lempicki, A.; Brecher, C.; Wisniewski, D.; Wojtowicz, A. J. Properties of the New LuAP:Ce Scintillator Nucl. Instrum. Methods Phys. Res., Sect. A 1997, 385, 123-131 (Pubitemid 127376051)
48. 3-Ce-a High-Density, High-Speed Scintillator for Gamma-Detection IEEE Trans. Nucl. Sci. 1995, 42, 275-279
49. Moszynski, M.; Kapusta, M.; Mayhugh, M.; Wolski, D.; Flyckt, S. O. Absolute Light Output of Scintillators IEEE Trans. Nucl. Sci. 1997, 44, 1052-1061 (Pubitemid 127764953)
50. 3-Ce and Other Aluminate Scintillators IEEE Trans. Nucl. Sci. 1995, 42, 280-284
51. Lempicki, A.; Berman, E.; Wojtowicz, A. J.; Balcerzyk, M.; Boatner, L. A. Cerium-Doped Orthophosphates-New Promising Scintillators IEEE Trans. Nucl. Sci. 1993, 40, 384-387
52. Moses, W. W.; Derenzo, S. E.; Shlichta, P. J. Scintillation Properties of Lead Sulfate IEEE Trans. Nucl. Sci. 1992, 39, 1190-1194 (Pubitemid 23608588)
53. 4 Crystals Inorg. Mater. 2004, 40, 735-739
54. Zhang, J. G.; Lund, J. C.; Cirignano, L.; Shah, K. S.; Squillante, M. R.; Moses, W. W. Lead Sulfate Scintillator Crystal Growth for PET Applications IEEE Trans. Nucl. Sci. 1994, 41, 669-674
55. 3+: A New Fast Lanthanide Trihalide Scintillator IEEE Trans. Nucl. Sci. 2006, 53, 3028-3030 (Pubitemid 44637062)
56. Ogorodnikov, I. N.; Kruzhalov, A. V.; Ivanov, V. Y. Mechanisms of Fast UV-Scintillations in Oxide Crystals with Self-Trapped Excitons. In Inorganic Scintillators and Their Applications; Delft University Press (SCINT95): Amsterdam, The Netherlands, 1996; pp 216-219.
57. Baryshevsky, V. G.; Korzhik, M. V.; Moroz, V. I.; Pavlenko, V. B.; Fyodorov, A. A.; Smirnova, S. A.; Egorycheva, O. A.; Kachanov, V. A. YAlO3-Ce-Fast-Acting Scintillators for Detection of Ionizing-Radiation Nucl. Instrum. Methods Phys. Res., Sect. B 1991, 58, 291-293
58. Mares, J. A.; Beitlerova, A.; Nikl, M.; Solovieva, N.; DAmbrosio, C.; Blazek, K.; Maly, P.; Nejezchleb, K.; Notaristefani, F. d. Scintillation Response of Ce-Doped or Intrinsic Scintillating Crystals in the Range up to 1 MeV Radiat. Meas. 2004, 38, 353-357
59. de Haas, J. T. M.; Dorenbos, P.; van Eijk, C. W. E. Measuring the Absolute Light Yield of Scintillators Nucl. Instrum. Methods Phys. Res., Sect. A 2005, 537, 97-100 (Pubitemid 40072422)
60. Zako, T.; Nagata, H.; Terada, N.; Sakono, M.; Soga, K.; Maeda, M. Improvement of Dispersion Stability and Characterization of Upconversion Nanophosphors Covalently Modified with PEG as a Fluorescence Bioimaging Probe J. Mater. Sci. 2008, 43, 5325-5330
61. 3 Nanocrystals Nanotechnology 2004, 15, 75-81
62. 2+ Nanocomposite Phosphors J. Appl. Phys. 2006, 99, 034302
63. 3+ Water-Soluble Nanoparticles J. Appl. Phys. 2008, 103, 063105-063105-7
64. 3+ Nanoparticles Mater. Sci. Eng. B 2006, 130, 151-157
65. 3:Ce J. Lumin. 1997, 72-74, 789-791
66. 3:Ce J. Phys.: Condens. Matter 2001, 13, 9599-9619 (Pubitemid 33036726)
67. 3+ Doped Halide Scintillators Phys. Status Solidi A 2005, 202, 195-200 (Pubitemid 41365177)
68. Gregas, M. K.; Scaffidi, J. P.; Lauly, B.; Vo-Dinh, T. Surface-Enhanced Raman Scattering Detection and Tracking of Nanoprobes: Enhanced Uptake and Nuclear Targeting in Single Cells Appl. Spectrosc. 2010, 64, 858-866
69. Fawell, S.; Seery, J.; Daikh, Y.; Moore, C.; Chen, L. L.; Pepinsky, B.; Barsoum, J. Tat-Mediated Delivery of Heterologous Proteins into Cells Proc. Natl. Acad. Sci. U. S. A. 1994, 91, 664-8 (Pubitemid 24041462)
70. Brooks, H.; Lebleu, B.; Vives, E. Tat Peptide-Mediated Cellular Delivery: Back to Basics Adv. Drug Delivery Rev. 2005, 57, 559-577 (Pubitemid 40255561)
71. Zorko, M.; Langel, U. Cell-Penetrating Peptides: Mechanism and Kinetics of Cargo Delivery Adv. Drug Delivery Rev. 2005, 57, 529-545 (Pubitemid 40255559)
72. Reis, P. A.; Valente, L. M. P.; Almeida, C. M. R. A Fast and Simple Methodology for Determination of Yttrium as an Inert Marker in Digestibility Studies Food Chem. 2008, 108, 1094-1098
73. Schubert, D.; Dargusch, R.; Raitano, J.; Chan, S. W. Cerium and Yttrium Oxide Nanoparticles Are Neuroprotective Biochem. Biophys. Res. Commun. 2006, 342, 86-91 (Pubitemid 43247363)
74. Torchilin, V. P.; Levchenko, T. S.; Rammohan, R.; Volodina, N.; Papahadjopoulos-Sternberg, B.; DSouza, G. G. M. Cell Transfection in Vitro and in Vivo with Nontoxic Tat Peptide-Liposome-DNA Complexes Proc. Natl. Acad. Sci. U. S. A. 2003, 100, 1972-1977 (Pubitemid 36254558)
75. Manickam, D. S.; Bisht, H. S.; Wan, L.; Mao, G. Z.; Oupicky, D. Influence of Tat-Peptide Polymerization on Properties and Transfection Activity of Tat/DNA Polyplexes J. Controlled Release 2005, 102, 293-306 (Pubitemid 40093793)
76. Kim, K.; Han, J.; Kim, H.; Lee, M. Expression, Purification and Characterization of Tat-High Mobility Group Box-1a Peptide as a Carrier of Nucleic Acids Biotechnol. Lett. 2008, 30, 1331-1337
77. Weisenthal, L. M.; Dill, P. L.; Kurnick, N. B.; Lippman, M. E. Comparison of Dye Exclusion Assays with a Clonogenic-Assay in the Determination of Drug-Induced Cyto-Toxicity Cancer Res. 1983, 43, 258-264 (Pubitemid 13172827)
78. Plumb, J. A. Ch. 2-Cell Sensitivity Assays/Clonogenic Assay. In Cytotoxic Drug Resistance Mechanisms; Brown, R.; Boger-Brown, U., Eds.; Humana Press: Totowa, NJ, 1999; pp 25-30.
79. Franken, N. A. P.; Rodermond, H. M.; Stap, J.; Haveman, J.; van Bree, C. Clonogenic Assay of Cells in Vitro Nat. Protoc. 2006, 1, 2315-2319
80. Mueller, H.; Kassack, M. U.; Wiese, M. Comparison of the Usefulness of the MTT, ATP, and Calcein Assays to Predict the Potency of Cytotoxic Agents in Various Human Cancer Cell Lines J. Biomol. Screen. 2004, 9, 506-515
81. Gorodetsky, R.; Mou, X.; Pfeffer, M. R.; Peretz, T.; Levy-Agababa, F.; Vexler, A. M. Sub-Additive Effect of the Combination of Radiation and Cisplatin in Cultured Murine and Human Cell Lines Isr. J. Med. Sci. 1995, 31, 95-100
82. Felice, D. L.; Sun, J.; Liu, R. H. A Modified Methylene Blue Assay for Accurate Cell Counting J. Funct. Foods 2009, 1, 109-118
83. Oliver, M. H.; Harrison, N. K.; Bishop, J. E.; Cole, P. J.; Laurent, G. J. A Rapid and Convenient Assay for Counting Cells Cultured in Microwell Plates Application for Assessment of Growth Factors J. Cell Sci. 1989, 92, 513-518 (Pubitemid 19083806)
84. Pelletier, B.; Dhainaut, F.; Pauly, A.; Zahnd, J. P. Evaluation of Growth Rate in Adhering Cell Cultures Using a Simple Colorimetric Method J. Biochem. Biophys. Methods 1988, 16, 63-73
85. Dent, M. F.; Hubbold, L.; Radford, H.; Wilson, A. P. The Methylene Blue Colorimetric Microassay for Determining Cell Line Response to Growth Factors Cytotechnology 1995, 17, 27-33
86. Scragg, M. A.; Ferreira, L. R. Evaluation of Different Staining Procedures for the Quantification of Fibroblasts Cultured in 96-Well Plates Anal. Biochem. 1991, 198, 80-85
87. Chithrani, D. B.; Jelveh, S.; Jalali, F.; van Prooijen, M.; Allen, C.; Bristow, R. G.; Hill, R. P.; Jaffray, D. A. Gold Nanoparticles as Radiation Sensitizers in Cancer Therapy Radiat. Res. 2010, 173, 719-728
88. Chiu, S. J.; Lee, M. Y.; Chou, W. G.; Lin, L. Y. Germanium Oxide Enhances the Radiosensitivity of Cells Radiat. Res. 2003, 159, 391-400
89. Hainfeld, J. F.; Slatkin, D. N.; Smilowitz, H. M. The Use of Gold Nanoparticles to Enhance Radiotherapy in Mice Phys. Med. Biol. 2004, 49, N309-N315
90. Hainfeld, J. F.; Dilmanian, F. A.; Zhong, Z.; Slatkin, D. N.; Kalef-Ezra, J. A.; Smilowitz, H. M. Gold Nanoparticles Enhance the Radiation Therapy of a Murine Squamous Cell Carcinoma Phys. Med. Biol. 2010, 55, 3045-3059
91. Kim, J. K.; Seo, S. J.; Kim, K. H.; Kim, T. J.; Chung, M. H.; Kim, K. R.; Yang, T. K. Therapeutic Application of Metallic Nanoparticles Combined with Particle-Induced X-Ray Emission Effect Nanotechnology 2010, 21, 425102
92. Chattopadhyay, N.; Cai, Z. L.; Pignol, J. P.; Keller, B.; Lechtman, E.; Bendayan, R.; Reilly, R. M. Design and Characterization of HER-2-Targeted Gold Nanoparticles for Enhanced X-Radiation Treatment of Locally Advanced Breast Cancer Mol. Pharmaceutics 2010, 7, 2194-2206