研究生: |
陳玠瑋 Chen, Chieh-Wei |
---|---|
論文名稱: |
金奈米棒於酸鹼及光熱應答型藥物載體設計及其於癌症標靶治療之應用 pH-Responsive Drug Release from Gold Nanorods by NIR irradiation for Targeted Drug Delivery |
指導教授: |
黃郁棻
Huang, Yu-Fen |
口試委員: |
黃志清
張建文 王福年 |
學位類別: |
碩士 Master |
系所名稱: |
原子科學院 - 生醫工程與環境科學系 Department of Biomedical Engineering and Environmental Sciences |
論文出版年: | 2012 |
畢業學年度: | 100 |
語文別: | 中文 |
論文頁數: | 99 |
中文關鍵詞: | 金奈米棒 、藥物傳遞 、光熱轉換效應 |
外文關鍵詞: | Gold nanorod, Drug delivery, Photothermal effect |
相關次數: | 點閱:3 下載:0 |
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激活性奈米材料泛指材料在受到外力刺激時,會產生物理或化學現象的改變,例如產生熱、光、化學反應、和體積及運動模式改變等,近年來在生醫領域備受矚目。本研究利用連續波型的808 nm雷射照射金奈米棒 (Au NRs),使Au NRs吸收雷射能量轉換而成的熱能,能加速其表面具有酸鹼應答特性之藥物–PDPH-Dox釋放行為,提高藥物治療果效。為減少藥物在傳遞過程因生理酸鹼值(pH 7.4)導致藥物滲漏產生之毒性,Dox以共價性鍵結修飾於Au NRs上。然而在酸性環境下(pH 4.5~5.5)藥物Dox和載體(Au NRs)之間的腙鍵結 (Hydrazone bond)會被酸解而從載體上釋放出藥物。為增進載體對於目標細胞(CCRF-CEM)的特異性標定,同時在Au NRs表面組裝眾多對於有強親和力的適體–Sgc8c。此外,因巨噬細胞可於腫瘤區域累積,為增進奈米藥物對於腫瘤的傳遞效率,將Sgc8c替換為玻尿酸的奈米藥物載體,可與巨噬細胞(RAW 264.7)表面的CD44藉由特異性標定累積於細胞內,形成一細胞型載體。研究結果顯示,本研究成功開發一兼具酸鹼值和近紅外光應答特性之新型奈米藥物載體,透過雷射光照射,可精準控制奈米載體在細胞內的釋藥行為,藉此雙重釋藥機制可結合藥物及光熱治療,提升毒殺癌細胞效率。同時利用細胞型載體以共培養方式,照射NIR雷射毒殺另一癌細胞Tramp-C1。
In this study, a doxorubicin (Dox) conjugated gold nanorod (Dox-Au NR) which exhibits a pH-responsive drug release profile has been constructed successfully. The antitumor drug Dox was covalently linked to Au NRs to reduce the overall toxicity of the drug in physiological conditions. However, the acid-labile hydrazone linker, connecting the Dox-Au NR conjugates could be cleaved in an acidic environment. Furthermore, multiple aptamers, sgc8c have also been assembled on the NR surface, providing strong binding affinity with targeted cancer cells through simultaneous multivalent interactions with the cell membrane receptors. Owing to the photothermal effect that Au NR could convert the absorbed light energy to heat, CCRF-CEM cells incubated with Dox-Au NR conjugates were greatly damaged after near-infrared (NIR) light exposure. Our results demonstrated that these novel drug nanocarriers which combine pH- and NIR-responsiveness are highly promising for precise drug releasing in targeted drug delivery. Furthermore, an efficient approach for tumor-targeted drug delivery system was developed with macorphage (RAW 264.7) as the targeting vehicle and a hyaluronic acid conjugated gold nanorod (HA-Au NR) as the drug carrier. This novel strategy provides a great potential to actively deliver nano-therapeutics to tumors utilizing macrophages as tumor-tropic carriers. The synergistic NIR photothermally enhanced drug release of HA/Dox-Au NRs also provides a considerable contribution to enhanced tumor-cell(Tramp-C1) apoptosis and low systematic toxicity.
4 參考文獻
1. Anisa, M.; Abdallah, S. D.; Peter, A. S., 'Mind the gap': science and ethics in nanotechnology. Nanotechnology 2003, 14, R9-R13.
2. Forbes, P., Self-Cleaning Materials. Sci. Am. 2008, 299, 88-95.
3. Lafuma, A.; Quere, D., Superhydrophobic states. Nat. Mater. 2003, 2, 457-460.
4. Kubo, R., Electronic Properties of Metallic Fine Particles. I. J. Phys. Soc. Jpn. 1962, 17, 975-986.
5. Ekimov, A. I.; Efros, A. L.; Onushchenko, A. A., Quantum size effect in semiconductor microcrystals. Solid State Commun. 1985, 56, 921-924.
6. El-Sayed, M. A., Some Interesting Properties of Metals Confined in Time and Nanometer Space of Different Shapes. Acc. Chem. Res. 2001, 34, 257-264.
7. Mizukoshi, Y.; Makise, Y.; Shuto, T.; Hu, J.; Tominaga, A.; Shironita, S.; Tanabe, S., Immobilization of noble metal nanoparticles on the surface of TiO2 by the sonochemical method: Photocatalytic production of hydrogen from an aqueous solution of ethanol. Ultrason. Sonochem. 2007, 14, 387-392.
8. Grimme, R. A.; Lubner, C. E.; Bryant, D. A.; Golbeck, J. H., Photosystem I/Molecular Wire/Metal Nanoparticle Bioconjugates for the Photocatalytic Production of H2. J. Am. Chem. Soc. 2008, 130, 6308-6309.
9. Wood, R. W., On a Remarkable Case of Uneven Distribution of Light in a Diffraction Grating Spectrum. Proc. Phys. Soc. London 1902, 18, 269-275.
10. Fano, U., The Theory of Anomalous Diffraction Gratings and of Quasi-Stationary Waves on Metallic Surfaces (Sommerfeld?s Waves). J. Opt. Soc. Am. 1941, 31, 213-222.
11. Homola, J.; Yee, S. S.; Gauglitz, G., Surface plasmon resonance sensors: review. Sens. Actuators, B 1999, 54, 3-15.
12. H. Raether, Surface Plasmons Springer, New York; 1988.
13. Zayats, A. V.; Smolyaninov, I. I.; Maradudin, A. A., Nano-optics of surface plasmon polaritons. Phys. Rep. 2005, 408, 131-314.
14. Markey, F. What is SPR anyway? BIA J. 1999, 6, 14-17.
15. Pattnaik, P., Surface plasmon resonance. Appl. Biochem. Biotechnol. 2005, 126, 79-92.
16. Otto, A., Excitation of nonradiative surface plasma waves in silver by the method of frustrated total reflection. Z. Phys. A: Hadrons Nucl. 1968, 216, 398-410.
17. Kretschmann, E.; Raether, H., Radiative decay of non-radiative surface plasmons excited by light, Z. Naturforsch., A: Phys. Sci. 1968, 23, 2135-2136.
18. Nylander, C.; Liedberg, B.; Lind, T., Gas detection by means of surface plasmon resonance. Sens. Actuators 1982, 3, 79-88.
19. Liedberg, B.; Nylander, C.; Lunström, I., Surface plasmon resonance for gas detection and biosensing. Sens. Actuators 1983, 4, 299-304.
20. Liedberg, B.; Nylander, C.; Lundström, I., Biosensing with surface plasmon resonance — how it all started. Biosens. Bioelectron. 1995, 10, i-ix.
21. Malmqvist, M., Biospecific interaction analysis using biosensor technology. Nature 1993, 361, 186-187.
22. Cooper, M. A., Optical biosensors in drug discovery. Nat. Rev. Drug Discovery 2002, 1, 515-528.
23. Takeda, H.; Fukumoto, A.; Miura, A.; Goshima, N.; Nomura, N., High-throughput kinase assay based on surface plasmon resonance suitable for native protein substrates. Anal. Biochem. 2006, 357, 262-271.
24. Faraday, M., The Bakerian Lecture: Experimental Relations of Gold (and Other Metals) to Light. Philos. Trans. R. Soc. London 1857, 147, 145-181.
25. Eustis, S.; El-Sayed, M. A., Why gold nanoparticles are more precious than pretty gold: Noble metal surface plasmon resonance and its enhancement of the radiative and nonradiative properties of nanocrystals of different shapes. Chem. Soc. Rev. 2006, 35, 209-217.
26. Freestone, I.; Meeks, N.; Sax, M.; Higgitt, C., The Lycurgus Cup-A Roman nanotechnology. Gold Bulletin 2007, 40, 270-277.
27. Mie, G., Beiträge zur Optik trüber Medien, speziell kolloidaler Metallösungen. Ann. Phys. 1908, 330, 377-445.
28. Bohren CF, Huffman DR (Eds). Absorption and Scattering of Light by Small Particles. Wiley, NY, USA; 1983.
29. Kelly, K. L.; Coronado, E.; Zhao, L. L.; Schatz, G. C., The Optical Properties of Metal Nanoparticles: The Influence of Size, Shape, and Dielectric Environment. J. Phys. Chem. B 2002, 107, 668-677.
30. Willets, K. A.; Van Duyne, R. P., Localized Surface Plasmon Resonance Spectroscopy and Sensing. Annu. Rev. Phys. Chem. 2007, 58, 267-297.
31. Langer, R., New methods of drug delivery. Science 1990, 249, 1527-1533.
32. Allen, T. M.; Cullis, P. R., Drug Delivery Systems: Entering the Mainstream. Science 2004, 303, 1818-1822.
33. Adair, J. H.; Parette, M. P.; Altınoğlu, E. I.; Kester, M., Nanoparticulate Alternatives for Drug Delivery. ACS Nano 2010, 4, 4967-4970.
34. Wagner, V.; Dullaart, A.; Bock, A.-K.; Zweck, A., The emerging nanomedicine landscape. Nat. Biotechnol. 2006, 24, 1211-1217.
35. Bangham, A. D.; Horne, R. W., Negative staining of phospholipids and their structural modification by surface-active agents as observed in the electron microscope. J. Mol. Biol. 1964, 8, 660-668.
36. Bangham, A. D.; Standish, M. M.; Watkins, J. C., Diffusion of univalent ions across the lamellae of swollen phospholipids. J. Mol. Biol. 1965, 13, 238-252.
37. Yatvin, M.; Kreutz, W.; Horwitz, B.; Shinitzky, M., pH-sensitive liposomes: possible clinical implications. Science 1980, 210, 1253-1255.
38. Leserman, L. D.; Barbet, J.; Kourilsky, F.; Weinstein, J. N. Targeting to cells of fluorescent liposomes covalently coupled with monoclonal antibody or protein A. Nature 1980, 288, 602-604.
39. Heath, T.; Fraley, R.; Papahdjopoulos, D., Antibody targeting of liposomes: cell specificity obtained by conjugation of F(ab')2 to vesicle surface. Science 1980, 210, 539-541.
40. Allen, T. M.; Chonn, A., Large unilamellar liposomes with low uptake into the reticuloendothelial system. FEBS Lett. 1987, 223, 42-46.
41. Klibanov, A. L.; Maruyama, K.; Torchilin, V. P.; Huang, L., Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett. 1990, 268, 235-237.
42. Gref, R.; Minamitake, Y.; Peracchia, M.; Trubetskoy, V.; Torchilin, V.; Langer, R., Biodegradable long-circulating polymeric nanospheres. Science 1994, 263, 1600-1603.
43. Farokhzad, O. C.; Langer, R., Impact of Nanotechnology on Drug Delivery. ACS Nano 2009, 3, 16-20.
44. Shi, J.; Votruba, A. R.; Farokhzad, O. C.; Langer, R., Nanotechnology in Drug Delivery and Tissue Engineering: From Discovery to Applications. Nano Lett. 2010, 10, 3223-3230.
45. Adiseshaiah, P. P.; Hall, J. B.; McNeil, S. E., Nanomaterial standards for efficacy and toxicity assessment. Wiley Interdisciplinary review 2010, 2, 99-112.
46. Moghimi, S. M.; Hunter, A. C.; Murray, J. C., Long-Circulating and Target-Specific Nanoparticles: Theory to Practice. Pharmacol. Rev. 2001, 53, 283-318.
47. Moghimi, S. M.; Szebeni, J., Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties. Prog. Lipid Res. 2003, 42, 463-478.
48. Noguchi, Y.; Wu, J.; Duncan, R.; Strohalm, J.; Ulbrich, K.; Akaike, T.; Maeda, H., Early Phase Tumor Accumulation of Macromolecules: A Great Difference in Clearance Rate between Tumor and Normal Tissues. Cancer Sci. 1998, 89, 307-314.
49. Hobbs, S. K.; Monsky, W. L.; Yuan, F.; Roberts, W. G.; Griffith, L.; Torchilin, V. P.; Jain, R. K., Regulation of transport pathways in tumor vessels: Role of tumor type and microenvironment. Proc. Natl. Acad. Sci. U. S. A. 1998, 95, 4607-4612.
50. Hashizume, H.; Baluk, P.; Morikawa, S.; McLean, J. W.; Thurston, G.; Roberge, S.; Jain, R. K.; McDonald, D. M., Openings between Defective Endothelial Cells Explain Tumor Vessel Leakiness. Am. J. Physiol. 2000, 156, 1363-1380.
51. Davis, M. E.; Chen, Z.; Shin, D. M., Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat. Rev. Drug Discovery 2008, 7, 771-782.
52. Kelkar, S. S.; Reineke, T. M., Theranostics: Combining Imaging and Therapy. Bioconjugate Chem. 2011, 22, 1879-1903.
53. Bardhan, R.; Lal, S.; Joshi, A.; Halas, N. J., Theranostic Nanoshells: From Probe Design to Imaging and Treatment of Cancer. Acc. Chem. Res. 2011, 44, 936-946.
54. Brinson, B. E.; Lassiter, J. B.; Levin, C. S.; Bardhan, R.; Mirin, N.; Halas, N. J., Nanoshells Made Easy: Improving Au Layer Growth on Nanoparticle Surfaces. Langmuir 2008, 24, 14166-14171.
55. Lal, S.; Clare, S. E.; Halas, N. J., Nanoshell-Enabled Photothermal Cancer Therapy: Impending Clinical Impact. Acc. Chem. Res. 2008, 41, 1842-1851.
56. Drexhage, K. H., Influence of a dielectric interface on fluorescence decay time. J. Lumin. 1970, 1.2, 693-701.
57. Bardhan, R.; Grady, N. K.; Cole, J. R.; Joshi, A.; Halas, N. J., Fluorescence Enhancement by Au Nanostructures: Nanoshells and Nanorods. ACS Nano 2009, 3, 744-752.
58. Bardhan, R.; Chen, W.; Perez-Torres, C.; Bartels, M.; Huschka, R. M.; Zhao, L. L.; Morosan, E.; Pautler, R. G.; Joshi, A.; Halas, N. J., Nanoshells with Targeted Simultaneous Enhancement of Magnetic and Optical Imaging and Photothermal Therapeutic Response. Adv. Funct. Mater. 2009, 19, 3901-3909.
59. Bardhan, R.; Chen, W.; Bartels, M.; Perez-Torres, C.; Botero, M. F.; McAninch, R. W.; Contreras, A.; Schiff, R.; Pautler, R. G.; Halas, N. J.; Joshi, A., Tracking of Multimodal Therapeutic Nanocomplexes Targeting Breast Cancer in Vivo. Nano Lett. 2010, 10, 4920-4928.
60. Derfus, A. M.; Chen, A. A.; Min, D.-H.; Ruoslahti, E.; Bhatia, S. N., Targeted Quantum Dot Conjugates for siRNA Delivery. Bioconjugate Chem. 2007, 18, 1391-1396.
61. Tan, W. B.; Jiang, S.; Zhang, Y., Quantum-dot based nanoparticles for targeted silencing of HER2/neu gene via RNA interference. Biomaterials 2007, 28, 1565-1571.
62. Müller, R.; Hergt, R.; Zeisberger, M.; Gawalek, W., Preparation of magnetic nanoparticles with large specific loss power for heating applications. J. Magn. Magn. Mater. 2005, 289, 13-16.
63. Yoo, D.; Lee, J.-H.; Shin, T.-H.; Cheon, J., Theranostic Magnetic Nanoparticles. Acc. Chem. Res. 2011, 44, 863-874.
64. Sun, S.; Zeng, H.; Robinson, D. B.; Raoux, S.; Rice, P. M.; Wang, S. X.; Li, G., Monodisperse MFe2O4 (M = Fe, Co, Mn) Nanoparticles. J. Am. Chem. Soc. 2003, 126, 273-279.
65. Jang, J.-t.; Nah, H.; Lee, J.-H.; Moon, S. H.; Kim, M. G.; Cheon, J., Critical Enhancements of MRI Contrast and Hyperthermic Effects by Dopant-Controlled Magnetic Nanoparticles. Angew. Chem. Int. Ed. 2009, 48, 1234-1238.
66. Gao, W.; Chan, J. M.; Farokhzad, O. C., pH-Responsive Nanoparticles for Drug Delivery. Mol. Pharm. 2010, 7, 1913-1920.
67. Dressman, J. B.; Berardi, R. R.; Dermentzoglou, L. C.; Russell, T. L.; Schmaltz, S. P.; Barnett, J. L.; Jarvenpaa, K. M., Upper Gastrointestinal (GI) pH in Young, Healthy Men and Women. Pharm. Res. 1990, 7, 756-761.
68. Colombo, P.; Sonvico, F.; Colombo, G.; Bettini, R., Novel Platforms for Oral Drug Delivery. Pharm. Res. 2009, 26, 601-611.
69. Vaupel, P., Tumor microenvironmental physiology and its implications for radiation oncology. Semin. Radiat. Oncol. 2004, 14, 198-206.
70. Kim, J.-w.; Dang, C. V., Cancer's Molecular Sweet Tooth and the Warburg Effect. Cancer Res. 2006, 66, 8927-8930.
71. Murphy, R. F.; Powers, S.; Cantor, C. R., Endosome pH measured in single cells by dual fluorescence flow cytometry: rapid acidification of insulin to pH 6. J. Cell Biol. 1984, 98, 1757-1762.
72. Mukherjee, S., Ghosh, R. N., and Maxfield, F. R. Endocytosis. Physiol. Rev. 1997, 77, 759-803.
73. Needham, D.; Dewhirst, M. W., The development and testing of a new temperature-sensitive drug delivery system for the treatment of solid tumors. Adv. Drug Delivery Rev. 2001, 53, 285-305.
74. Feil, H.; Bae, Y. H.; Feijen, J.; Kim, S. W., Effect of comonomer hydrophilicity and ionization on the lower critical solution temperature of N-isopropylacrylamide copolymers. Macromolecules 1993, 26, 2496-2500.
75. Keerl, M.; Smirnovas, V.; Winter, R.; Richtering, W., Copolymer Microgels from Mono- and Disubstituted Acrylamides: Phase Behavior and Hydrogen Bonds. Macromolecules 2008, 41, 6830-6836.
76. Chatterjee, J.; Haik, Y.; Chen, C.-J., Size dependent magnetic properties of iron oxide nanoparticles. J. Magn. Magn. Mater. 2003, 257, 113-118.
77. Qin, J.; Asempah, I.; Laurent, S.; Fornara, A.; Muller, R. N.; Muhammed, M., Injectable Superparamagnetic Ferrogels for Controlled Release of Hydrophobic Drugs. Adv. Mater. 2009, 21, 1354-1357.
78. Hu, S.-H.; Chen, S.-Y.; Liu, D.-M.; Hsiao, C.-S., Core/Single-Crystal-Shell Nanospheres for Controlled Drug Release via a Magnetically Triggered Rupturing Mechanism. Adv. Mater. 2008, 20, 2690-2695.
79. Dreaden, E. C.; Mackey, M. A.; Huang, X.; Kang, B.; El-Sayed, M. A., Beating cancer in multiple ways using nanogold. Chem. Soc. Rev. 2011, 40, 3391-3404.
80. Weissleder, R., A clearer vision for in vivo imaging. Nat. Biotechnol. 2001, 19, 316-317.
81. American National Standards Institute, American National Standard for the safe use of lasers , ANSI Z136.1-1993. Laser Institute Orlando, FL 1993.
82. Link, S.; Wang, Z. L.; El-Sayed, M. A., How Does a Gold Nanorod Melt? J. Phys. Chem. B 2000, 104, 7867-7870.
83. Takahashi, H.; Niidome, Y.; Yamada, S., Controlled release of plasmid DNA from gold nanorods induced by pulsed near-infrared light. Chem. Commun. 2005, (17), 2247-2249.
84. Kang, H.; Trondoli, A. C.; Zhu, G.; Chen, Y.; Chang, Y.-J.; Liu, H.; Huang, Y.-F.; Zhang, X.; Tan, W., Near-Infrared Light-Responsive Core–Shell Nanogels for Targeted Drug Delivery. ACS Nano 2011, 5, 5094-5099.
85. Oldenburg, S. J.; Averitt, R. D.; Westcott, S. L.; Halas, N. J., Nanoengineering of optical resonances. Chem. Phys. Lett. 1998, 288, 243-247.
86. Park, H.; Yang, J.; Lee, J.; Haam, S.; Choi, I.-H.; Yoo, K.-H., Multifunctional Nanoparticles for Combined Doxorubicin and Photothermal Treatments. ACS Nano 2009, 3, 2919-2926.
87. Lee, S.-M.; Park, H.; Choi, J.-W.; Park, Y. N.; Yun, C.-O.; Yoo, K.-H., Multifunctional Nanoparticles for Targeted Chemophotothermal Treatment of Cancer Cells. Angew. Chem. Int. Ed. 2011, 50, 7581-7586.
88. Chen, J.; McLellan, J. M.; Siekkinen, A.; Xiong, Y.; Li, Z.-Y.; Xia, Y., Facile Synthesis of Gold−Silver Nanocages with Controllable Pores on the Surface. J. Am. Chem. Soc. 2006, 128, 14776-14777.
89. Yavuz, M. S.; Cheng, Y.; Chen, J.; Cobley, C. M.; Zhang, Q.; Rycenga, M.; Xie, J.; Kim, C.; Song, K. H.; Schwartz, A. G.; Wang, L. V.; Xia, Y., Gold nanocages covered by smart polymers for controlled release with near-infrared light. Nat. Mater. 2009, 8, 935-939.
90. Anand, P.; Kunnumakara, A.; Sundaram, C.; Harikumar, K.; Tharakan, S.; Lai, O.; Sung, B.; Aggarwal, B., Cancer is a Preventable Disease that Requires Major Lifestyle Changes. Pharm. Res. 2008, 25, 2097-2116.
91. Jemal, A.; Bray, F.; Center, M. M.; Ferlay, J.; Ward, E.; Forman, D., Global cancer statistics. CA Cancer J Clin. 2011, 61, 69-90.
92. Gu, Y. L., Spiritual Distress Experienced by Cancer Patients-Develop a Spiritual Care for Cancer Patients. TW. J. Hosp. Palliat. Care 2005, 10, 221-223.
93. Siegel, R.; Naishadham, D.; Jemal, A., Cancer statistics, 2012. C CA Cancer J Clin. 2012, 62, 10-29.
94. Schwartsmann, G.; Ratain, M. J.; Cragg, G. M.; Wong, J. E.; Saijo, N.; Parkinson, D. R.; Fujiwara, Y.; Pazdur, R.; Newman, D. J.; Dagher, R.; Di Leone, L., Anticancer Drug Discovery and Development Throughout the World. J Clin. Oncol. 2002, 20, 47-59.
95. Foster, N. I., Doxorubicin: Anticancer Antibiotics. Am. J Clin. Oncol. 1982, 5, 331.
96. Larsen, A. K.; Escargueil, A. E.; Skladanowski, A., Catalytic topoisomerase II inhibitors in cancer therapy. Pharmacol. Ther. 2003, 99, 167-181.
97. Green, P. S.; Leeuwenburgh, C., Mitochondrial dysfunction is an early indicator of doxorubicin-induced apoptosis. Biochim. Biophys. Acta 2002, 1588, 94-101.
98. Kintzel, P. E.; Dorr, R. T., Anticancer drug renal toxicity and elimination: dosing guidelines for altered renal function. Cancer Treat. Rev. 1995, 21, 33-64.
99. Jaracz, S.; Chen, J.; Kuznetsova, L. V.; Ojima, I., Recent advances in tumor-targeting anticancer drug conjugates. Bioorg. Med. Chem. 2005, 13, 5043-5054.
100. Schimmel, K. J. M.; Richel, D. J.; van den Brink, R. B. A.; Guchelaar, H.-J., Cardiotoxicity of cytotoxic drugs. Cancer Treat. Rev. 2004, 30, 181-191.
101. Gabizon, A.; Catane, R.; Uziely, B.; Kaufman, B.; Safra, T.; Cohen, R.; Martin, F.; Huang, A.; Barenholz, Y., Prolonged Circulation Time and Enhanced Accumulation in Malignant Exudates of Doxorubicin Encapsulated in Polyethylene-glycol Coated Liposomes. Cancer Res. 1994, 54, 987-992.
102. Gordon, A. N.; Fleagle, J. T.; Guthrie, D.; Parkin, D. E.; Gore, M. E.; Lacave, A. J., Recurrent Epithelial Ovarian Carcinoma: A Randomized Phase III Study of Pegylated Liposomal Doxorubicin Versus Topotecan. J. Clin. Oncol. 2001, 19, 3312-3322.
103. Bechet, D.; Couleaud, P.; Frochot, C.; Viriot, M.-L.; Guillemin, F.; Barberi-Heyob, M., Nanoparticles as vehicles for delivery of photodynamic therapy agents. Trends Biotechnol. 2008, 26, 612-621.
104. Triesscheijn, M.; Baas, P.; Schellens, J. H. M.; Stewart, F. A., Photodynamic Therapy in Oncology. Oncologist 2006, 11, 1034-1044.
105. Albert, A., Chemical Aspects of Selective Toxicity. Nature 1958, 182, 421-423.
106. Carl, P. L.; Chakravarty, P. K.; Katzenellenbogen, J. A., A novel connector linkage applicable in prodrug design. J. Med. Chem. 1981, 24, 479-480.
107. Andrew, L., Prodrugs. In Smith and Williams' Introduction to the Principles of Drug Design and Action, Fourth Edition, CRC Press: 2005; pp 211-232.
108. Song, C. W., Effect of Local Hyperthermia on Blood Flow and Microenvironment: A Review. Cancer Res. 1984, 44, 4721-4730.
109. Griffin, R. J.; Dings, R. P.; Jamshidi-Parsian, A.; Song, C. W., Mild temperature hyperthermia and radiation therapy: role of tumour vascular thermotolerance and relevant physiological factors. Int. J. Hyperthermia 2010, 26, 256-63.
110. Rybak, L. D., Fire and Ice: Thermal Ablation of Musculoskeletal Tumors. Radiol. Clin. North Am. 2009, 47, 455-469.
111. Goldberg, S. N., Radiofrequency tumor ablation: principles and techniques. Eur. J. Ultrasound 2001, 13, 129-147.
112. Liang, P.; Wang, Y., Microwave Ablation of Hepatocellular Carcinoma. Oncologist 2007, 72, 124-131.
113. Kennedy, J. E., High-intensity focused ultrasound in the treatment of solid tumours. Nat. Rev. Cancer 2005, 5, 321-327.
114. Manthe, R. L.; Foy, S. P.; Krishnamurthy, N.; Sharma, B.; Labhasetwar, V., Tumor Ablation and Nanotechnology. Mol. Pharm. 2010, 7, 1880-1898.
115. Adams, G. P.; Weiner, L. M., Monoclonal antibody therapy of cancer. Nat. Biotechnol. 2005, 23, 1147-1157.
116. Levy-Nissenbaum, E.; Radovic-Moreno, A. F.; Wang, A. Z.; Langer, R.; Farokhzad, O. C., Nanotechnology and aptamers: applications in drug delivery. Trends in Biotechnology 2008, 26, 442-449.
117. Brown K. C., Peptidic Tumor Targeting Agents: The Road from Phage Display Peptide Selections to Clinical Applications. Curr. Pharm. Des. 2010, 16, 1040-1054.
118. Sudimack, J.; Lee, R. J., Targeted drug delivery via the folate receptor. Adv. Drug Delivery Rev. 2000, 41, 147-162.
119. Shangguan, D.; Li, Y.; Tang, Z.; Cao, Z. C.; Chen, H. W.; Mallikaratchy, P.; Sefah, K.; Yang, C. J.; Tan, W., Aptamers evolved from live cells as effective molecular probes for cancer study. Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 11838-11843.
120. Timko, B. P.; Dvir, T.; Kohane, D. S., Remotely Triggerable Drug Delivery Systems. Adv. Mater. 2010, 22, 4925-4943.
121. Greenfield, R. S.; Kaneko, T.; Daues, A.; Edson, M. A.; Fitzgerald, K. A.; Olech, L. J.; Grattan, J. A.; Spitalny, G. L.; Braslawsky, G. R., Evaluation in Vitro of Adriamycin Immunoconjugates Synthesized Using an Acid-sensitive Hydrazone Linker. Cancer Res. 1990, 50, 6600-6607.
122. Xiao, Z.; Shangguan, D.; Cao, Z.; Fang, X.; Tan, W., Cell-Specific Internalization Study of an Aptamer from Whole Cell Selection. Chem. Eur. J. 2008, 14, 1769-1775.
123. Hahn, G. M.; Braun, J.; Har-Kedar, I., Thermochemotherapy: synergism between hyperthermia (42-43 degrees) and adriamycin (of bleomycin) in mammalian cell inactivation. Proc. Natl. Acad. Sci. U. S. A. 1975, 72, 937-940.
124. Choi, M.-R.; Stanton-Maxey, K. J.; Stanley, J. K.; Levin, C. S.; Bardhan, R.; Akin, D.; Badve, S.; Sturgis, J.; Robinson, J. P.; Bashir, R. et al., A Cellular Trojan Horse for Delivery of Therapeutic Nanoparticles into Tumors. Nano Lett. 2007, 7, 3759-3765.
125. Choi, K. Y.; Yoon, H. Y.; Kim, J.-H.; Bae, S. M.; Park, R.-W.; Kang, Y. M.; Kim, I.-S.; Kwon, I. C.; Choi, K.; Jeong, S. Y. et al., Smart Nanocarrier Based on PEGylated Hyaluronic Acid for Cancer Therapy. ACS Nano 2011, 5, 8591-8599.
126. Hamid, R.; Rotshteyn, Y.; Rabadi, L.; Parikh, R.; Bullock, P., Comparison of alamar blue and MTT assays for high through-put screening. Toxicol. in Vitro 2004, 18, 703-710.
127. Nikoobakht, B.; El-Sayed, M. A., Preparation and Growth Mechanism of Gold Nanorods (NRs) Using Seed-Mediated Growth Method. Chem. Mater. 2003, 15, 1957-1962.
128. Yu-Fen, H.; Yang-Wei, L.; Huan-Tsung, C., Growth of various Au–Ag nanocomposites from gold seeds in amino acid solutions. Nanotechnology 2006, 17, 4885-4894.
129. Orendorff, C. J.; Murphy, C. J., Quantitation of Metal Content in the Silver-Assisted Growth of Gold Nanorods. J. Phys. Chem. B 2006, 110, 3990-3994.
130. Kim, F.; Song, J. H.; Yang, P., Photochemical Synthesis of Gold Nanorods. J. Am. Chem. Soc. 2002, 124, 14316-14317.
131. Nikoobakht, B.; El-Sayed, M. A., Evidence for Bilayer Assembly of Cationic Surfactants on the Surface of Gold Nanorods. Langmuir 2001, 17, 6368-6374.
132. Yu; Chang, S.-S.; Lee, C.-L.; Wang, C. R. C., Gold Nanorods: Electrochemical Synthesis and Optical Properties. J. Phys. Chem. B 1997, 101, 6661-6664.
133. Hurst, S. J.; Lytton-Jean, A. K. R.; Mirkin, C. A., Maximizing DNA Loading on a Range of Gold Nanoparticle Sizes. Anal. Chem. 2006, 78, 8313-8318.
134. Chithrani, B. D.; Ghazani, A. A.; Chan, W. C. W., Determining the Size and Shape Dependence of Gold Nanoparticle Uptake into Mammalian Cells. Nano Lett. 2006, 6, 662-668.
135. Kuo, T.-R.; Hovhannisyan, V. A.; Chao, Y.-C.; Chao, S.-L.; Chiang, S.-J.; Lin, S.-J.; Dong, C.-Y.; Chen, C.-C., Multiple Release Kinetics of Targeted Drug from Gold Nanorod Embedded Polyelectrolyte Conjugates Induced by Near-Infrared Laser Irradiation. J. Am. Chem. Soc. 2010, 132, 14163-14171.
136. Park, J.-H.; von Maltzahn, G.; Xu, M. J.; Fogal, V.; Kotamraju, V. R.; Ruoslahti, E.; Bhatia, S. N.; Sailor, M. J., Cooperative nanomaterial system to sensitize, target, and treat tumors. Proc. Natl. Acad. Sci. U. S. A. 2009, 107, 981-986.
137. You, J.; Shao, R.; Wei, X.; Gupta, S.; Li, C., Near-Infrared Light Triggers Release of Paclitaxel from Biodegradable Microspheres: Photothermal Effect and Enhanced Antitumor Activity. Small 2010, 6, 1022-1031.