Chapter 8 Thermosensitive Yolk/Shell Capsules for Magnetically-Triggered Drug
8.9 Cell uptake and MR imaging
Cellular uptake of the FITC-labeled yolk/shell capsules was investigated using confocal microscopy. This study used a normal cell model of retinal pigment epithelium (RPE) cells (ARPE-19), which are from a monolayer of hexagonal cells separating the neural retina from the underlying choroidal vascular bed. Figures 8.7a
150
and 7b show cells incubated with FITC-labeled yolk/shell capsules for 4 and 24 hours, respectively. For the 4 hour incubation, some of the capsules appeared as green dots that were attached to the surface of the cell membranes; however, most of the capsules were still dispersed on the plate. Increasing the uptake time to 24 hours, shown in
Figure 8.7b, resulted in a greater adsorption of the FITC-labeled capsules onto the
cells, and some capsules also appeared to reside inside the cells. This implies that the yolk/shell capsules were gradually taken up by the cells, probably through endocytosis. The green fluorescent dye can be clearly observed in the cytoplasm. The capsules appear to be localized as discrete dots, suggesting that there was noFigure 8.7 Time-course confocal images of ARPE-19 cells incubated with 10 FITC-labeled yolk/shell capsules (green dots) for (a) 4 and (b) 24 hours. The cells were stained with rhodamine phalloidin (red), and cell nucleus with DAPI (blue). (c) The cross section images of cells viewed by laser-scanning confocal microscope exhibited that the capsules are localized in cells. (d) ARPE-19 cell viability under the incubation of capsules for 24 hours with and without 1-minute of magnetic field treatment. (e) Magnetic resonance images of rat brain before and after the intravenous injection of yolk/shell capsules. The local hyperintensity generated by capsules was visualized using a 3 T small animal MR. Image was acquired pre-injection (Left) and 2 hr post-injection (Right).
151
detectable leaching of dye from the capsules. The cross-section of the confocal images in Figure 8.7c demonstrates considerable regions of the cytoplasm displaying strong green fluorescence, suggesting that the capsules are efficiently localized within the cell.
The MTT (3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyl Tetrazolium Bromide) assay was used as a measure of the metabolic competence of the cells incubated with yolk/shell capsules, and the results are shown in Figure 8.7d. The nanocapsules were incubated with ARPE-19 cells for 24 hours and then subjected to a magnetic field for 1 min. The difference in the cytotoxicity seen before and after 1 min of magnetic field treatment is approximately 3% to 5%, and the cytotoxicity that was observed was likely caused by the magnetic heating. However, the magnetic field treatment is tolerable and the cell viability was still greater than 90%. These results demonstrate the relatively low cytotoxicity of these capsules under magnetic field treatment.
However, decreasing the magnetic field exposure time required to trigger drug release could decrease the cytotoxic effect of magnetic heating. This is an important goal for future research because low cytotoxicity is a critical requirement for drug delivery vehicles.
The small effect of the capsules on cell viability led us to study the capsules in vivo as MR imaging agents as shown in Figures 8.7e and 8.7f. Healthy rats were intravenously injected with yolk/shell capsules (12 mg/kg, 0.3 mL). Injection of the capsules enhanced the image contrast of MR images of rat brains and enabled the visualization of blood vessels, indicating that these yolk/shell capsules can serve as MRI contrast agents as well as drug delivery vehicles. These yolk/shell capsules provide an avenue for controlled drug delivery and offer a potential advantage for bioimaging and biomedical applications requiring drug release following physical rupture caused by external application of a magnetic field.
8.10 Summary
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In summary, yolk/shell capsules have been prepared with a soft thermosensitive core and a thin but dense silica shell. The dense silica shell acts as a barrier that restricts undesired drug leakage before triggering. Incorporating a small amount of magnetic nanoparticles into the core leaves a vast space for encapsulation of drug molecules, and the thermosensitive polymer exhibits a hydrophilic-to-hydrophobic transition at a characteristic temperature (CMT) that triggers a size contraction as large as 10 fold. The thermal sensitivity of these yolk/shell capsules enables magnetic triggering of capsule rupture in response to the heat induced by the external magnetic field. In this system, the iron oxide nanoparticles act as the energy absorbers, achieving rapid triggered drug release that is not available from conventional yolk/shell particles and inorganic capsules. These capsules were efficiently taken up by healthy cell lines, and the cells maintain good viability under magnetic field treatment. In vivo MR imaging of rat brains showed that the yolk/shell capsules can clearly enhance image contrast after injection. Future development of this new class of functional yolk/shell capsules includes targeted imaging and therapy in vitro and in vivo, and we envision that this enabling technology will open exciting opportunities in nanomedicine and biotechnology.
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Chapter 9 Conclusion
9.1 Ferrogels for magnetically-triggered drug release
1. Ferrogel fabricated by incorporating iron oxide NPs and gelatin/chitosan exhibited the fast response of drug release while applying a high frequency magnetic field (HFMF).
2. XPS and SEM demonstrated the strong interactions between carboxylic acid groups of gelatin and iron oxide NPs.
3. Burst release of drug from the ferrogels is optimized with the incorporation of 40 nm iron oxide nanoparticles under high-frequency magnetic field.
4. While applying cyclic short-time exposure of the ferrogels to HFMF, the stimulating response can be controlled and repeatedly reproduced as a result of a consecutive burst release profile of drug.
9.2 Core/single-crystal iron oxide shell nanospheres for drug delivery
1. Core-shell nanosphere with PVP-modified silica core following a functional deposition of a single-crystal iron oxide shell was fabricated.
2. The ultrathin iron oxide shell offers a surprisingly outstanding controlled release and non-release behavior for the molecules encapsulated inside the silica core.
3. The dense, single crystalline shell is efficiently preventing the fluorescence dye from un-desired release, giving that an undesirable leakage of the molecule during the course of delivery is completely inhibited.
4. The molecules encapsulated in the core can be released with a highly controllable manner, through the use of a magnetic stimulus.
5. The multifunctional drug delivery nanodevice was composed of core-iron oxide
154
shell carriers and quantum dots to image, target, and deliver drugs via remote control.
5. These nanodevices offer outstanding control of release and retention for the molecules encapsulated inside their polymer core.
6. Multifunctional nanodevices are able to monitor real-time drug dosage through corresponding variation in emission spectrum of the quantum dots within the HeLa cells.
7. With the in-situ monitoring capability of the nanodevice, we believe that both target-oriented therapy and diagnosis can be integrated and managed within a single cell.
9.3 Self-assemble iron oxide/silica (SAIO) core-shell carriers
1. The core-shell nanocarriers are able to well-disperse easily in an aqueous solution without using any interfacial molecules for stabilization.
2. The ultra-thin, 4-5 nm, outer silica shell coated on the SAIO core, a mixture of iron oxide nanoparticles and PVA, blocked the drug molecules effectively from therapeutically undesirable release from the core phase before subjecting to magnetic stimulation.
3. Under high-frequency magnetic field (HFMF) treatment, the SAIO@SiO2 nanocarriers displayed a fast-acting and precise stimulus-time-dependent dosing response to the environment and restored to original state.
4. SAIO@SiO2 nanocarriers were allowed a high efficiency uptake by HeLa cells within dozens of minutes and have been shown to exhibit excellent cytocompatibility, implying the nanocarriers are potentially capable of offering high-efficient cellular-based delivery following a fast-acting, accurate release of therapeutic agents for anti-cancer applications.
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9.4 Thermosensitive yolk/shell capsules
1. The dense silica shell of capsules acts as a barrier that restricts undesired drug leakage before triggering.
2. Incorporating a small amount of magnetic nanoparticles into the core leaves a vast space for encapsulation of drug molecules, and the thermosensitive polymer exhibits a hydrophilic-to-hydrophobic transition at a characteristic temperature (CMT) that triggers a size contraction as large as 10 fold.
3. The thermal sensitivity of these yolk/shell capsules enables magnetic triggering of capsule rupture in response to the heat induced by the external magnetic field.
4. The iron oxide nanoparticles act as the energy absorbers, achieving rapid triggered drug release that is not available from conventional yolk/shell particles and inorganic capsules.
5. These capsules were efficiently taken up by healthy cell lines, and the cells maintain good viability under magnetic field treatment.
6. In vivo MR imaging of rat brains showed that the yolk/shell capsules can clearly enhance image contrast after injection.
156
Reference
[1] A. C. R. Grayson, I. S. Choi, B. M. Tyler, P. P. Wang, H. Brem, M. J. Cima, R.
Langer, Nature Materials 2003, 2, 767.
[2] Z. Hu, X. Xia, Adv. Mater. 2004, 16, 305.
[3] X. Z. Zhang, D. Q. Wu, C. C. Chu, Biomaterials 2004, 25, 3793.
[4] M. Das, S. Mardyani, W. C. W. Chan, E. Kumacheva, Adv. Mater. 2006, 18, 80.
[5] M. R. Abidian, D. H. Kim, D. C. Martin, Adv. Mater. 2006, 18, 405.
[6] B. G. De Geest, A. G. Skirtach, A. A. Mamedov, A. A. Antipov, N. A. Kotov, S. C.
De Smedt, G. B. Sukhorukov, Small 2007, 3, 804.
[7] H. J. Kim, H. Matsuda, H. Zhou, I. Honma, Adv. Mater. 2006, 18, 3083.
[8] E. R. Edelman, J. Kost, H. Bobeck, R. Langer, J. Biomed. Mater. Res. 1985, 19, 67.
[9] J. Kost, J. Wolfrum, R. Langer, J. Biomed. Mater. Res. 1987, 21, 1367.
[10] J. Kost, R. Noecker, E. Kunica, R. Langer, J. Biomed. Mater. Res. 1985, 19, 935.
[11] Z.vLu, M. D. Prouty, Z. Guo, V. O. Golub, C. S. S. R. Kumar, Y. M. Lvov,
Huh, S. Haam, Adv. Mater. 2009, 21, 4339– 4342.
[15] M. S. Yavuz, Y. Cheng, J. Chen, C. M. Cobley, Q. Zhang, M. Rycenga, J. Xie, C.
Kim, K. H. Song, A. G. Schwartz, L. V. Wang, Y. Xia, Nature Materials, 2009, 8, 935– 939.
[16] Z. Liu, A. C. Fan, K. Rakhra, S. Sherlock, A. Goodwin, X. Chen, Q. Yang, D. W.
Felsher, H. Dai, Angew. Chem. Int. Ed. 2009, 48, 7668 –7672.
[17] W. S. Kuo, C. N. Chang, Y. T. Chang, M. H. Yang, Y. H. Chien, S. J. Chen, C. S.
Yeh, Angew. Chem. Int. Ed. 2010, 49, 2711– 2715.
[18] D. V. Volodkin, A. G. Skirtach, H. Möhwald, Angew. Chem. Int. Ed. 2009, 48, 1807– 1809.
[19] S. H. Hu, S. Y. Chen, D. M. Liu, C. S. Hsiao, Adv. Mater. 2008, 20, 2690– 2695.
[20] S. H. Hu, T. Y. Liu, D. M. Liu, S. Y. Chen, Macromolecules 2007, 40, 6786–
6788.
[21] H. Rosen, T. Abribat, Nature Reviews Drug Discovery 2005, 4, 381.
[22] K. E. Uhrich, S.M. Cannizzaro, R. S. Langer, K.M. Shakesheff, Chemical Reviews, 1999, 99, 3181.
157
[23] L.Y. Chu, Y. Li, J.H. Zhu, H.D. Wang, Y.J. Liang, Journal of Controlled Release
2004, 97, 43.
[24] L. Chen, M.e Liu, H. Bai, P. Chen, F. Xia, D. Han, L. Jiang, J. Am. Chem. Soc.
2009, 131, 10467.
[25] S. Q. Liu, Y. Y. Yang, X. M. Liu, Y. W. Tong, Biomacromolecules 2003, 4, 1784.
[26] L. Bromberg, M. Temchenko, G. D. Moeser, T. A. Hatton, Langmuir, 2004, 20, 5683.
[27] C. Alvarez-Lorenzo, S. Deshmukh, L. Bromberg, T. A. Hatton, I. Sández-Macho, A. Concheiro, Langmuir, 2007, 23, 11475.
[28] K. Mortensen, J. Phys.: Condens. Matter 1996, 8, A13.
[29] P. Alexandridis, et al., Macromolecules 1994, 27, 2414.
[30] P. Alexandridis, et al., Langmuir 1995, 11, 1468.
[31] S. H. Choi, J. H. Lee, S. M. Choi, T. G. Park, Langmuir 2006, 22, 1758.
[32] A. I. Van D. Bulcke, B. Bogdanov, N. De Rooze, E. H. Schacht, M. Cornelissen, H. Berghmans, Biomacromolecules 2000, 1, 31.
[33] T. Mitsumata, K. Ikeda, J.P. Gong, Y. Osada, D. Szabó, M. Zrínyi, J. Applied Phys., 1999, 85, 8451.
[34] P.M. Xulu, G. Filipcsei, M. Zrínyi, Macromolecules 2000, 33, 1716.
[35] M. Zrínyi, D. Szabó, H.G. Kilian, Polymer Gels and Networks, 1998, 6, 441.
[36] O. Saslawski, C. Weingarten, J.P. Benoit, P. Couvreur, Life Science, 1998, 42, 1521.
[37] A.vK. Gupta, M. Gupta, Biomaterials 2005, 26, 3995.
[38] T. Neuberger, B. Schöpf, H. Hofmann, M. Hofmann, B.V. Rechenberg, J. Magn.
Mag. Mat. 2005, 293, 483.
[39] J. Fricker, F. Writer, Drug Delivery Today, 2001, 6, 387.
[40] T. Y. Liu, S. H. Hu, K. H. Liu, D. M. Liu, S. Y. Chen, J. Magn. Magn. Mater.
2006, 304, e397.
[41] X. Z. Zhang, Y. Y. Yang, T. S. Chung, K. X. Ma, Langmuir 2001, 17, 6094.
[42] T. D. Dziubla, M. C. Torjman, J. I. Joseph, M. Murphy-Tatum, A. M. Lowman, Biomaterials 2001, 22, 2893.
[43] H. Storrie, D. J. Mooney, Advanced Drug Delivery Reviews 2006, 58, 500.
[44] O. C. Farokhzad, R. Langer, ACS nano 2009, 3, 16.
[45] M. Bruchez, Jr., M. Moronne, P. Gin, S. Weiss, A. P. Alivisatos, Science 1998, 281, 2013.
[46] W. C. Chan, S. Nie, Science 1998, 281, 2016.
[47] K. Balasubramanian, M. Burghard, Small 2005, 1, 180.
[48] L. Lacerda, A. Bianco, M. Prato, K. Kostarelos, Adv. Drug Delivery Rev. 2006, 58, 1460.
158
[49] L. R. Hirsch, A. M. Gobin, A. R. Lowery, F. Tam, R. A. Drezek, N. J. Halas, J. L.
West, Ann. Biomed. Eng. 2006, 34, 15.
[50] D. L. Thorek, A. K. Chen, J. Czupryna, A. Tsourkas, Ann. Biomed. Eng. 2006, 34, 23.
[51] M. Ferrari, Nat. Rev. Cancer 2005, 5, 161.
[52] P. Grodzinski, M. Silver, L. K. Molnar, Expert Rev. Mol. Diagn. 2006, 6, 307.
[53] S. K. Sahoo, S. Parveen, J. J. Panda, Nanomedicine 2007, 3, 20.
[54] K. B. Keys, F. M. Andreopoulos, N. A. Peppas, Macromolecules 1998, 31, 8149.
[55] V. P. Torchilin, Adv. Drug Delivery Rev. 2006, 58, 1532.
[56] J. Chen, H. Park, K. Park, Proc. Int. Symp. Control. Rel. Bioact. Mater. 1998, 25, 60.
[57] W. Cai, X. Chen, Small 2007, 3, 1840.
[58] S. Liu, R. Maheshwari, K. L. Kiick, Macromolecules 2009, 42, 3.
[59] M. Arruebo, R. Fernández-Pacheco, M. R. Ibarra, J. Santamaría, NanoToady
2007, 2, 22.
[60] S. J. Lee, J. R. Jeong, S. C. Shin, J. C. Kim, Y. H. Chang YH, et al. J. Magn.
Magn. Mater. 2004, 272, 2432.
[61] D. L. J. Thorek, A. Chen, J. Czupryna, A. Tsourkas, Ann Biomed Eng 2006, 34, 23.
[62] C. H. Griffiths, M. P. Ohoro, T. W. Smith, J. Appl. Phys. 1979, 50, 7108.
[63] C. B. Murray, D. J. Norris, M. G. Bawendi, J. Am. Chem. Soc. 1993, 115, 8706.
[64] Z. A. Peng, X. G. Peng, J. Am. Chem. Soc. 2001, 123, 183.
[65] L. H. Qu, Z. A. Peng, X. G. Peng, Nano Lett 2001, 1, 333.
[66] M. A. Hines, P. Guyot-Sionnest, J. Phys. Chem. 1996, 100, 468.
[67] X. G. Peng, M. C. Schlamp, A. V. Kadavanich, A. P. Alivisatos, J. Am. Chem. Soc.
[70] M. Green. Chem. Commun. 2005, 24, 3002.
[71] U. Jeong, X. W. Teng, Y. Wang, H. Yang, Y. N. Xia, Adv. Mater. 2007, 19, 33.
159
583.
[76] L. L. Muldoon, M. Sandor, K. E. Pinkston, E. A. Neuwelt, Neurosurgery 2005, 57, 785.
[77] D. E. Sosnovik, M. Nahrendorf, R. Weissleder, Circulation 2007, 115, 2076.
[78] H. S. Choi, W. Liu, P. Misra, E. Tanaka, J. P. Zimmer, et al. Nat Biotechnol. 2007, 25, 1165.
[79] R. Weissleder, A.S . Lee, A.J . Fischman, P.Reimer , T.Shen, R. Wilkinson, R.J . Callahan, T. J. Brady, Radiology 1991, 181, 245.
[80] J.W.M. Bulte, D.L. Kraitchman, NMR Biomed. 2004, 17, 484.
[81] Y. X. J. Wang, S. M. Hussain, G. P. Krestin, Eur. Radiol. 2001, 11, 2319.
[82] M. F. Bellin, Eur. J. Radiol. 2006, 60, 314.
[83] R.W eissleder, A. Moore , U. Mahmood, R. Bhorade , H. Benveniste, E. A.
Chiocca, J. P. Basilion, Nat. Med. 2000, 6, 351.
[84] M. Zhao , D. A. Beauregard, L. Loizou, B. Davletov , K. M. Brindle, Nat. Med.
[87] T. Hyeon, Chem. Commun. 2003, 927.
[88] J. Park, K. An, Y. Hwang, J. G. Park, H. J. Noh, J. Y. Kim, J. H. Park, N.M.
Hwang, T. Hyeon, Nat. Mater. 2004, 3, 891.
[89] N. R. Jana, Y. Chen, X. Peng, Chem. Mater. 2004, 16, 3931.
160
Chem. Soc. 2005, 127, 9992.
[99] M. P. Morales , S. Veintemillas-Verdaguer, M. I. Montero, C. J. Serna, Chem.
Mater. 1999, 11, 3058.
[100] E. V. Shevchenko, D. V. Talapin, A. L. Rogach, A. Kornowski, M. Haase, H.
Weller, J. Am. Chem. Soc. 2002, 124, 11480.
[101] C. W. Jung, P. Jacobs, Magn. Reson. Imaging 1995, 13, 661.
[102] D. Hogemann, L. Josephson, R. Weissleder, J. P. Basilion, Bioconjug. Chem.
2000, 11, 941.
[103] R. Weissleder, A. Moore, U. Mahmood, R. Bhorade, H. Benveniste H, et al. Nat.
Med. 2000, 6, 351.
[109] A. K. Gupta, R. R. Naregalkar, V. D. Vaidya, M. Gupta. Nanomedicine 2007, 2, 23.
[110] X. H. Gao, Y. Y. Cui, R. M. Levenson, L. W. K. Chung, S. M. Nie, Nat.
Biotechnol. 2004, 22, 969.
[111] T. Pellegrino, L. Manna, S. Kudera, T. Liedl, D. Koktysh, et al. Nano Lett 2004, 4, 703.
[112] A. P. Philipse, M. P. B. Vanbruggen, C. Pathmamanoharan, Langmuir 1994, 10, 92.
[113] Y. Lu, Y. D. Yin, B. T. Mayers, Y. N. Xia, Nano Lett. 2002, 2, 183.
[114] M. Arruebo, et al., Chem. Mater. 2006, 18, 1911.
[115] R. Duncan, Materials Today 2005, 8, 16.
[116] U. Gaur, et al., Int. J. Pharmacol. 2000, 202, 1.
[117] T. Neuberger, et al., J. Magn. Magn. Mater. 2005, 293, 483.
[118] X.Wu, H. Liu, J. Liu, K. N. Haley, J. A. Treadway, J. P. Larson, N. Ge, F. Peale, M. P. Bruchez, Nat. Biotechnol. 2003, 21, 41.
[119] X. Gao , Y. Cui, R. M. Levenson, L.W. K. Chung, S. Nie, Nat. Biotechnol. 2004, 22, 969.
[120] D. B. Robinson, H. H. J. Persson , H. Zeng , G. Li, N. Pourmand, S. Sun, S. X.
Wang, Langmuir 2005, 21, 3096.
[121] N. Nitin, L. E. Laconte, O. Zurkiya, X. Hu, G. Bao, J. Biol. Inorg. Chem. 2004,
161
[127] A. S. Lubbe, C. Alexiou, C. Bergemann, J. Surg. Res. 2001, 95, 200.
[128] A. S. Lubbe, C. Bergemann, H. Riess, F. Schriever, P. Reichardt, et al. Cancer Res. 1996, 56, 4686.
Langer, D. S. Kohane, Nano Lett. 2009, 9, 3651.
[135] D. H. Kim, E. A. Rozhkova, I. V. Ulasov, S. D. Bader, T. Rajh, M. S. Lesniak,
[139] J. Kost, J. Wolfrum, R. Langer, R. J. Biomed. Mater. Res. 1987, 21, 1367.
[140] E. R. Edelman, J. Kost, H. Bobeck, R. Langer, J. Biomed. Mater. Res. 1985, 19, 67.
[141] O. Saslawski, C. Weingarten,J. P. Benoit, P. Couvreur, Life Sci. 1988, 42, 1521-1528.
[142] Z. Lu, M. D. Prouty, Z. Guo, V. O. Golub, C. S. S. R. Kumar, Y. M. Lvov, Langmuir 2005, 21, 2042.
[143] T. Y. Liu, S. H. Hu, T. Y. Liu, D. M. Liu, S. Y. Chen, Langmuir 2006, 22, 5974.
162
[144] Ting-Yu Liu, Shang-Hsiu Hu, Kun-Ho Liu, Dean-Mo Liu, San-Yuan Chen, J.
Controlled Release, 2008, 126, 228.
[145] V. Crescenzi, A. Francescangeli, A. Taglienti, Biomacromolecules 2002, 3, 1384.
[146] A. I. V. D. Bulcke, B. Bogdanov, N. D. Rooze, E. H. Schacht, M. Cornelissen, H.
Berghmans, Biomacromolecules 2000, 1, 31-38.
[147] H.Nakamura,W. Kato, M. Uehara, K. Nose, T. Omata, S. Otsuka-Yao-Matsuo, M. Miyazaki, H. Maeda, Chem. Mater. 2006, 18, 3330.
[148] W. Jiang, S. Mardyani, H. Fischer, W. C. W. Chan, Chem. Mater. 2006, 18, 872.
[149] P. S. Low, W. A. Henne, D. D. Doorneweerd, Acc. Chem. Res. 2008, 41, 120.
[150] A. Corma, U. Díaz, M. Arrica, E. Fernández, Í. Ortega, Angew. Chem. Int. Ed.
2009, 48, 6247.
[151] Y. Lu, Y. Zhao, L. Yu, L. Dong, C. Shi, M. J. Hu, Y. J. Xu, L. P. Wen, S. H. Yu, Adv. Mater. 2010, 22, 1407.
[152] Y. Yin, R. M. Rioux, C. K. Erdonmez, S. Hughes, G. A. Somorjai, A. P.
Alivisatos, Science 2004, 304, 711.
[153] Y. Sun, Y. Xia, Science 2002, 2176.
[154] X. J. Xu, D. Xu, J. Am. Chem. Soc. 2009, 131, 2774.
[155] X. J. Xu, D. Xu, Adv. Mater. 2010, 22, 1516.
[156] J. Yang, J. Lee, J. Kang, S. J. Oh, H. J. Ko, J. H. Son, K. Lee, J. S. Suh, Y. M.
Huh, S. Haam, Adv. Mater. 2009, 21, 4339.
[157] M. S. Yavuz, Y. Cheng, J. Chen, C. M. Cobley, Q. Zhang, M. Rycenga, J. Xie, C.
Kim, K. H. Song, A. G. Schwartz, L. V. Wang, Y. Xia, Nature Materials, 2009, 8, 935.
[158] S. H. Choi, J. H. Lee, S. M. Choi, T. G. Park, Langmuir 2006, 22, 1758– 1762.
[159] T. Y. Liu, K. H. Liu, D. M. Liu, S. Y. Chen, I. W. Chen, Adv. Funct. Mater. 2009, 19, 616.
[160] Y. Tian, P. Ravi, L. Bromberg, T. A. Hatton, K. C. Tam, Langmuir 2007, 23, 2638.
163
CURRICULUM VITAE
Shang-Hsiu Hu, Ph. D. Candidate
Add: 1001 Ta Hsueh Road, Hsinchu, Taiwan 30049, ROC Phone: +886-3-5712121#55394
E-mail: [email protected]
Education
Visiting Scholar, Department of Bioengineering, University of Washington, USA, 2009.5~2010.5.
Ph.D., Material Science and Engineering, National Chiao Tung University, Taiwan, ROC, 2006~2010.
M.S., Material Science and Engineering, National Chiao Tung University, Taiwan, ROC, 2004~2006.
B.S., Chemical Engineering, National Chung-Hsin University, Taiwan, ROC, 2000~2004.
Research Interests
1. Novel process development and controlled drug release in nano-biomaterial composites such as iron oxide nanoparticles, quantum dots and mesoporous silica.
2. Multifunctional nanomaterials for bioengineering and bioimaging.
3. Controlled rupture of novel core-shell spheres for drug delivery system which is able to be remotely controlled its rupturing behavior upon an external stimulation.
Selected Publications
1. Shang-Hsiu Hu, and Xiaohu Gao, "Nanocomposites with Spatially Separated Functionalities for Combined Imaging and Magnetolytic Therapy", J. Am. Chem. Soc., 2010, 7234-7237.
2. Shang-Hsiu Hu, San-Yuan Chen, Chi-Sheng Hsiao and Dean-Mo Liu, “Core/Single-Crystal-Shell Nanospheres for Controlled Drug Release via a Magnetically Triggered Rupturing Mechanism”, Adv. Mat., 2008, 20, 2690-2695.
3. Shang-Hsiu Hu, Wei-Lin Tung, Chen-Fu Liao, Dean-Mo Liu and San-Yuan Chen, Surfactant-free,
“Self-Assemble PVA-Iron Oxide /Silica Core-Shell Nanocarriers for High-Sensitive Magnetically Controlled Drug Release and Ultra-high Cancer Cell Uptake Efficiency”, Adv. Func. Mat., 2008, 18, 2946-2955.
4. Shang-Hsiu Hu, Kuan-Ting Kuo, Dean-Mo Liu, and San-Yuan Chen. “Synthesis of Drug Delivery Nano-device capable of Imagining, Targeting, and Self-Monitoring of Drug Release in Cancerous Cells”, Adv. Func. Mat., 2009, 19, 3396.
164
5. Shang-Hsiu Hu, Ting-Yu Liu, Dean-Mo Liu and San-Yuan Chen, “Controlled Pulsatile Drug Release from a Ferrogel by a High-Frequency Magnetic Field”, Macromolecules, 2007, 40, 6786-6788.
Honors
1. Silver medal of “National Innovation Award” for Biotechnology and Medicine Industry, 2008, Taiwan. (2008 國家新創獎 第二名)
2. Gold medal of “Creative Design and Implementation Competition on Biomedical Engineering”, 2008, Taiwan. (2008 醫學工程創意競賽 優勝)
3. Gold medal of “Taiwan Nano-Image Competition”, 2008, Taiwan.
(2008 台灣奈米影像攝影競賽 第一名)
4. Gold and copper medal of “Taiwan Nano-Image Competition”, 2009, Taiwan.
(2009 台灣奈米影像攝影競賽 第一名、第三名)
a. News by Material Views (2009-04-28): Magnetic Triggering of Drug Release with Precise and Localised Dosage. http://www.materialsviews.com/matview/display/en/352/TEXT
b. News by Material Views (2008-08-07): Magnetically Controlled Drug Release.
http://www.materialsviews.com/matview/display/en/739/TEXT c. News by NPG Asia Materials (2008-09-24): Magnetic precision http://www.natureasia.com/asia-materials/highlight.php?id=261
Publications
1. Shang-Hsiu Hu, and Xiaohu Gao, "Nanocomposites with Spatially Separated Functionalities for Combined Imaging and Magnetolytic Therapy", J. Am. Chem. Soc., 2010, 7234-7237.
2. Shang-Hsiu Hu, and Xiaohu Gao, "Stable Encapsulation of QD Barcodes with Silica Shells", Adv.
Func. Mat., 2010, Accepted.
3. Kuan-Ting Kuo, Shang-Hsiu Hu, Dean-Mo Liu, and San-Yuan Chen. “Magnetically-induced Synthesis of Highly-Crystalline Ternary Semiconductor Chalcopyrite Nanocrystals via a Magnetic Doping at Ambient Conditions”, Journal of Chemistry Materials, 2010, 20, 1744-1750.
4. Shang-Hsiu Hu, Kuan-Ting Kuo, Wei-Lin Tung, Dean-Mo Liu, and San-Yuan Chen. “Synthesis of Drug Delivery Nano-device capable of Imagining, Targeting, and Self-Monitoring of Drug Release in Cancerous Cells”, Adv. Func. Mat., 2009, 19, 3396.
5. Wei-Chen Huang, Shang-Hsiu Hu, Kun-Ho Liu, San-Yuan Chen and Dean-Mo Liu. “A Flexible Drug Delivery Chip for Magnetically-Controlled Release of Anti-Epileptic Drug”, Journal of Controlled Drug Release, 2009, 139, 221-228.
6. Ting-Yu Liu, Shang-Hsiu Hu, Dean-Mo Liu, San-Yuan Chen, and I-Wei Chen, Biomedical
165
Nanoparticle Carriers with Combined Thermal and Magnetic Responses, NanoToday, 2009, 4, 52-69 ( invited review).
7. Shang-Hsiu Hu, Ting-Yu Liu, Hsin-Yang Huang, Dean-Mo Liu, and San-Yuan Chen,
“Stimuli-Responsive Controlled Drug Release from Magnetic-Sensitive Silica Nanospheres”, J.
Nanosci. Nanotechnol., 2009, 9, 866-870.
8. Shang-Hsiu Hu, Chia-Hui Tsai, Chen-Fu Liao, Dean-Mo Liu and San-Yuan Chen, “Controlled Rupture of Magnetic Polyelectrolyte Microcapsules for Drug Delivery”, Langmuir, 2008, 24, 11811–11818.
9. Shang-Hsiu Hu, Wei-Lin Tung, Chen-Fu Liao, Dean-Mo Liu and San-Yuan Chen, Surfactant-free,
“Self-Assemble PVA-Iron Oxide /Silica Core-Shell Nanocarriers for High-Sensitive Magnetically Controlled Drug Release and Ultra-high Cancer Cell Uptake Efficiency”, Adv. Func. Mat., 2008, 18, 2946-2955.
10. Shang-Hsiu Hu, San-Yuan Chen, Chi-Sheng Hsiao and Dean-Mo Liu, “Core/Single-Crystal-Shell Nanospheres for Controlled Drug Release via a Magnetically Triggered Rupturing Mechanism”, Adv. Mat., 2008, 20, 2690-2695.
11. Ting-Yu Liu, Shang-Hsiu Hu, Kun-Ho Liu, Dean-Mo Liu and San-Yuan Chen, Instantaneous Drug Delivery of Magnetic/Thermal Sensitive Nanospheres by a High Frequency Magnetic Field, Langmuir, 2008, 24, 13306-13311.
12. Ting-Yu Liu, Shang-Hsiu Hu, Kun-Ho Liu, Dean-Mo Liu and San-Yuan Chen, “Study on controlled drug permeation of magnetic-sensitive ferrogels: Effect of Fe3O4 and PVA ”, Journal of Controlled Drug Release, 2008, 126, 228-236.
13. Shang-Hsiu Hu, Ting-Yu Liu, Hsin-Yang Huang, Dean-Mo Liu and San-Yuan Chen,
“Magnetic-Sensitive Silica Nanospheres for Controlled Drug Release”, Langmuir, 2008, 23, 239.
14. Ting-Yu Liu, Li-Ying Huang, Shang-Hsiu Hu, Ming-Chien Yang and San-Yuan Chen, Core-shell magnetic nanoparticles of heparin conjugate as recycling anticoagulants, J. Biomed.
Nanotechnol., 2007, in press.
15. Shang-Hsiu Hu, Ting-Yu Liu, Dean-Mo Liu and San-Yuan Chen, “Controlled Pulsatile Drug Release from a Ferrogel by a High-Frequency Magnetic Field”, Macromolecules, 2007, 40(19), 6786-6788.
16. Shang-Hsiu Hu, Ting-Yu Liu, Dean-Mo Liu and San-Yuan Chen, “Nano- Ferrosponges For Controlled Drug Release”, Journal of Controlled Drug Release, 2007, 121 (3), 181-189.
17. Shang-Hsiu Hu, Ting-Yu Liu, Chia-Hui Tsai, Dean-Mo Liu and San-Yuan Chen, “Preparation and Characterization of magnetic ferroscaffolds for tissue engineering”, Journal of Magnetism and Magnetic Materials, 2007, 310(2), 2871-2873.
18. Ting-Yu Liu, Shang-Hsiu Hu, Sheng-Hsiang Hu, Szu-Ping Tsai and San-Yuan Chen, “Preparation and characterization of thermal-sensitive ferrofluids for drug delivery application ”, Journal of Magnetism and Magnetic Materials, 2007, 310 (2), 2850-2852.
19. Ting-Yu Liu, Shang-Hsiu Hu, Tse-Ying Liu, Dean-Mo Liu and San-Yuan Chen,” Magnetic-sensitive