臺灣博碩士論文加值系統

摘要
奈米材料在不同產業的應用近年來已受到世界各國普遍的重視，最近國內在奈米生醫材料的研發上也有相當傑出的成果，然而對氧化矽與幾丁聚醣奈米複合顆粒於包覆食品成分的應用研究則相當少見。
本研究首先探討在弱酸的環境與幾丁聚醣的存在下矽酸鈉聚合形成氧化矽-幾丁聚醣奈米顆粒。當添加幾丁聚醣於矽酸鈉溶液中會劇烈增加矽酸鈉溶液的濁度及氧化矽奈米顆粒的平均水動力直徑。氧化矽形成的初期接近四級反應，之後膠狀的奈米顆粒轉變為慢速聚集的指數粒徑成長模式。幾丁聚醣的添加並沒有明顯改變氧化矽形成的速率，但是幾丁聚醣的添加卻容易使氧化矽奈米顆粒聚集更快，而形成更巨大的團簇。掃描式電子顯微鏡顯示合成氧化矽-幾丁聚醣複合奈米顆粒為3維成長並且會在更短的時間聚合成團。另外原子力學顯微鏡也證明氧化矽-幾丁聚醣複合奈米顆粒粒徑隨時間的增加而增加（在1小時和24小時的反應時間後，分別從1 nm成長到32 nm）。X射線繞射、紅外線光譜分析和元素分析確認這些奈米顆粒是由非晶形氧化矽和幾丁聚醣合成。氧化矽-幾丁聚醣奈米顆粒的合成提供一種可改進其功能特性的方法。
由於非晶形氧化矽易於生產和低成本，使得氧化矽常被使用於診斷和生物醫學研究。氧化矽一般被認為是安全的，因為其用於食品或者動物飼料成分已經被批准，但是最近的文獻顯示非晶形的氧化矽在高劑量下可能會有毒性，我們預測將來人們暴露於氧化矽中的機會會增加，所以我們要謹慎試驗氧化矽對於不同細胞的毒性並且想出新方法以解決相關問題。因此，本研究接著觀察非晶形的氧化矽奈米顆粒及幾丁聚醣-氧化矽奈米複合顆粒於低至高劑量的環境對於幾種正常纖維母細胞和腫瘤細胞的影響。細胞存活率分析結果顯示非晶形的氧化矽奈米顆粒於低劑量時並無細胞毒性，但在高劑量時則略微降低細胞的存活率。乳酸脫氫酶試驗也發現高劑量的氧化矽奈米顆粒會促使細胞膜損傷。同時比較細胞存活率與乳酸脫氫酶試驗發現纖維母細胞比腫瘤細胞更容易受到氧化矽奈米顆粒的傷害。另外，氧化矽-幾丁聚醣奈米複合顆粒則對細胞不致產生明顯的傷害。這項研究表示氧化矽奈米顆粒於高劑量下可能變得對人類細胞有毒，但是其細胞毒性可以藉由幾丁聚醣的修飾而顯著降低。
樟芝是台灣相當著名的中草藥，樟芝可以用來治療多種疾病像是食品或藥物中毒、腹瀉、腹部疼痛、高血壓、皮膚癬及肝癌等。本研究最後是評估利用幾丁聚醣與氧化矽包覆樟芝萃取物多醣形成奈米顆粒的可行性、其抗氧化性與對於正常細胞和腫瘤細胞的細胞存活率影響，並進一步觀察樟芝萃取物多醣及其奈米顆粒對誘導肝癌細胞（Hep G2）走向細胞凋亡的路徑。利用幾丁聚醣與氧化矽包覆樟芝萃取物多醣奈米顆粒在溶液中的粒徑為210 ± 13.3 nm，而氧化矽包覆樟芝萃取物多醣奈米顆粒在溶液中的粒徑為 294 ± 25.7 nm ，而其包覆率分別為85.7％和76.4％。以掃瞄式電子顯微鏡觀察奈米顆粒外型皆為近似球形。樟芝萃取物多醣具有很好的清除DPPH自由基的能力，而其清除超氧陰離子能力為53.3％，熬合亞鐵離子能力為50％。在奈米顆粒方面，其抗氧化能力隨溶解時間的增加而增加。對細胞存活率影響方面，不管是樟芝萃取物多醣還是奈米顆粒皆隨濃度的增加而降低各種腫瘤細胞的存活率，但是對於正常細胞則無毒性發生。進一步觀察樟芝萃取物多醣及其奈米顆粒對誘導肝癌細胞（Hep G2）走向細胞凋亡的路徑。發現不管是樟芝萃取物多醣還是奈米顆粒同樣隨濃度的增加而降低肝癌細胞（Hep G2）的存活率，此外也明顯增加sub-GI期、降低細胞內ROS的含量和粒腺體膜電位、增加Fas/APO-1、caspase-3、caspase-8和caspase-9的表現量。這些結果表示利用幾丁聚醣和氧化矽包覆樟芝萃取物多醣形成奈米顆粒對於惡性腫瘤細胞具有不錯的致死效果。

Abstract
Nanomaterials have found increasing applications in various industries. In recent years, we have witnessed many achievements originated from the research and development of biomedical nanomaterials in Taiwan. However, little information is available regarding the applications of silica and chitosan nanomaterials on the encapsulated of food ingredients.
Silicate was polymerized in the presence of chitosan to form novel silica-chitosan nanoparticles in weakly acidic solution under ambient condition. Both the turbidity of silica solution and the average hydrodynamic diameter of silica nanoparticles increased dramatically after the addition of chitosan. The initial stage of silica formation closely observed the fourth order kinetics. The latter transformation of colloidal nanoparticles approximated the exponential growth pattern during slow aggregation. Chitosan did not significantly change the rate of silica synthesis, but it facilitated the composite nanoparticles to aggregate one order of magnitude faster than pure silica nanoparticles. Scanning electron microscopy revealed that the composite nanoparticles grew in three dimensions and became clusters and aggregates within a shorter time. Atomic force microscopy demonstrated that the composite nanoparticles increased from as small as 1 nm to 32 nm after a reaction time of 1 hr and 24 hr respectively. X-ray diffraction, infrared spectroscopy and elemental analysis confirmed that these nanoparticles were amorphous composite of silica and chitosan. Synthesis of silica with chitosan provided a facile way of preparing composite silica nanoparticles with improved functional properties.
Amorphous silica is increasingly used in diagnostic and biomedical research because of their ease of production and relatively low cost. It is generally presumed to be safe because it have been approved to be used as a food or animal feed ingredient. Recent literature reveals that amorphous silica may present toxicity concern at high doses. In anticipation of increasing human exposure to silica in the future, we believe it is prudent to examine its toxicity to cells of different origins and devise novel ways to address the issue. Consequently, we investigated the response of several normal fibroblast and tumor cells at low to high doses of amorphous silica or composite nanoparticles of silica and chitosan. Cell proliferation assay indicates that pure silica nanoparticles are nontoxic at low dosages, but a decrease in cell viability appears at high dosages. Lactate dehydrogenase (LDH) assay indicates that high dosages of silica induce cell membrane damage. Both the cell proliferation and LDH assays reveal that fibroblast cells are more susceptible to injury induced by silica exposure than tumor cells. In addition, silica-chitosan composite nanoparticles induce much less adverse effect to normal cell functions. This study suggests that high concentrations of silica may become toxic to human cells, but its cytotoxicity could be significantly reduced by modifying silica with chitosan.
Antrodia camphorata fungus is a rare, expensive and popular herbal medicine in Taiwan. It has been used for the treatment of a variety of disease, such as food and drug intoxication, diarrhea, abdominal pain, hypertension, itchy skin and liver cancer. Chitosan molecules complex with silica and encapsulate the Antrodia camphorata extract (ACE) polysaccharides to form composite nanoparticles. The nanoparticle suspensions of ACE polysaccharides encapsulated in silica-chitosan or silica approach an average particle size of 210 ± 13.3 nm and 294 ± 25.7 nm in solution. The encapsulation efficiencies of ACE polysaccharides are 85.6% and 76.4%, respectively. ACE polysaccharides solution had better antioxidative capability than chitosan-silica-ACE polysaccharides and silica-ACE polysaccharides nanoparticles suspensions. The antioxidant capacity of nanoparticles increases with increasing dissolution time. The antitumor effects of ACE polysaccharides and their nanoparticles are dose dependent and they increased with increasing concentration. Encapsulation in silica nanoparticles increases the antiproliferative effects of ACE polysaccharides on four heptocellular and one lung carcinoma cells. Moreover, encapsulation in silica-chitosan nanoparticles improves the antiproliferative effects of ACE polysaccharides on ten different tumor cell lines. Encapsulation in silica-chitosan nanoparticles may provide a highly effective carrier of antitumor nutraceuticals for cancer chemoprevention.
Treatment with ACE polysaccharides, ACE polysaccharides encapsulated in silica or silica-chitosan nanoparticles decreased the cell growth of Hep G2, significantly increased the sub-GI phase population to 10%, reduced ROS generation, decreased mitochondrial membrane potential content, induced the Fas/APO-1 expression, and increased the caspase-3, caspase-8 and caspase-9 proteolytic activities. These results suggest that the encapsulation of ACE polysaccharides by chitosan and silica into composite nanoparticles affects its cytotoxicity and specificity towards cultured liver tumor cells.

Contents

Abstract (in Chinese) IV
Abstract (in English) VII
Contents XI
Introduction 1
Chapter 1: Literature reviews 5
1. Nanocomposites 5
2. Silica 7
2.1. Preparation of silica nanoparticles 8
2.2. Application of silica nanocomposites 12
3. Chitosan 13
3.1. Application of chitosan nanoparticles 13
4. Antrodia camphorata 15
4.1. Biologically active ingredients of the A. camphorata 17
4.2. Bioactive and physiological effects of the A. camphorata 19
4.2.1. Antitumor effect 19
4.2.2. Hepatoprotective effect 20
4.2.3. Antioxidant effect 20
4.2.4. Vascular effect 22

Chapter 2: Chitosan catalyzed aggregation during the biomimetic synthesis of silica nanoparticles 24
Abstract 24
1. Introduction 26
2. Materials and methods 28
2.1. Preparation of silica nanoparticles 29
2.2. Analytical 30
3. Results and discussion 31
3.1. Kinetics of silica synthesis 31
3.2. Effect of chitosan on silica synthesis 33
3.3. Change in the turbidity of solution 34
3.4. Kinetics of nanoparticle aggregation 35
3.5. Size evolution of silica nanoparticles 37
3.6. Structural characteristics of composite nanoparticles 38
4. Conclusion 39
Chapter 3: The in vitro cytotoxicitiy of silica nanoparticles at high concentrations strongly depends on the metabolic activity type of cell line 51
Abstract 51
1. Introduction 53
2. Materials and methods 55
2.1. Reagents and chemicals 55
2.2. Nanoparticle preparation and dispersion 56
2.3. Nanoparticles characterization 57
2.4. Cell culture and exposure to nanoparticles 58
3. Results and discussion 61
3.1. Structural characteristics of composite nanoparticles 61
3.2. Cytotoxicity of silica or silica-chitosan composite nanoparticles 62
4. Conclusion 69

Chapter 4: Encapsulation by silica-chitosan nanoparticles enhances the antiproliferative effect of Antrodia camphorata polysaccharides on cultured tumor cells 76
Abstract 76
1. Introduction 78
2. Materials and methods 80
2.1. Reagents and chemicals 80
2.2. Preparation of Antrodia camphorata extract polysaccharides 81
2.3. Antrodia camphorata extract polysaccharides characterization 82
2.4. Preparation of Antrodia camphorata extract polysaccharides encapsulated in silica-chitosan or silica nanoparticles 83
2.5. Characterization of Antrodia camphorata extract polysaccharides encapsulated in silica-chitosan or silica nanoparticles 83
2.6. Antioxidant capacity 84
2.6.1 Scavenging of 1, 1-diphenyl-2-picrylhydrazyl radicals 84
2.6.2 Chelating of ferrous ions 85
2.6.3 Scavenging of superoxide anion 85
2.7. Cell culture 86
2.8. Mitochondrial activity 87
3. Results and discussion 88
3.1. Structural characteristics of ACE polysaccharides 88
3.2. Size measurement of ACE polysaccharides encapsulated in silica or silica-chitosan nanoparticles 90
3.3. Antioxidative properties of ACE polysaccharides, or ACE polysaccharides encapsulated in silica or silica-chitosan nanoparticles 90
3.4. The antitumor properties of ACE polysaccharides, or ACE polysaccharides encapsulated in silica or silica-chitosan nanoparticles 92
4. Conclusion 97

Chapter 5: Apoptosis of hepatocellular carcinoma cells induced by Antrodia camphorata polysaccharides encapsulated in silica-chitosan nanoparticles 113
Abstract 113
1. Introduction 114
2. Materials and methods 116
2.1. Reagents and chemicals 116
2.2. Preparation and characterization of ACE polysaccharides 117
2.3. Preparation and characterization of ACE polysaccharides encapsulated in silica-chitosan or silica nanoparticles 117
2.4. Cell culture 117
2.5. Mitochondrial activity 118
2.6. Lactate dehydrogenase release 118
2.7. DNA fragmentation 118
2.8. Flow cytometric analysis of cell cycle 119
2.9. ROS generation by chemiluminescence assay 120
2.10. Mitochondrial membrane potential assay 120
2.11. Assay for Fas (APO-1/CD95) 121
2.12. Assay for caspase-3, caspase-8, and caspase-9 activity 121
3. Results and discussion 122
3.1. Effects on the cell growth and viability of Hep G2 cells 122
3.2. Induction of DNA fragmentation 124
3.3. Effect on Hep G2 cell cycle 125
3.4. Effect on the ROS production of Hep G2 cells 126
3.5. Effect on the mitochondrial apoptotic pathway 127
3.6. Effect on Fas/APO-1 of Hep G2 cells 128
3.7. Effect of on the caspase activity of Hep G2 cells 129
4. Conclusion 130

Conclusions 143
References 146

References
Albrecht, H., Tschopp, J. and Jongeneel, C. V. 1994. Bcl-2 protects from oxidative damage and apoptotic cell death without interfering with activation of NF-κB by TNF. Federation of European Biochemical Societies Letters, 351: 45□48.
Ayers, M. R. and Hunt, A. J. 2001. Synthesis and properties of chitosan- silica hybrid aerogels. Journal of Non- crystalline Solids, 285: 123□127.
Banerjee, T., Mitra, S., Singh, A. K., Sharma, R. K. and Maitra, A. 2002. Preparation, characterization and biodistribution of ultrafine chitosan nanoparticles. International Journal of Pharmacyeutics, 243: 93□105.
Barbe, C., Bartlet, J., Kong, L., Finnie, K., Lin, H. Q., Larkin, M., Calleja, S., Bush, A. and Calleja, G. 2004. Silica particles: A novel drug-delivery system. Advanced Materials, 16: 1959□1966.
Benning, L. G., Phoenix, V., Yee, N. and Tobin, M. J. 2004. Molecular characterization of cyanobacterial silicification using synchrotron infrared micro-spectroscopy. Geochimica et Cosmochimica Acta, 68: 729□741.
Briehl, M. M. and Baker, A. F. 1996. Modulation of the antioxidant defense as a factor in apoptosis. Cell Death and Differentiation, 3: 63□70.
Brunner, T. J., Wick, P., Manser, P., Spohn, P., Grass, R. N., Limbach, L. K., Bruinink, A. and Stark, W. J. 2006. In vitro cytotoxicity of oxide nanoparticles: Comparison to asbestos, silica, and the effect of particle solubility. Environmental Science and Technology, 40: 4374□4381.
Buttke, T. M. and Sandstrom, P. A. 1994. Oxidative stress as a mediator of apoptosis. Immunology Today, 15: 7□10.
Calvo, P., Remunän-Lo´pez, C., Vila-Jato, J. L. and Alonso, M. J. 1997. Novel hydrophilic chitosan–polyethylene oxide nanoparticles as protein carriers. Journal of Applied Polymer Science, 63: 125□132.
Carlesso, G., Kozlov, E., Prokop, A., Unutmaz, D. and Davidson, J. M. 2005. Nanoparticulate system for efficient gene transfer into refractory cell targets. Biomacromolecules, 6: 1185□1192.
Cha, J. N., Stucky, G. D., Morse, D. E. and Deming, T. J. 2000. Biomimetic synthesis of ordered silica structures mediated by block copolypeptides. Nature, 403: 289□ 292.
Chang, K. L. B., Tsai, G., Lee, J. and Fu, W. R. 1997. Heterogeneous N-deacetylation of chitin in alkaline solution. Carbohydrate Research, 303: 327□332.
Chang, K. L. B., Tai, M. C. and Chang, F. H. 2001. Kinetics and products of the degradation of chitosan by hydrogen peroxide. Journal of Agricultural and Food Chemistry, 49: 4845□4851.
Chang, H. L., Chao, G. R., Chen, C. C. and Mau, J. L. 2001. Non-volatile taste components of Agaricus blazei, Antrodia camphorata and Cordyceps militaris mycelia. Food Chemistry, 74: 203□207.
Chang, T. T. and Chou, W. N. 1995. Antrodia cinnamomea sp. Nov. on Cinnamomum kanehirai in Taiwan. Mycological Research, 99: 756□758.
Chen, C. H., Yang, S. W. and Shen, Y. C. 1995. New steroid acids from Antrodia cinnamomea, a fungal parasite of Cinnamomum micranthum. Jouranl of Natural Products, 58: 1655□1661.
Chen, F. and Gerion, D. 2004. Fluorescent CdSe/ ZnS nanocrystal-peptide conjugates for long-term, nontoxic imaging and nuclear targeting in living cells. Nano Letters, 4: 1827□1832.
Chen, H., Weiss, J. and Shahidi, F. 2006. Nanotechnology in nutraceuticals and functional foods. Food Technology, 60: 30□36.
Chen, L. and Subirade, M. 2005. Chitosan/β-lactoglobulin core-shell nanoparticles as nutracutial carriers. Biomaterials, 26:6041□6053.
Chen, M. and von Mikecz, A. 2005. Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO2 nanoparticles. Experimental Cell Research, 305: 51□62.
Chen, X. G., Lee, C. M. and Park, H. J. 2003. O/W emulsification for the self-aggregation and nanoparticle formation of linoleic acid-modified chitosan in the aqueous system. Journal of Agricultural and Food Chemistry, 51: 3135□3139.
Chen, Y., Chen, J., Dong, J. and Jin, Y. 2004. Comparing study of the effect of nanosized silicon dioxide and microsized silicon dioxide on fibrogenesis in rats. Toxicology and Industrial Health, 20: 21□27.
Cheng, J. J., Huang, N. K., Chang, T. T., Wang, D. L. and Lu, M. K. 2005a. Study for anti-angiogenic activities of polysaccharides isolated from Antrodia cinnamomea in endothelial cells. Life Science, 76: 3029□3042.
Cheng, J. J., Yang, C. J., Cheng, C. H., Wang, Y. T., Huang, N. K. and Lu, M. K. 2005b. Characterization and functional study of Antrodia camphorata lipopolysaccharide. Journal of Agricultural and Food Chemistry. 53: 469□474.
Cherng, I. W., Wu, D. P. and Chiang, H. C. 1996. Triterpenoids from Antrodia cinnamomea. Phytochemistry, 41: 263□267.
Chiang, H. C., Wu, D. P., Cherng, I. W. and Ueng, C. H. 1995. A sesquiterpene lactone, phenyl and biphenyl compounds from Antrodia cinnamomea. Phytochemistry, 39: 613□616.
Cohen, G. M. 1997. Caspases: The executioners of apoptosis. Journal of Biochemistry, 26: 1□16.
Colvin, V. L. 2003. The potential environmental impact of engineered nanomaterials. Nature Biotechnology, 21: 1166□1170.
Coradin, T. and Livage, J. 2001. Effect of some amino acids and peptides on silicic acid polymerization. Colloids and Surfaces B: Biointerfaces, 21: 329□336.
Coradin, T. and Lopez, P. J. 2003. Biogenic silica patterning: Simple chemistry or subtle biology? ChemBioChem, 4: 251□259.
Coradin, T., Durupthy, O. and Livage, J. 2002. Interactions of amino-containing peptides with sodium silicate and colloidal silica: A biomimetic approach of silicification. Langmuir, 18: 2331□2336.
Coradin, T., Coupé, A. and Livage, J. 2003. Interactions of bovine serum albumin and lysozyme with sodium silicate solutions. Colloids and Surfaces B, 29: 189-196.
Coyle, J. T. and Puttfarcken, P. 1993. Oxidative stress, glutamate, and neurodegenerative disorders. Science, 262: 689□695.
Cui, D. and Cao, H. 2003. Advance and prospect of bionanomaterials. Biotechnology Progress, 19: 683□692.
Dai, Y. Y., Chuang, C. H., Tsai, C.C., Sio, H. M., Huang, S. C., Chen, J. C. and Hu, M. L. 2003. The protection of Antrodia camphorata against acute hepatotoxicity of alcohol in rats. Journalof Food and Drug Analysis, 11: 177□185.
Ding, L., Stilwell, J., Zhang, T., Elboudwarej, O., Jiang, H., Selegue, J. P., Cooke, P. A., Gray, J. W. and Chen, F. F. 2005. Molecular characterization of the cytotoxic mechanism of multiwall carbon nanotubes and nano-onions on human skin fibroblast. Nano Letters, 5: 2448□2464.
Dippold, W. G., Kron, G., Boosfeld, E., Dienes, H. P., Klingel, R., Knuth, A., Wanger, R. and Büschenfelde, K. H. M. Z. 1987. Signet ring stomach cancer: morphological characterization and antigenic profile of a newly established cell line (Mz-Sto-1). European Journal of Cancer Clinical Oncology, 23: 697□701
Derfus, A. 2004. Probing the cytotoxicity of semiconductor quantum dots. Nano Letters, 4: 11□18.
Donaldson, K., Aitken, R., Tran, L., Stone, V., Duffin, R., Forrest, G. and Alexander, A. 2006. Carbon nanotubes: A review of their properties in relation to pulmonary toxicology and workplace safety. Toxicological Sciences, 92: 5□22.
Fernández-Urrusuno, R., Calvo, P., Remunan-Lopez, J. L., Villa-Jato, J. L. and Alonso, M. J. 1999. Enhancement of nasal absorption of insulin using chitosan nanoparticles. Pharmacological Research, 9: 429□436.
Frank, L., Avramoglou, T., Sainte-Catherine, O., Jozefonvicz, J. and Kraemer, M. 2004. Growth inhibition of MCF-7 tumor cell line by phenylacetate linked to functionalized dextran. Journal of Biomaterials Science: Polymer Edition, 15: 1305–1315.
Garcia-Ruiz, C., Colell, A., Mari, M., Morales, A. and Fernandez-Checa, J. C. 1997. Direct effect of ceramide on the mitochondrial electron transport chain leads to generation of reactive oxygen species. Role of mitochondrial glutathione. Journal of Biological Chemistry, 272: 11369□11377.
Georganopoulou, D. G., Chang, L., Nam, J. M., Thaxton, C. S., Mufson, E. J., Klein, W. L. and Mirkin, C. A. 2005. From the cover: Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America, 102: 2273□2276.
Gill, I. 2001. Bio-doped nanocomposite polymers: Sol-gel bioencapsulates. Chemistry of Materials, 13: 3404□3421.
Gill, I. and Ballesteros, A. 2000. Bioencapsulation within synthetic polymers (part 1): Sol-gel encapsulated biologicals. TIBTECH, 18: 282□296.
Gottlieb, R. A. 2000. Role of mitochondria in apoptosis. Critical Reviews in Eukaryotic Gene Expression, 10: 231□239.
Handbook of x-ray Photoelectron Spectroscopy, Published by Perkin- Elmer Corporation Physical Electronics Division, Minnesota 55344 United States of America.
Hardman, R. A. 2006. Toxicologic review of quantum dots: Toxicity depends on physicochemical and environmental factors. Environmental Health Perspectives, 114: 165□172.
Hnizdo, E. and Vallyathan, V. 2003. Chronic obstructive pulmonary disease due to occupational exposure to silica dust: A review of epidemiological and pathological evidence. Occupational Environmental Medicine, 60: 237□243.
Hockenbery, D. M., Oltvai, Z. N., Yin, X. M., Milliman, C. L. and Korsmeyer, S. J. 1993. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell, 75: 241□251.
Hood, J. D., Bednarski, M., Frausto, R., Guccione, S., Reisfeld, R. A., Xiang, R. and Cheresh, D. A. 2002. Tumor regression by targeted gene delivery to the neovasculature. Science, 296: 2404□2407.
Hoshino, A., Fujioka, K., Oku, T., Suga, M., Sasaki, Y. and Ohta, T. 2004. Physicochemical properties and cellular toxicity of nanocrystal quantum dots depend on their surface modification. Nano Letters, 4: 2163□2169.
Hseu, Y. C., Chang, W. C., Hseu, Y. T., Lee, C. Y., Yech, Y. J., Chen, P.C., Chen, J. Y. and Yang, H. L. 2002. Protection of oxidative damage by aqueous extract from Antrodia camphorata mycelia in normal human erythrocytes. Life Sciences, 71: 469□482.
Hseu, Y. C., Yang, H. L., Lai, Y. C., Lin, J. G., Chen, G. W. and Chang, Y. H. 2004. Induction of apoptosis by Antrodia camphorata in human premyelocytic leukemia HL-60 cell. Nutrition Cancer, 48: 189□197.
Hseu, Y. C., Wu, F. Y., Wu, J. J., Chen, J. Y., Chang, W. H., Lu, F. J., Lai, Y. C. and Yang, H. L. 2005. Anti-inflammatory potential of Antrodia camphorata through inhibition of iNOS, COX-2 and cytokines via the NF-κB pathway. Interantional Immunopharmacology, 5: 1914□1925.
Hsiao, G., Shen, M. Y., Lin, K. H., Lan, M. H., Wu, L. Y., Chou, D. S., Lin, C. H., Su, C. H. and Sheu, J. R. 2003. Antioxidative and hepatoprotective effects of Antrodia camphorata extract. Journal of Agricultural and Food Chemistry, 51: 3302□3308.
Hsu, Y. L., Kuo, Y. C., Kuo, P. L., Ng, L. T., Kuo, Y. H. and Lin, C. C. 2005. Apoptotic effects of extract from Antrodia camphorata fruiting bodies in human hepatocellular carcinoma cell lines. Cancer Letters, 221: 77□89.
Hu, W. and Kavanagh, J. J. 2003. Anticancer therapy targeting the apoptotic pathway. Lancet Oncology, 4:721□729.
Huang, F., Zhang, H. and Banfield, J. F. 2003. Two-stage crystal-growth kinetics observed during hydrothermal coarsening of nanocrystalline ZnS. Nano Letters, 3: 373□378.
Huang, G. L., Liu, M. X. and Mei, X. Y. 2004. Synthesis, (1→3)-β-D-glucanase -binding ability, and phytoalexinelicitor activity of a mixture of 3, 4-epojybutyl (1→3)-β-D-oligoglucosides. Carbohydrate Research, 339: 1453□1457.
Huang, M., Khor, E. and Lim, L. T. 2004. Uptake and cytotoxicity of chitosan molecules and nanoparticles: Effects of molecular weight and degree of seacetylation. Pharmaceutical Research, 21: 344□353.
Icopini, G. A., Brantley, S. L. and Heaney, P. J. 2005. Kinetics of silica oligomerization and nanocolloid formation as a function of pH and ionic strength at 25°C. Geochimica Cosmochimica Acta, 69: 293□303.
Janes, K. A., Fresneau, M. P., Marazuela, A., Fabra, A. and Alonso, M. J. 2001. Chitosan nanoparticles as delivery systems for doxorubicin. Journal of Controlled Release, 73: 255□267.
Ji, X., Eric Hampsey, J., Hu, Q., He, J., Yang, Z. and Lu, Y. 2003. Mesoporous silica-reinforced polymer nanocomposites. Chemistry of Materials, 15: 3656□3662.
Jia, G., Wang, H., Yan, L., Wang, X., Pei, R., Yan, T., Zhao, Y. and Guo, X. 2005. Cytotoxicity of carbon nanomaterials: Single-wall nanotube, multi-wall nanotube, and fullerene. Environmental Science and Technology, 39: 1378□1383.
J. N. Bykov, V., Issaeva, N., Selivanova, G. and Wiman, K. G. 2002. Mutant p53-dependent growth suppression distinguishes PRIMA-1 from known anticancer drugs: A statistical analysis of information in the National Cancer Institute database. Carcinogenesis, 23: 2011□2018.
Kai, E. and Ochiya, T. 2004. A method for oral DNA delivery with N-acetylated chitosan. Pharmaceutical Research, 21: 838□843.
Kawashima, D., Aihara, T., Kobayashi, Y., Kyotani, T. and Tomita, A. 2000. Preparation of mesoporous carbon from organic polymer/ silica nanocomposite. Chemistry of Materials, 12: 3397□3401.
Kirchner, C., Liedl, T., Kudera, S., Pellegrino, T., Munoz Javier, A., Gaub, H. E., Stolzle, S., Fertig, N. and Parak, W. J. 2005. Cytotoxicity of colloidal CdSe and CdSe/ ZnS nanoparticles. Nano Letters, 5: 331□338.
Kneuer, C., Sameti, M., Bakowsky, U., Schiestel, T., Schirra, H., Schmidt, H. and Lehr, C. M. 2000. A nonviral DNA delivery system based on surface modified silica-nanoparticles can efficiently transfect cells in vitro. Bioconjugate Chemistry, 11: 926□932.
Knorr, D. 1984. Use of chitinous polymers in food- A challenge for food research and development. Food Technology, 38 (1): 85□97.
Kresege, C. T., Leonowicz, M. E., Roth, W. J., Vartuli, J. C. and Beck, J. S. 1992. Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism. Nature, 359: 710□713.
Kröger, N., Deutzmann, R. and Sumper, M. 1999. Polycationic peptides from diatom biosilica that direct silica nanopsphere formation. Science, 286: 1129□1132.
Kröger, N., Deutzmann, R., Bergsdorf, C. and Sumper, M. 2000. Species-specific polyamines from diatoms control silica morphology. Proceedings of the National Academy of Sciences of the United States of America, 97: 14133□14138.
Kröger, N., Lorenz, S., Brumer, E. and Sumper, M. 2002. Self-assembly of highly phosphorylated silaffins and their function in biosilica morphogenesis. Science, 298: 584□586.
Kruman, I., Bruce-Keller, A., J. Bredesen, D., Waeg, G. and Mattson, M. P. 1997. Evidence that 4-hydroxynonenal mediates oxidative stress-induced neuronal apoptosis. Journal of Neuroscience, 17: 5089□5100.
Kuo, P. L., Hsu, Y. L., Cho, C. Y., Ng, L. T., Kuo, Y. H. and Lin, C. C. 2006. Apoptotic effects of Antrodia cinnamomea fruiting bodies extract are mediated through calcium and calpain-dependent pathways in Hep 3B cells. Food and Chemical Toxicology, 44: 1316□1326.
Lal, M., Levy, L., Kim, K. S., He, G. S., Wang, X., Min, Y. H., Pakatchi, S. and Prasad, P. N. 2000. Silica nanobubbles containing an organic dye in a multilayered organic/ inorganic heterostructure with enhanced luminescence. Chemistry of Materials, 12: 2632□2639.
Langer, R. and Tirrell, D. A. 2004. Designing materials for biology and medicine. Nature, 428:487□492.
Lee, I. H., Huang, R. L., Chen, C. T., Chen, H. C., Hsu, W. C. and Lu, M. K. 2002. Antrodia camphorata polysaccharides exhibit anti-hepatitis B virus effects. FEMS Microbiology Letters, 209: 63□67.
Levy, L., Sahoo, Y., Kim, K. S., Bergey, E. J. and Prasad, P. N. 2002. Nanochemistry: Synthesis and characterization of multifunctional nanoclinics for biological applications. Chemistry of Materials, 14: 3715□3721.
Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S. M., Ahmed, M., Alnemri, E. S. and Wang, X. 1997. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell, 91: 479□489.
Lim, Y., Kim, J. H., Kim, K. A., Chang, H. S., Park, Y. M., Ahn, B. Y. and Phee, Y. G.. 1999. Silica-induced apoptosis in vitro and in vivo. Toxicology Letters, 108: 335□339.
Limbach, L. K., Li, Y., Grass, R. N., Hintermann, M. A., Muller, M., Gunther, D. and Stark, W. J. 2005. Oxide nanoparticles uptake in human lung fibroblasts: effects of particles size, agglomeration, and diffusion at low concentrations. Environmental Science and Technology, 39: 9370□9376.
Lin, H. P. and Mou, C. Y. 2002. Structural and morphological control of cationic surfactant- templated mesoporous silica. Accounts of Chemical Research, 35: 927□935.
Lin, W., Huang, Y. W., Zhou, X. D. and Ma, Y. 2006. In vitro toxicity of silica nanoparticles in human lung cancer cells. Toxicological and Applied Pharmacology, 217: 252□259.
Liu, J. J., Huang, T. S., Hsu, M. L., Chen, C. C., Lin, W. S., Lu, F. J. and Chang, W. H. 2004. Antitumor effects of the partially purified polysaccharides from Antrodia camphorata and the mechanism of its action. Toxicology and Applied Pharmacology, 201: 186□193.
Loo, D. T., Copani, A., Pike, C. J., Whittemore, E. R., Walencewicz, A. J. and Cotman, C. W. 1993. Apoptosis is induced by beta-amyloid in cultured central nervous system neurons. Proceedings of the National Academy of Sciences of the United States of America, 90: 7951□7955.
Lu, Y. H. and Hwang, D. F. 2002. Effects of toxic dinoflagellates and toxin biotransformation in bivalves. Journal of Natural Toxins, 11, 315□322.
Lu, Z. M., Tao, W. Y., Zou, X. L., Fu, H. Z. and Ao, Z. H. 2007. Protective effects of mycelia of Antrodia camphorata and Armillariella tabescens in submerged culture against ethanol-induced hepatic toxicity in rats. Journal of Ethnopharmacology, 110: 160□164.
Luo, D., Han, E., Belcheva, N. and Saltzman, W. M. 2004. A self-assembled, modular DNA delivery system mediated by silica nanoparticles. Journal of Controlled Release, 95: 333□341.
Ma, Z. S., Yeoh, H. H. and Lim, L. Y. 2002. Formulation pH modulate the interaction of insulin with chitosan nanoparticles. Journal of Pharmaceutical Science, 91: 1396□1404.
Madihally, S. V. and Matthew, H. W. T. 1999. Porous chitosan scaffolds for tussue engineering. Biomaterials, 20: 1133□1142.
Magrez, A., Kasas, S., Salicio, V., Pasquier, N., Seo, J. W., Celio, M., Catsicas, S., Schwaller, B. and Forró, L. 2006. Cellular toxicity of carbon-based nanomaterials. Nano Letters, 6: 1121□1125.
Mao, H. –Q., Roy, K., Troung-Le, V. L., Janes, K. A., Lin, K. Y., Wang, Y., August, J. T. and Leong, K. W. 2001. Chitosan-DNA nanoparticles as gene carriers: Synthesis, characterization and transfection efficiency. Journal of Controlled Release, 70: 399□421.
Martin, J. E., Wilcoxon, J. P., Schaefer, D and Odinek, J. 1990. Fast aggregation of colloidal silica. Physical Review A, 41: 4379□4391.
Martinez, E. J., Owa, T., Schreiber, S. L. and Corey, E. J. 1999. Phthalascidin, a synthetic antitumor agent with potency and mode of action comparable to exteinascidin 743. Proceedings of the National Academy of Sciences of the United States of America, 96: 3496–3501.
Matsusaki, M., Larsson, K., Akagi, T., Lindstedt, M., Akashi, M. and Borrebaeck, C. A. K. 2005. Nanosphere induced gene expression in human dendritic cells. Nano Letters, 5: 2168□2173.
Matthew, M., Hanasono, M. D., Magdalena Kita, B. S., Anthony A. Mikulec, M. D., Devon Lonergan, B. S. and R. James Koch, M. D. 2003. Autocrine growth factor production by fetal, keloid, and normal dermal fibroblasts. Archives of Facial Plastic Surgery, 5: 26–30.
Mau, J. L., Huang, P. N., Huang, S. J. and Chen, C. C. 2004. Antioxidant properties of methanolic extracts from two kinds of Antrodia camphorata mycelia. Food Chemistry, 86: 25□31.
Mcllroy, D., Sakahira, H., Talanian, R. V. and Nagata, S. 1999. Involvement of caspase 3-activated DNase in internucleosomal DNA cleavage induced by diverse apoptotic stimuli. Oncogene, 18: 401□408.
Mi, F. L., Lin, Y. M., Wu, Y. B., Shyu, S. S., and Tsai, Y. H. 2002a. Chitin/PLGA blend microspheres as a biodegradable drug-delivery system: Phase-separation, degradation and release behavior. Biomaterials, 23: 3257□3267.
Mi, F. L., Tan, Y. C., Liang, H. F. and Sung, H. W. 2002b. In vivo biocompatibility and degradability of a novel injectable chitosan-based implant. Biomaterials, 23: 181□191.
Michalet, X., Pinaud, F. F., Bentolila, L. A., Tsay, J. M., Doose, S., Li, J. J., Sundaresan, G., Wu, A. M., Gambhir, S. S. and Weiss, S. 2005. Quantum dots for live cells, in vivo imaging, and diagnostics. Science, 307: 538□544.
Mignotte, B. and Vayssiere, J. L. 1998. Mitochondria and apoptosis. European Journal of Biochemistry, 252: 1□15.
Mitchell, D. T., Lee, S. B., Trofin, L., Li, N., Nevanen, T. K., Söderlund, H. and Martin, C. R. 2002. Smart nanotubes for bioseparations and biocatalysis. Journal of the American Chemical Society, 124: 11864□11865.
Mizuno, T. 1999. The extraction and development of antitumor-active polysaccharides from medicinal mushrooms in Japan (review). Internal Journal of Medicinal Mushrooms, 1: 9□29.
Moore, M. N. 2006. Do nanoparticles present ecotoxicological risks for the health of the aquatic environment? Environment International, 32: 967□976.
Moraru, C. I., Panchapakesan, C. P., Juang, Q., Takhistov, P., Liu, S. and Kokini, J. L. 2003. Nanotechnology: A new frontier in food science. Food Technology, 57: 24□29.
Mori, H., Muller, A. H. E. and Klee, J. E. 2003. Intelligent colloidal hybrids via reversible pH-induced complexation of polyelectrolyte and silica nanoparticles. Journal of the American Chemical Society, 125: 3712□3713.
Morse, D. E. 1999. Silicon biotechnology: harnessing biological silica production to construct new materials. Trends Biotechnology, 17: 230□232.
Mosmann, T. 1983. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. Journal of Immunological Methods, 65: 55□63.
Muzzarelli, R. A. A. 1983. Chitin and its derivatives: New trends of applied research. Carbohydrate Polymer, 3: 53□75.
Muzzarelli, R. A. A. 1996. Chitosan-based dietary foods. Carbohydrate Polymer, 29: 309□316.
Muzzarelli, R. A. A. and Rocchetti, R. 1985. Determination of the degree of acetylation of chitosans by first derivative ultraviolet spectrophotometry. Carbohydrate Polymers, 5: 461□472.
Nakamura, N., Hirakawa, A., Gao, J. J., Kakuda, H., Shiro, M., Komatsu, Y., Sheu, C. C. and Hattori, M. 2004. Five new maleic and succinic acid derivatives from the mycelium of Antrodia camphorata and their cytotoxic effects on LLC tumor cell line. Journal of Natural Products, 67: 46□48.
Nel, A., Xia, T., Mädler, L. and Li, N. 2006. Toxic potential of materials at the nanolevel. Science, 311: 622□627.
Nishikimi, M., Rao, N. A. and Yagi. K. 1972. The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochemical and Biophysical Research Communications, 46: 849□843.
Nishioka, Y., Kyotani, S., Okamura, M., Miyazaki, M., Okazaki, K., Ohnishi, S., Yamamoto, Y. and Ito, K. 1990. Release characteristics of cisplatin chitosan microspheres and effects of containing chitin. Chemical Pharmaceutical Bulletin, 38: 2871□2873.
Oberdörster G., Oberdörster E. and Oberdörster J. 2005. Nanotoxicology: An emerging discipline evolving from studies of ultrafine particles. Environmental Health Perspectives, 113: 823□839.
Pan, Y., Li, Y. J., Zhao, H. Y., Zheng, J. M., Xu, H., Wei, G., Hao, J. S. and Cui, F. D. 2002. Bioadhesive polysaccharide in protein delivery system: Chitosan nanoparticles improve the intestinal absorption of insulin in vivo. International Journal of Pharmaceutics, 249: 139□147.
Pandurangi, R. S., Seehra, M. S., Razzaboni, B. L. and Bolsaitis, P. 1990. Surface and bulk infrared modes of crystalline and amorphorous silica particles: A study of the relation of surface structure to cytotoxicity of respirable silica. Environmental Health Perspectives, 86: 327□336.
Patwardhan, S. V. and Clarson, S. J. 2002. Silicification and biosilicification. part 4. Effect of template size on the formation of silica. Journal of Inorganic and Organometallic Polymers, 12: 109□112.
Peng, C. C., Chen, K. C., Peng, R. Y., Chyau, C. C., Su, C. H. and Hsieh-Li, H. M. 2007. Antrodia camphorata extract induces replicative senescence in superficial TCC and inhibits the absolute migration capability in invasive bladder carcinoma cells. Journal of Ethnopharmacology, 109: 93□103.
Perry, C. C. and Keeling-Tucker, T. J. 2000. Biosilicification: the role of the organic matrix in structure control. Journal of Biology Inorganic Chemistry, 5: 537□550.
Perry, C. C. and Keeling-Tucker, T. 2003. Model studies of colloidal silica precipitation using biosilica extracts from Equisetum telmateia. Colloids of Polymer Science, 281: 652□664.
Peters, K., Unger, R. E., Kirkpatrick, C. J., Gatti, A. M. and Monari, E. 2004. Effects of nano-scaled particles on endothelial cell function in vitro: Studies on viability, proliferation and inflammation. Journal of Materials Science: Materials in Medicine, 15: 321□325.
Promega, CytoTox 96R non-raduoactive cytotoxicity assay technical bulletin, Part# TB163, revised 9/04. Promega Corporation, Madison, WI 53711-5399 United States of America.
Radin, S., El- Bassyouni, G., Vresilovic, E. J., Schepers, E. and Ducheyne, P. 2005. In vivo tissue response to resorbable silica xerogels as controlled-release materials. Biomaterials, 26: 1043□1052.
Rashidova, S. Sh., Shakarova, D. Sh., Ruzimuradov, O. N. Satubaldieva, D. T., Zalyalieva, S. V., Shpigun, O. A., Varlamov, V. P. and Kabulov, B. D. 2004. Bionanocompositional chitosan- silica sorbent for liquid chromatography. Journal of Chromatography B, 800: 49□53.
Ravi Kumar, M. N. V. 2000a. A review of chitin and chitosan applications. Reactive and Functional Polymer, 46: 1□27.
Ravi Kumar, M. N. V. 2000b. Nano and microparticles as controlled drug delivery Devices. Journal of Pharmacy and Pharmaceutical Sciences, 3: 234□258.
Roy, K., Mao, H. Q., Huang, S. K. and Leong K. W. 1999. Oral gene delivery with chitosan-DNA nanoparticles generates immunologic protection in a murine model of peanut allergy. Nature, 5: 387□391.
Roy, I., Ohulchanskyy, T. Y., Bharali, D. J., Pudavar, H. E., Mistretta, R. A., Kaur, N. and Prasad, P. N. 2005. Optical tracking of organically modified silica nanoparticles as DNA carriers: A nonviral, nanomedicine approach for gene delivery. Proceedings of the National Academy of Sciences of the United States of America, 102: 279□284.
Sanguansri, P. and Augustin, M. A. 2006. Nanoscale materials development: A food industry perspective. Trends in Food Science and Technology, 17: 547□556.
Schins, R. P. F., Duffin, R., Höhr, D., Knaapen, Ad M., Shi, T., Weishaupt, C., Stone, V., Donaldson, K. and Borm, P. J. A. 2002. Surface modification of quartz inhibits toxicity, particle uptake, and oxidative DNA damage in human lung epithelial cells. Chemical Research in Toxicology, 15: 1166□1173.
Schottenfeld, D. and Beebe-Dimmer, J. 2006. Chronic inflammation: a common and important factor in the pathogenesis of neoplasia. CA A Cancer Journal for Clinicians, 56: 69□83.
Shchipunov, Y. A. and Karpenko, T. Y. 2004. Hybrid polysaccharide-silica nanocomposites prepared by the sol-gel technique. Langmuir, 20: 3882□3887.
Shchipunov, Y. A., Karpenko, T. Y., Bakunina, I. Y., Burtseva, Y. V. and Zvyagintseva, T. N. 2004. A new precursor for the immobilization of enzymes inside sol-gel-derived hybrid silica nanocomposites containing polysaccharides. Journal of Biochemical and Biophysical Methods, 58: 25□36.
Shchipunov, Y. A., Kojima, A. and Imae, T. 2005. Polysaccharides as a template for silicate generated by sol–gel processes. Journal of Colloid and Interface Science, 285: 574□580.
Shen, Y. C., Wang, Y. H., Chou, Y. C., Chen, C. F., Lin, L. C., Chang, T. T., Tien, J. H. and Chou, C. J. 2004a. Evaluation of the anti-inflammatory activity of zhankuic acids isolated from the fruiting bodies of Antrodia camphorata. Planta Medica, 70: 310□314.
Shen, Y. C., Chou, C. J., Wang, Y. H., Chen, C. F., Chou, Y. C. and Lu, M. K. 2004b. Anti-inflammatory activity of the extracts from mycelia of Antrodia camphorata cultured with water-soluble fractions from five different Cinnamomum species. FEMS Microbiology Letters, 231: 137□143.
Shimada, K., Fujikawa, K., Yahara, K. and Nakamura, T. 1992. Antioxidative properties of xanthan on the autoxidation of soybean oil in cyclodextrin emulsion. Journal of Agricultural and Food Chemistry, 40: 945□948.
Shimizu, K., Cha, J., Stucky, G. D. and Morse, D. E. 1998. Silicatein α: Cathepsin L-like protein in sponge biosilica. Proceedings of the National Academy of Sciences of the United States of America, 95: 6234□6238.
Siegel, R.W., Hu, E. and Roco, M. C. 1999. Nanostructure Science and Technology: A Worldwide Study. R&D Status and Trends in Nanoparticles, Nanostructured Materials, and Nanodevices 1999, WTEC, Loyola College in Maryland.
Skaug, V. and Gylseth, B. 1983. Hemolytic activities of five different calcium silicates. Environmental Health Perspectives, 51: 195□203.
Song, T. Y. and Yen, G. C. 2002. Antioxidant properties of Antrodia camphorata in submerged culture. Journal of Agricultural and Food Chemistry, 50: 3322□3327.
Song, T. Y. and Yen, G. C. 2003. Protective effects of fermented filtrate from Antrodia camphorata in submerged culture against CCl4-induced hepatic toxicity in rats. Journal of Agricultural and Food Chemistry, 51: 1571□1577.
Song, T. Y., Hsu, S. L. and Yen, G. C. 2005. Induction of apoptosis in human hepatoma cells by mycelia of Antrodia camphorata in submerged culture. Journal of Ethnopharmacology, 100: 158□167.
Sumper, M. 2002. A phase separation model for the nanopatterning of diatom biosilica. Science, 295: 2430□2433.
Suzuki, T., Mizushima, Y., Umeda, T. and Ohashi, R. 1999. Further biocompatibility testing of silica-chitosan complex membrane in the production of tissue plasminogen activator by epithelial and fibroblast cells. Journal of Bioscience and Bioengineering, 88: 194□199.
Tan, W., Wang, K., He, X., Zhao, X. J., Drake, T., Wang, L. and Bagwe, R. P. 2004. Bionanotechnology base on silica nanoparticles. Medicinal Research Reviews, 24: 621□638.
Tanaka, M. and Takahashib, K. 2001. Silicate species in high pH solution molybdate, whose silica concentration is determined by colorimetry. Analytica Chimica Acta, 429: 117□664.
Tepper, C. G., Seldin, M. F. and Mudryj, M. 2000. Fas-mediated apoptosis of proliferating, transiently growth-arrested, and senescent normal human fibroblasts. Experimental Cell Research, 260: 9□19.
Tian, D., Blacher, S. and Terome, R. 1999. Biodegradable and biocompatible inorganic-organic hybrid materials: 4. Effect of acid content and water content on the incorporation of aliphatic polyesters into silica by the sol-gel process. Polymer, 40: 951□957.
Turley, J. M., Fu, T., Ruscetti, F. W., Mikovits, J. A., Bertolette, D. C. and Birchenall-Roberts, M. C. 1997. Vitamin E succinate induces Fas-mediated apoptosis in estrogen receptor- negative human breast cancer cells. Cancer Research, 57: 881□890.
Underhill, R. S., Jovanovic, A. V., Carino, S. R., Varshney, M., Shah, D. O., Dennis, D. M., Morey,□ T. E. and Duran, R. S. 2002. Oil-filled silica nanocapsules for lipophilic drug uptake: Implications for drug detoxification therapy. Chemistry of Materials, 14: 4919□4925
Wang, C., Zhang, Y., Dong, L., Fu, L., Bai, Y., Li, T., Xu, J. and Wei, Y. 2000. Two-dimensional ordered arrays of silica nanoparticles. Chemistry of Materials, 12: 3662□3666.
Wang, G. J., Tseng, H. W., Chou, C. J., Tsai, T. H., Chen, C. T. and Lu, M. K. 2003. The vasorelaxation of Antrodia camphorata mycelia: Involvement of endothelial Ca(2+)-NO-cGMP pathway. Life Science, 73: 2769□2783.
Wang, L. and Tan, W. 2006. Multicolor FRET silica nanoparticles by single wavelength excitation. Nano Letters, 6: 84□88.
Wang, L., Wang, L., Xia, T., Bian, G., Dong, L., Tang, Z. and Wang, F. 2005. A highly sensitive assay for spectrofluorimetric determination of reduced glutathione using organic nano-probes. Spectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy, 61: 2533□2538.
Wang, L., Yang, C. and Tan, W. 2005. Dual-luminophore-doped silica nanoparticles for multiplexed signaling. Nano Letters, 5: 37□43.
Wang, L., Wang, K., Santra, S., Zhao, X., Hilliard, L. R., Smith, J. E., Wu, Y. and Tan, W. 2006. Watching silica nanoparticles glow in the biological world. Analysis of Chemistry, 78: 646□654.
Warheit, D. B., Laurence, B. R., Reed, K. L., Roach, D. H., Reynolds, G. A. and Webb, T. R. 2004. Comparative pulmonary toxicity assessment of single-wall carbon nanotubes in rats. Toxicological Science, 77: 117□125.
Wei, Y., Xu, J., Dong, H., Cong, J. H., Qiu, K. and Jansen-Varnum, S. A. 1999. Preparation and physisorption characterization of D-glucose-templated mesoparous silica sol-gel materials. Chemistry of Materials, 11: 2023□2029.
Wu, S. H., Ryvarden, L. and Chang, T. T. 1997. Antrodia camphorata (`niu-chang-chih'), new combination of a medicinal fungus in Taiwan. Botanical Bulletin of Academia Sinica, 38: 273□275.
Wyllie, A. H. 1980. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature, 284: 555□556.
Xia, T., Kovochich, M., Brant, J., Hotze, M., Sempf, J., Oberley, T., Sioutas, C., Yeh, J. I., Wiesner, M. R. and Nel, A. E. 2006. Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. Nano Letters, 6: 1794□1807.
Xu, Y. and Du, Y. 2003. Effect of molecular structure of chitosan: Protein delivery properties of chitosan nanoparticles. International Journal of Pharmacyeutics, 250: 215□226.
Yang, S. W., Shen, Y. C. and Chen, C. H. 1996. Steroids and triterpenoids of Antrodia cinnamomea- A fungus parasitic on Cinnamomum micranthum. Phytochemistry, 41: 1389□1392.
Yang, W., Zhang, C. G., Qu, H. Y., Yang, H. H. and Xu, J. G. 2004. Novel fluorescent silica nanoparticle probe for ultrasensitive immunoassays. Analytica Chimica Acta, 503: 163□169.
Yang, H. L., Chen, C. S., Chang, W. H., Lu, F. J., Lai, Y. C., Chen, C. C., Hseu, T. H., Kuo, C. T. and Hseu, Y. C. 2006. Growth inhibition and induction of apoptosis in MCF-7 breast cancer cells by Antrodia camphorata. Cancer Letters, 231: 215□227.
Zang, M. and Su, C. H. 1990. Ganoderma comphoratum, a new taxon in genus Ganoderma from Taiwan, China. Acta Botanical Yannanical, 13: 395□396.
Zaremba, C. and Stuckyt, G. D. 1996. Biosilicates and biomimetic silicate synthesis. Current Opinion in Solid State and Materials Science, 1: 425□429.
Zhang, H., Oh, M., Allen, C. and Kumacheva, E. 2004. Monodisperse chitosan nanoparticles for mucosal drug delivery. Biomacromolecules, 5: 2461□2468.
Zhang, T., Stilwell, J. L., Gerion, D., Ding, L., Elboudwarej, O., Cooke, P. A., Gray, J. W., Alivisatos, A. P. and Chen, F. F. 2006. Cellular effect of high doses of silica-coated quantum dot profiled with high throughput gene expression analysis and high content cellomics measurements. Nano Letters, 6: 800□808.
Zhao, X., Hilliard, L., Mechery, S., Wang, Y., Bagwe, R., Jin, S. and Tan, W. 2004. A rapid bioassay for single bacterial cell quantitation using bioconjugated nanoparticles. Proceedings of the National Academy of Sciences of the United States of America, 101: 15027□15032.
Zhong, J., Wen, W. Y. and Jones, A. A. 2003. Enhancement of diffusion in a high-permeability polymer by the addition of nanoparticles. Macromolecules, 36: 6430□6432.
Zhu, S. G., Xiang, J. J., Li, X. L., Shen, S. R., Lu, H. B., Zhou, J., Xiong, W., Zhang, B. C., Nie, X. M., Zhou, M., Tang, K. and Li, G. Y. 2004. Poly (L-lysine)-modified silica nanoparticles for the delivery of antisense oligonucleotides. Biotechnology and Applied Biochemisty, 39: 179□187.
Zong, W. X. and Thompson, C. B. 2006. A toxicologic review of quantum dots: Toxicity depends on physicochemical and environmental factors. Genes and Development, 20: 1□15.
Zou, C., Liebert, M., Zou, C., Grossman, H. B. and Lotan, R. 2001. Identification of effective retinoids for inhibiting growth and inducing apoptosis in bladder cancer cells. Journal of Urology, 165: 986□992.