在本研究中，我們發展了自模板（Self-templated）的製作方式，成功地製備出多殼層中孔洞二氧化矽奈米粒子，並探討材料的生成機制與生物醫學應用。我們發現使用有機矽烷對二氧化矽表面作修飾，能藉由殼層接殼層逐步合成法，製作雙殼層-與三殼層-中孔洞二氧化矽奈米粒子，其尺寸接近100 nm，雙殼層奈米粒子與三殼層奈米粒子的大小分別為~110 nm和~140 nm，這種多殼層二氧化矽奈米粒子可為蛋黃-蛋殼結構或是中空結構。進一步地，我們發展的自模板方式，可藉由NaOH蝕刻方式調控殼層與殼層的間距，而不改變最終奈米粒子的粒徑。由於此多殼層中孔洞結構的奈米材料的特性，如殼層-殼層的空間與多孔性殼層，可以發展為具多功能性的載體。在殼層-殼層間與具孔洞的殼層裡填充可放光的螢光分子或同時搭載具有抗癌效果的藥物，能藉由環境中pH值的改變來達到同時具生物顯影與藥物傳輸之載體。我們將DOX/FITC填充之三殼層二氧化矽奈米材料（FITC填充於第二層，DOX填充於第三層）進行體外細胞實驗，可將材料送入細胞內，並成功地將DOX抗癌藥釋放出來，最後進入細胞核內與之反應，而FITC有效地被侷限在材料內，作為螢光標的的功能。同時，雙殼層與三殼層奈米粒子可有效地被應用於動物體內與體外實驗，作為活體螢光探針。

Self-templated synthesis involving interior channel wall protection as well as outermost surface passivation was crucial to successful synthesis of multishelled mesoporous silica nanospheres. The shell-by-shell fabrication of double- and triple-walled mesoporous silica nanospheres downsized to ~100 nm. The multishelled mesoporous silica can be built as rattle-type or hollow structures with ~110 nm of double-shelled and ~140 nm of triple-shelled sizes. Notably, the shell-to-shell distance can be tuned by controlling the etching period from the self-templation processes without changing the multishelled size or interior core diameter. The multishelled mesoporous nanostructures provide a platform for the development of a multifunctional vector by the inclusion of functional species into shell-to-shell cavities and porous shells. The encapsulation of the fluorphore and drug in shell-to-shell space and mesoporous shells showed that multishelled silica spheres can be used in dual-modality for imaging and drug co-delivery vectors through the appropriate selection of pH-dependent molecules. The in vitro evaluation in triple-shelled silica indicated that an anti-cancer doxorubicin (DOX), loaded in the outer periphery space, was successfully carried and released in the cytoplasm, then entered nuclei while fluorescein FITC (primarily distributed in inner periphery space) was effectively encapsulated inside the spheres. The double- and triple-shelled nanospheres consistently provided imaging probes with visible tracking capability in vitro and in vivo.

1.G. A. P. Thé, Revista Brasileira de Ensino de Fίsica 2009, 31,2302.
2.M. A. El-Sayed, Z. L. Wang, J. Phys. Chem. B 1998, 102, 6145.
3.J. H. Fendler, Chem. Rev. 1987, 87, 877.
4.M. Yudasaka, M. Zhang, S. Iijima, Chemical Physics Letter 2000, 323, 549.
5.S. Zhu, C. H. Su, J.C. Cochrance, S. Lehoczky, I. Muntele, D. Ila, Diamond and Related Materials 2001, 10, 1190.
6.M. K. Yu, Y. Y. Jeong, J. Park, S. Park, J. W. Kim, J. J. Min, K. Kim, S. Jon, Angew. Chem. Int. Ed. 2008, 47, 5362.
7.F. Y. Cheng, Saprina P. H. Wang, C. H. Su, T. L. Tsai, P. C. Wu, D. B. Shieh, J. H. Chen, Patrick C. H. Hsieh, C. S. Yeh, Biomaterials. 2008, 29, 2104.
8.S. Santra, R. P. Bagwe, D. Dutta, J. T. Stanley, G. A. Walter, W. Tan, B. M. Moudgil, R. A. Mericle, Adv. Mater. 2005, 17, 2165.
9.Y. S. Lin, S. H. Wu, Y. Hung, Y. H. Chou, C. Chang, M. L. Lin, C. P. Tsai, C. Y. Mou, Chem. Mater. 2006, 18, 5170.
10.J. Kim, J. E. Lee, S. H. Lee, J. H. Yu, J. H. Lee, T. G. Park, T. Hyeon, Adv. Mater. 2008, 20, 478.
11.K. Kataoka, T. Matsumoto, M. Yokoyama, T. Okano, Y. Sakurai, S. Fukushima, K. Okamoto, G. S. Kwon, J.Controlled Release 2000, 64,143.
12.X. Shuai, H. Ai, N. Nasongkla, S. Kim, J. Gao, J.Controlled Release. 2004, 98, 415.
13.張芳瑜, “磁共振造影及光熱治療之雙功能複合材料的製備與探討”,國立成功大學化學研究所, 2008.
14.T. M. Allen, J. Liposome Res. 1994, 4, 1.
15.J. Kunisawa, T. Masuda, K. Katayama, T. Yoshikawa, Y. Tsutsumi, M. Akashi, J. Control. Rel. 2005, 105, 344.
16.N. Settelen, O. Roch, D. Bock, R. Rooke, S. Braun and O. Meyer, J. Control. Rel. 2004, 94, 237.
17.D. Trentin, J. Hubbell, H. Hall. J. Control. Rel. 2005, 102, 263.
18.K. Maruyama, E. Holmberg, S. J. Kennel, A. Klibanov, V. P. Torchilin, L. Huang. J. Pharm. Sci. 1990, 79, 978.
19.D. Peer, J. M. Karp, S. Hong, O. C. Farokhzad, R. Margalit, R. Langer, Nature nanotechnology 2007, 2, 751.
20.C. C. Huang, C. S. Yeh, J. Mater. Sci. Technol. 2008, 24, 667.
21.K. W. Hu, C. C. Huang, J. R. Hwu, W. C. Su, D. B. Shieh, C. S. Yeh, Chem.Eur. J. 2008, 14, 2956.
22.F. Y. Cheng, C. H. Su, P. C. Wu, C. S. Yeh, Chem. Commun. 2010, 46, 3167.
23.J. Jang, H. Yoon, Adv. Mater. 2004, 16, 799.
24.C. Y. Lai, B. G. Trewyn, D. M. Jefitinija, K. Jeftinija, S. Xu, S. Jeftinija, V. S. Lin, J. Am. Chem. Soc. 2003, 125, 4451.
25.Z. Kang, Y. Liu, C. H. A. Tsang, D. D. D. Ma, X. Fan, N.B. Wong, S.T. Lee, Adv. Mater. 2009, 21, 661.
26.D. E. Kim, F. A. Jaffer, R. Weissleder, C. H. Tung, D. Schellingerhout, Blood Flow Metab 2005, 25, 226.
27.G. Miesenbö ck, D. A. De Angelis, J. E. Rothman, Nature 1998, 394, 192.
28.T. Zhang, J. Ge, Y. Hu, Q. Zhang, S. Aloni, Y. Yin, Angew. Chem. Int. Ed. 2008, 47, 5806.
29.J. Liu, S. B. Hartono, Y. G. Jin, Z. Li, G. Q. Lu, S. Z. Qiao, J. Mater. Chem. 2010, 20, 4595.
30.L. X.Wen, Z. Z. Li, H. K. Zou, A. Q. Liu, J. F. Chen, Pest Manag Sci 2005, 61, 583.
31.W. Stöber, Afrank, E Bohn, J. Colloid Interface Sci. 1968, 26, 62.
32.H. Ogihara, S. Takenaka, I. Yamanaka, E. Tanabe, A. Genseki, K. Otsuka, Chem. Mater. 2006, 18, 996.
33.J. Zygmunt, F. Krumeich, R. Nesper, Adv. Mater. 2003, 15, 1538.
34.B. C. Satishkumar, A. Govindaraj, Erasmus M. Vogl, Lipika Basumallick, C. N. R. Rao, J. Mater. Res. 1997, 12, 604.
35.D. T. Mitchell, S. B. Lee, L. Trofin, N. Li, T. K. Nevanen, H. Soderlund, C. R. Martin, J. Am. Chem. Soc. 2002, 124, 11864.
36.R. Fan, Y. Wu, D. Li, A. Majumdar, P. Yang, J. Am. Chem. Soc. 2003, 125, 5254.
37.A. Van Blaaderen, Vrij, Langmuir 1992, 8, 2921.
38.J. Y. Ying, C. P. Mehnert, M. S. Wong, Angew. Chem. Int. Ed. 1999, 38, 56.
39.Y. S. Lin, C. P. Tsai, H. Y. Huang, C. T. Kuo, Y. Huang, D. M. Huang, Y. C. Chen, C. Y. Mou, Chem. Mater. 2005, 17, 4570.
40.D. M. Huang, Y. Huang, B. S. Ko, S. C. Hsu, W. H. Chen, C. L. Chien, C. P. Tsai, C. T. Kuo, J. C. Kang, C. S. Yang, C. Y. Mou, Y. C. Chen, FASEB J. 2005, 19, 2014.
41.F. Caruso, R. A. Caruso, H. Mohwald, Science 1998, 282, 1111.
42.C. C. Chen, Y. C. Liu, C. H. Wu, C. C. Yeh, M. T. Su, Y. C. Wu, Adv. Mater. 2005, 17, 404.
43.X. W. Lou, L. A. Archer, Z. Yang, Adv Mater 2008, 20, 3987.
44.C. H. Su, H. S. Sheu, C. Y. Lim, C. C. Huang, Y. W. Lo, Y. C. Pu, J. C. Weng, D. B. Shieh, J. H. Chen, C. S. Yeh, J. Am. Chem. Soc. 2007, 129, 2139.
45.Y. Cai, H. Pan, X. Xu, Q. Hu, L. Li, R. Tang, Chem. Mater. 2007, 19, 3081.
46.Y. Sun, B. Wiley, Z. Y. Li, Y. Xia, J. Am. Chem. Soc. 2004, 126, 9399.
47.X. W. Lou, C. M. Li, L. A. Archer, Adv. Mater. 2009, 21, 2536.
48.X. W. Lou, C. Yuan, L. A. Archer, Small 2007, 3, 261.
49.W. Zhang, Z. Chen, Z. Yang, Phys. Chem. Phys. 2009, 11, 6263.
50.F. Zeng, Z. Sun, S. Wu, X. Liu, Z. Wang, Z. Tong, Macromol Chem Phys 2002, 203, 673.
51.S. B. Brijmohan, S. Swier, R. A. Weiss, M. T. Shaw, Ind Eng Chem Res 2005, 44, 8039.
52.Y. Wang, Y. Shi, X. Xu, F. Liu, H. Yao, G. Zhai, J Hao, G. Li, Colloids and Surfaces A: Physicochem Eng Aspects 2009, 345, 71.
53.C. C. Huang, N. H. Khu, C. S Yeh, Biomaterials 2010, 31, 4073.
54.I. F. Li, C. H. Su, H. S. Sheu, H. C. Chiu, Y. W. Lo, W. T. Lin, J. H. Chen, C. S. Yeh, Adv. Funct. Mater. 2008, 18,766.
55.Q. Zhang, T. Zhang, J. Ge, Y. Yin, Nano Lett 2008, 8, 2867.
56.H. P. Lin, L. Y. Yang, C. Y. Mou, S. B. Liu, H. K. Lee, New J Chem 2000, 24, 253.
57.T. Kimura, S. Saeki, Y. Sugahara, K. Kuroda, Langmuir 1999, 15, 2794.
58.Y. H. Liu, H. P. Lin, C. Y. Mou, Langmuir 2004, 20, 3231.
59.M. Yu, J. Lin, J. Fang, Chem. Mater. 2005, 17, 1783.
60.T. G. Mayerhöfer, Z. Shen, E. Leonova, M. Edén, A. Kriltz, J Popp. Chem 2008, 181, 2442.
61.M. R. S. Fuh, L. W. Burgess, T. Hirschfeld, G.D. Christian, F. Wang, Analyst 1987, 112, 1159.
62.D. J. Adams, Curr Med Chem –Anti-Cancer Agents 2005, 5, 1.
63.C. Niemann, T. Henthorn, T Krejcie, C. Shanks, C. Enders-Klein, M. Avram, Clin Pharmaool Ther 2000, 67, 342.