本研究利用高溫熱裂解法合成出Cu2S-CIS異質結構材料，藉由玻尿酸(Hyaluronic acid, HA)表面大量的親水性羧基進行相轉換，並利用EDC/Sulfo-NHS共價交聯反應結合市售光敏劑二氫卟吩(Chlorin e6, Ce6)於HA-CIS奈米材料表面，成功地合成出多功能性奈米複合材料Ce6-HA-CIS，經由UV、PL、ICP、FTIR、Zeta potential與Hr-TEM來進行奈米材料組成、結構與光學性質之分析。除此之外，Ce6-HA-CIS奈米材料在近紅外光區域擁有優越的光吸收特性，當雷射光照射銅基材後，內部銅缺陷會引起局部表面電漿共振(Localized Surface Plasmon Resonance, LSPR) ，由此特性來判斷為Ce6-HA-CIS為光熱材料，而更進一步的利用Roper’s report[102]所提出的光熱轉換效率，計算出Ce6-HA-CIS奈米複合材料的光熱轉換效率高達32.8 %。另外，材料也同時具備光敏劑Ce6之特性，可結合光熱與光動力治療來進行雙重治療之效果，並利用腫瘤細胞上的玻尿酸受體，進行針對性的標靶化治療。
在生物醫學應用上，本實驗藉由小鼠黑色素瘤(B16F1)與人體正常細胞(HEL)進行光熱與光動力之檢測，確認當材料照射雷射進行治療時，只對腫瘤細胞造成破壞，並不會影響人體正常細胞，且經由螢光顯影之效果，清楚的辨識腫瘤細胞的位置以及拍攝不同Z軸來證明標靶化之功能，以利於後續之臨床實驗。

In this study, a heterostructure Cu2S-CIS in oil phase via high temperature pyrolysis method were synthesized. The phase transfer was carried out by using hyaluronic acid (HA) and termed as HA-CIS. Further, using EDC/Sulfo-NHS cross-linker HA-CIS was conjugated with a photosensitizer chlorin e6 (Ce6) termed as Ce6-HA-CIS to be applied for photothermal/photodynamic tumour targeted therapy. The synthesis, composition, size, shape and optical properties of the nanomaterial were characterized by using UV-visible absorption and fluorescence spectroscopy, ICP, FT-IR, zeta potential, and HR-TEM. In addition, the Ce6-HA-CIS nanomaterials have excellent light absorption properties in the near-infrared (NIR) region.
In vitro and in vivo assessments using mouse melanoma (B16F1) and zebrafish embryos respectively, reveals that Ce6-HA-CIS nanoprobes exhibit low toxicity. The photothermal conversion efficiency of Ce6-HA-CIS nanocomposites was calculated to be up to 32.8%. In vitro B16F1 photothermal and photodynamic results show efficacy of treatments of the cancer cell. The confocal scanning laser imaging shows the nonoprobes effectively internalized in the B16F1 cells. Further, the ablation of cancer cells were confirmed by Trypan blue staining. Plus, human normal cells (HEL) were used to confirm that when the materials were irradiated with lasers for treatment, only tumour cells were destroyed and the normal human cells were not affected. Through, the effect of fluorescence development clearly identify the location of tumour cells and shoot different Z-axis to prove the function of the target to facilitate the follow-up clinical trials.

[1] Y. w. Jun, J. H. Lee, J. S. Choi and J. Cheon, J. Phys. Chem. B, 2005, 109, 14795.
[2] P.D. Cozzoli, T. Pellegrino and L. Manna, Chem. Soc. Rev., 2006, 35, 1195.
[3] 陸慧,陰其俊,夏姣貞 [J].化學物理學報, 2005, 18(6), 1034.
[4] V. Schmidt, J. V. Wittemann and U. Gösele, Chem. Rev., 2010, 110, 361.
[5] L. E. Euliss, J. A. DuPont, S. Gratton and J. DeSimone, Chem. Soc. Rev., 2006, 35, 1095.
[6] T. Mokari, A. Aharoni, I. Popov and U. Banin, Angew. Chem., 2006, 118, 8169.
[7] Y. Ying, S. S. Chang, C. L. Lee and C. R. C. Wang, Phys. Chem. B, 1997, 101, 6661.
[8] N. Cordente, M. Respaud, F. Senocq, M. J. Casanove, C. Amiens and B. Chaudret, Nano Lett, 2001, 1, 565-568.
[9] V. F. Puntes, D. Zanchet, C. K. Erdonmez and A. P. Alivisatos, J. Am. Chem. Soc., 2002, 124, 12874.
[10] S. Chen, Z. Fan and D. L. Carroll, J. Phys. Chem. B, 2002, 106, 10777.
[11] H. Yu, J. Li, R. A. Loomis, P. C. Gibbons, Wang and W. E. Buhro, J. Am. Chem. Soc., 2003, 125, 16168.
[12] J. W. Grebinski, K. L. Hull, J. Zhang, T. H. Kosel and M. Kuno, Chem Mater., 2004, 16, 5260.
[13] X. Zhong, R. Xie, L. Sun, I. Lieberwirth and W. Knoll, J. Phys. Chem. B, 2005, 110, 2.
[14] D. J. Milliron, S. M. Hughes, Y. Cui, L. Manna, J. Li, L. W. Wang and A. Paul Alivisatos, Nature, 2004, 430, 190.
[15] S. M. Lee, Y. w. Jun, S. N. Cho and J. Cheon, J. Am. Chem. Soc., 2002, 124, 11244-11245.
[16] N. Zhao and L. M. Qi, Adv. Mater., 2006, 18(3), 359.
[17] L. Zheng, Y. Xu, Y. Song, C. Wu, M. Zhang and Y. Xie, Inorg. Chem., 2009, 48, 4003.
[18] Y. Shi, Y. Wang, D. Wang, B. Liu, Y. Li and L. Wei, Cryst. Growth Des., 2012, 12, 1785.
[19] M. E. Norako and R. L. Brutchey, Chem. Mater., 2010, 22, 1613.
[20] B. Koo, R. N. Patel, and B. A. Korgel, Chem. Mater., 2009, 21, 1962.
[21] R. A. Laudise, Chemical & Engineering News. Archive, 1987, 65, 30.
[22] J. C. Lin and M. Z. Yates, Langmuir, 2005, 21, 2117.
[23] J. D. Mackenzie and E. P. Bescher, Accounts Chem. Res., 2007, 40, 810.
[24] P. Zhu, J. Zhang, Z. Wu and Z. Zhang, Cryst. Growth Des., 2008, 8, 3148.
[25] T. Hyeon, Chem. Commun., 2003, 8, 927.
[26] P. D. Cozzoli, T. Pellegrino and L. Manna, Chem. Soc. Rev., 2006, 35, 1195.
[27] J. Chun and J. Lee, Eur. J. Inorg. Chem., 2010, 2010, 4251.
[28] A. Huczko, Appl. Phys. A: Mater. Sci. Process. 2000, 70, 365.
[29] L. Shi and Q. Li, CrystEngComm, 2011, 13, 7262.
[30] Z. Wang, Z. Lai, G. Chen, Adv. Mater. Res., 2012, 415-417, 1755.
[31] S. Phok, S. Rajaputra and V. P. Singh, Nanotechnology, 2007, 18, 475601.
[32] L. Juan, M. X. Liang, S. D. Lin and C. Guorong, Acta Phys. Chim. Sin., 2009, 25(12), 2445
[33] R. S. Wagner, W. Ellis, Appl. Phys. Lett., 1964, 4, 89.
[34] Q. Zhang, S. J. Liu and S. H. Yu, J. Mater. Chem., 2009, 19, 191.
[35] T. Sugimoto, Adv. Colloid Interface Sci., 1987, 28, 65.
[36] Z. Y. Tang, N. A. Kotov and M. Giersig, Science, 2002, 297(5579), 237.
[37] K. S. Cho, D. V. Talapin, W. Gaschler and C. B. Murray, J. Am. Chem. Soc., 2005, 127(19), 7140.
[38] T. Tsuruoka, S. Furukawa, Y. Takashima, K. Yoshida, S. Isoda and S. Kitagawa, Angew. Chem. Int. Ed., 2009, 48, 4739.
[39] C. J. Murphy, T. K. Sau, A. M. Gole, C. J. Orendorff, J. Gao, L. Gou, S. E. Hunyadi and T. Li, J. Phys. Chem. B, 2005, 109, 13857.
[40] S. M. Lee, Y. W. Jun, S. N. Cho and J. Cheon, J. Am. Chem. Soc., 2002, 124(38), 11244.
[41] J. Wang, Q. W. Chen, C. Zeng and B. Y. Hou, Adv. Mater., 2004, 16(2), 137.
[42] C. Cheng and D. T. Haynie, J. Appl. Phys., 2005, 87, 263112.
[43] N. R. Jana, L. Gearheart and C. J. Murphy, Langmuir, 2001, 17, 6782.
[44] Y. Xiong, J. Chen, B. Wiley, Y. Xia, S. Aloni and Y. Yin, J. Am. Chem. Soc., 2005, 127, 7332.
[45] Y. Xia, Y. Xiong, B. Lim and S. E. Skrabalak, Angew. Chem. Int. Ed., 2009, 48, 60.
[46] B. Hildebrandt, P. Wust, O. Ahlers, A. Dieing, G. Sreenivasa, T. Kerner, R. Felix and H. Riess, Crit. Rev. Oncol. Hematol., 2002, 43, 33–56
[47] J. L. Roti, Int. J. Hyperthermia, 2008, 24, 3–15
[48] R. W. Habash, R. Bansal, D. Krewski and H. T. Alhafid, Crit. Rev. Bioeng., 2006, 34, 491–542
[49] J. R. Oleson, T. V. Samulski, K. A. Leopold, S. T. Clegg, M. W. Dewhirst, R. K. Dodge and S. L. George, Int. J. Radiat. Oncol., Biol., Phys., 1993, 25, 289–297
[50] P. Chakravarty, R. Marches, N. S. Zimmerman, A. D. Swafford, P. Bajaj, I. H. Musselman, P. Pantano, R. K. Draper and E. S. Vitetta, Proc. Natl. Acad. Sci. U. S. A., 2008, 105, 8697–8702
[51] R. W. Habash, R. Bansal, D. Krewski and H. T. Alhafid, Crit. Rev. Bioeng., 2007, 35, 37–121
[52] M. Johannsen, U. Gneveckow, L. Eckelt, A. Feussner, N. Waldofner, R. Scholz, S. Deger, P. Wust, S. A. Loening and A. Jordan, Int. J. Hyperthermia, 2005, 21, 637–647
[53] J. Mendecki, E. Friedenthal, C. Botstein, R. Paglione and F. Sterzer, Int. J. Radiat. Oncol., Biol., Phys., 1980, 6, 1583–1588
[54] C. L. Garrett, D. O. Draper and K. L. Knight, Journal of Athletic Training, 2000, 35, 50–55
[55] N. A. Armar and G. C. L. Lachelin, Br. J. Obstet. Gynaecol., 1993, 100, 161–164
[56] Y. Chen, L. Wang and J. Shi, Nano Today, 2016, 11, 292-308
[57] A. Chicheł, J. Skowronek, M. Kubaszewska and M. Kanikowski, Rep. Practical Oncol. Radiother., 2007, 12, 267–275
[58] B. J. Wood and Z. Neeman, Tumor Ablation, 2005, 285-300
[59] T. Corwin, G. Lindberg, O. Traxer, M. T. Gettman, T. G. Smith, M. S. Pearle and J. A. Cadeddu, J. Urol., 2001, 166, 281–284
[60] F. Litvack, W. S. Grundfest, T. Papaioannou, F. W. Mohr, A. T. Jakubowski and J. S. Forrester, Am. J. Cardiol., 1988, 61, 81–86
[61] S. Rastegar, M. Motamedi, A. J. Welch and L. J. Hayes, IEEE Trans. Biomed. Eng., 1989, 36, 1180–1187
[62] J. R. Lepock, K.-H. Cheng, H. Al-qysi, I. Sim, C. J. Koch and J. Kruuv, Int. J. Hyperthermia, 1987, 3, 123–132
[63] A. E. Caccamo, S. Desenzani, L. Belloni, A. F. Borghetti and S. Bettuzzi, J. Cell. Physiol., 2006, 207, 208–219
[64] K. J. Henle and L. A. Dethlefsen, Cancer Res., 1978, 38, 1843–1851
[65] V. K. Pustovalov, L. G. Astafyeva and W. Fritzsche, Nano Energy, 2013, 2, 1137–1141
[66] C. Y. Kuo, T. Y. Liu, A.Hardiansyah and W. Y. Chiu, Journal of Polymer Science Part A: Polymer Chemistry, 2016, 54, 2706-2713.
[67] Y. Lee, S. L. Auh, Y. Wang, B. Burnette, Y. Wang, Y. Meng, M. Beckett, R. Sharma, R. Chin and T. Tu, Blood, 2009, 114, 589–595
[68] A. A. Lugade, J. P. Moran, S. A. Gerber, R. C. Rose, J. G. Frelinger and E. M. Lord, J. Immunol., 2005, 174, 7516–7523
[69] H. Yang, H. Maoa, Z. Wan, Biomaterials, 2013, 34 (36), 9124-9133.
[70] Z. Zha, Z. Deng, Y. Li, Nanoscale, 2013, 5 (10), 4462-4467.
[71] E. Ju, K. Dong, Z. Liu, Adv Funct Mater, 2015, 25, 1574-1580.
[72] Jaque D, Martínez Maestro L, Nanoscale, 2014, 6 , 9494-9530.
[73] Y. W. Chen, Y. L. Su, S. H. Hu and S. Y. Chen, Elsevier, 2016, 105, 190-204.
[74] G. Lv , W. Guo, W. Zhang, T. Zhang, S. Li, S. Chen, A. S. Eltahan, D. Wang, Y. Wang, J. Zhang, P. C. Wang, J. Chang, and X. J. Liang, ACS NANO, 2016, 10 (10), 9637–9645.
[75] S. Wang, A. Riedinger, H. Li, C. Fu, H. Liu, L. Li, T. Liu, L. Tan, M. J. Barthel, G. Pugliese, F. D. Donato, M. S. D’Abbusco, X. Meng, L. Manna, H. Meng, and T. Pellegrino, ACS NANO, 2015, 9 (2), 1788–1800.
[76] X. Liu, B. Li, F. Fu, K. Xu, R. Zou, Q. Wang, B. Zhang, Z. Chen, and J. Hu, Dalton Trans. 2014, 43, 11709-11715 .
[77] Q. Tian, F. Jiang, R. Zou, Q. Liu, Z. Chen, M. Zhu, S. Yang, J. Wang, J. Wang, and J. Hu, ACS NANO, 2011, 5 (12), 9761–9771.
[78] J. Mou, P. Li, C. Liu, H. Xu, L. Song, J. Wang, K. Zhang, Y. Chen, J. Shi, and H. Chen, SMALL, 2015, 11, 2275–2283.
[79] M. Zhou, J. Li, S. Liang, A. K. Sood, D. Liang, and C. Li, ACS NANO, 2015, 9 (7), 7085–7096
[80] J. Russier, L. Oudjedi, M. Piponnier, C. Bussy, M. Prato, K. Kostarelos, B. Lounis, A. Bianco, and L. Cognet, Nanoscale, 2017, 9, 4642-4645.
[81] H. K. Moon, S. H. Lee, and H.C. Choi, ACS NANO, 2009, 3 (11), 3707–3713.
[82] Z. M. Markovic, L. M. H. Trajkovic, B. M. T. Markovic, D. P. Kepić, K. M. Arsikin, S. P. Jovanović, A. C. Pantovic, M. D. Dramićanin, and V. S. Trajkovic, Biomaterials, 2011, 32, 1121-1129.
[83] E. S. Shibu, M. Hamada, N. Murase and V. Biju, Elsevier, 2013, 15, 53–72.
[84] R. L. Lipson, E. J. Baldes and J. Thorac. Elsevier, 1961, 42, 623-629.
[85] T. J. Dougherty, G. B. Grindey, R. Fiel, K. R. Weishaupt and D. G. Boyle, J. Natl. Cancer Inst. 1975, 55, 115-121.
[86] T. J. Dougherty, J. E. Kaufman, A. Goldfarb, K. R.Weishaupt and D. G. Boyle, Cancer Res. 1978, 38, 2628-2635.
[87] T. J. Dougherty, G. Lawrence, J. H. Kaufman, D. Boyle, , K. R. Weishaupt and A. Goldfarb, J. Natl. Cancer Inst. 1979, 62, 231-237.
[88] A. P. Castano, T. N. Demidova and M. R. Hamblin, Elsevier, 2004, 1, 279.
[89] I. J. Macdonald and T. J. Dougherty, J. Porphyrins Phthalocyanines, 2001, 5, 105.
[90] M. Pineiro, M. M. Pereira, S. J. Formosinho and L. G. Arnaut, J. Phys. Chem., 2002, 106, 3787
[91] R. R. Allison, G. H. Downie, R. Cuenca, X. H. Hu, C. J. Childs and C. H. Sibata, Elsevier , 2004, 1, 27.
[92] A. Ormond and H. Freeman, Materials, 2013, 6, 817.
[93] Q. Peng, J. Moan and J. M. Nesland, Ultrastruct. Pathol. 1996, 20, 109.
[94] R. Hudson, M. Carcenac, K. Smith, L. Madden, O. J. Clarke, A. Pelegrin, J. Greenman and R. W. Boyle, Br. J. Cancer, 2005, 92, 1442.
[95] J. P. Taquet, C. Frochot, V. Manneville and M. Barberi-Heyob, Curr. Med. Chem., 2007, 14, 1673.
[96] S. Wang, P. Huang, L. Nie, R. Xing, D. Liu, Z. Wang, J. Lin, S. Chen, G. Niu, G. Lu, and X. Chen, Advanced Materials, 2013, 25, 3055–3061.
[97] H. Y. Yoon, H. Koo, K. Y. Choi, S. J. Lee, K. Kim, I. C. Kwon, J. F. Leary, K. Park, S. H. Yuk, J. H. Park, and K. Choi, Biomaterials, 2012, 33, 3980–3989.
[98] S. Lal, S. E. Clare and N. J. Halas, Acc. Chem. Res. 2012, 41, 1842-1851.
[99] M. R. Choi, K. J. Stanton, J. K.Stanley, C. S. Levin, R. Bardhan, D. Akin, S. Badve, J. Sturgis, J.P. Robinson, R. Bashir, N. J. Halas and S. E. Clare, Nano Lett. 2012, 7, 3759-3765.
[100] G. Saravanakumar, K. Y. Choi, H. Y. Yoon, K. Kim, J. H. Park, I. C. Kwon and K. Park, Int. J. Pharm., 2010, 394, 154.
[101] N. Sahiner and X. Jia, Turk. J. Chem., 2008, 32, 397
[102] Q. Tian, M. Tang, Y. Sun, R. Zou, Z. Chen, M. Zhu, S. Yang, J. Wang and J. Hu, Adv. Mater., 2011, 23, 3542–3547.