上轉換奈米材料特性為吸收長波長光源轉換成短波長的螢光，為本研究主要應用。選用上轉換奈米材料為NaYF4:Yb, Tm，在材料表面包覆一層具有胺基的二氧化矽，經由3-(2-吡啶基二硫代)丙酸N-羥基琥珀醯亞胺酯(SPDP,3-(2-Pyridyldithio)propionic acid N-hydroxysuccinimide ester) 和聚乙二醇(PEG,O,O′-Bis[2-(succinylamino)ethyl]polyethylene glycol)為架橋將具有標定作用的葉酸和抗癌藥艾黴素(doxorubicin, DOX)修飾在材料上，葉酸進一步接上2-硝基苯甲基胺鹽酸鹽(photocage, 2-nitrobenzylamine hydrochloride)進行光誘導應用。NaYF4:Yb, Tm吸收980 nm 光源會釋放360 nm UV螢光，在葉酸上的photocage經由螢光共振能量轉移吸收360 nm UV螢光後，進行光斷鍵，使葉酸再度外露，與細胞膜上有葉酸過度表現的癌細胞進行接受物質媒介之內吞作用，達標定效用。當材料進入癌細胞內後，以S-S 雙硫鍵接在表面的DOX 進行釋放，達到毒殺癌細胞效用。標定效用上以葉酸過度表現和非過度表現的癌細胞進行對照測試，再選用葉酸過度表現的癌細胞進行細胞藥物毒性測試，實驗結果顯示修飾上葉酸及葉酸接上photocage 的材料接受980 nm 雷射照射進行光斷鍵後皆對葉酸過度表現的癌細胞皆有標定效用，且材料進入癌細胞後，在表面的藥物DOX 釋放達到毒殺癌細胞的效用。上轉換材料選用的激發光源為對生物體穿透度高的紅外光，利用光誘導方式達到時間及空間上的控制，應用在生物醫學的標定及藥物釋放上具有發展的潛力。

Our research bases on the property of UCNPs (Upconversion nanoparticles) which absorb long-wavelength light and convert it to short-wavelength fluorescence. NaYF4：Yb, Tm UCNPs were coated with a thin layer of SiO2, which were further modified with amino groups. After surface functionalization, the targeting ability of folic acid and the anticancer drug DOX were covalently linked to the UCNPs via PEG (O,O′-bis[2-(succinylamino)ethyl]polyethylene glycol) and SPDP (3-(2-pyridyldithio)propionic acid N-hydroxysuccinimide ester), and folic acid further connected to the photocage (2-nitrobenzylamine hydrochloride) for light-induced application. NaYF4: Yb, Tm absorbed 980nm light source then released the 360nm UV fluorescence, so that the photocage on the folic acid absorbed the 360nm UV fluorescence via fluorescence resonance energy transfer then actived the photocleavage reaction. After photocleavage, the folic acid re-exposed and particles entered the folate receptor overexpression cancer cells via substance receptor-mediated endocytosis to target cancer cells. When particles entered cancer cells, S-S disulfide bonds connected to the surface of DOX released and poisoned the cancer cells. To demonstrate the specificity of folate-mediated targeting, we chose the folate receptor positive cancer cells and folate receptor negative cancer cells to test, then chose the folate receptor positive cancer cells for toxicity test. The results showed that particles modified with folic acid and folic acid connected to the photocage which was irradiated with 980 nm laser were targeted on folate receptor positive cancer cells. When they delivered to cancer cells, the drug DOX released and achieved the efficacy of cytotoxic cancer cells.
UCNPs were irradiated with near-infrared (NIR) light to enable deep tissue- penetration depths, and by light induced it can control on time and space. If it can be applied on biomedical targeting and drug release, it will have developmental potential.

1. Freitas, R. A., Jr., What is nanomedicine? Nanomedicine : nanotechnology, biology, and medicine 2005, 1 (1), 2-9.
2. Sudeep, P. K.; Joseph, S. T. S.; Thomas, K. G., Selective detection of cysteine and glutathione using gold nanorods. J. Am. Chem. Soc. 2005, 127 (18), 6516-6517.
3. Lin, Y. S.; Wu, S. H.; Hung, Y.; Chou, Y. H.; Chang, C.; Lin, M. L.; Tsai, C. P.; Mou, C. Y., Multifunctional composite nanoparticles: Magnetic, luminescent, and mesoporous. Chem. Mater. 2006, 18 (22), 5170-5172.
4. 張芳瑜, 磁共振造影及光熱治療之雙功能複合材料的制備與探討. 國立成功大學化學研究所 2008.
5. Cheng, F. Y.; Wang, S. P.; Su, C. H.; Tsai, T. L.; Wu, P. C.; Shieh, D. B.; Chen, J. H.; Hsieh, P. C.; Yeh, C. S., Stabilizer-free poly(lactide-co-glycolide) nanoparticles for multimodal biomedical probes. Biomaterials 2008, 29 (13), 2104-2112.
6. Medintz, I. L.; Uyeda, H. T.; Goldman, E. R.; Mattoussi, H., Quantum dot bioconjugates for imaging, labelling and sensing. Nat. Mater. 2005, 4 (6), 435-446.
7. Tokumasu, F.; Fairhurst, R. M.; Ostera, G. R.; Brittain, N. J.; Hwang, J.; Wellems, T. E.; Dvorak, J. A., Band 3 modifications in Plasmodium falciparum-infected AA and CC erythrocytes assayed by autocorrelation analysis using quantum dots. J. Cell Sci 2005, 118 (5), 1091-1098.
8. Michalet, X.; Pinaud, F. F.; Bentolila, L. A.; Tsay, J. M.; Doose, S.; Li, J. J.; Sundaresan, G.; Wu, A. M.; Gambhir, S. S.; Weiss, S., Quantum dots for live cells, in vivo imaging, and diagnostics. Science 2005, 307 (5709), 538-544.
9. Winter, J. O.; Liu, T. Y.; Korgel, B. A.; Schmidt, C. E., Recognition molecule directed interfacing between semiconductor quantum dots and nerve cells. Adv. Mater. 2001, 13 (22), 1673-1677.
10. Dahan, M.; Levi, S.; Luccardini, C.; Rostaing, P.; Riveau, B.; Triller, A., Diffusion dynamics of glycine receptors revealed by single-quantum dot tracking. Science 2003, 302 (5644), 442-445.
11. Empedocles, S. A.; Norris, D. J.; Bawendi, M. G., Photoluminescence spectroscopy of single CdSe nanocrystallite quantum dots. Phys. Rev. Lett. 1996, 77 (18), 3873-3876.
12. Lidke, D. S.; Nagy, P.; Heintzmann, R.; Arndt-Jovin, D. J.; Post, J. N.; Grecco, H. E.; Jares-Erijman, E. A.; Jovin, T. M., Quantum dot ligands provide new insights into erbB/HER receptor-mediated signal transduction. Nat. Biotechnol. 2004, 22 (2), 198-203.
13. Derfus, A. M.; Chan, W. C. W.; Bhatia, S. N., Probing the cytotoxicity of semiconductor quantum dots. Nano. Lett. 2004, 4 (1), 11-18.
14. Geszke, M.; Murias, M.; Balan, L.; Medjandi, G.; Korczynski, J.; Moritz, M.; Lulek, J.; Schneider, R., Folic acid-conjugated core/shell ZnS:Mn/ZnS quantum dots as targeted probes for two photon fluorescence imaging of cancer cells. Acta Biomater. 2011, 7 (3), 1327-1338.
15. suriamoorthy, P. Z., X.; Hao, G.; Joly, A. G.; Singh, S.; Hossu, M.; Sun, X.; Chen, W., Folic acid-CdTe quantum dot cnjugates and their applications for cancer cell targeting. Cancer Nano 2010, 1,19-28.
16. Peer, D.; Karp, J. M.; Hong, S.; Farokhzad, O. C.; Margalit, R.; Langer, R., Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol. 2007, 2 (12), 751-60.
17. Meng, F.; Zhong, Z.; Feijen, J., Stimuli-responsive polymersomes for programmed drug delivery. Biomacromolecules 2009, 10 (2), 197-209.
18. Zhu, Y.; Ikoma, T.; Hanagata, N.; Kaskel, S., Rattle-type Fe3O4@SiO2 hollow mesoporous spheres as carriers for drug delivery. Small 2010, 6 (3), 471-478.
19. Popplewell, J. F.; King, S. J.; Day, J. P.; Ackrill, P.; Fifield, L. K.; Cresswell, R. G.; di Tada, M. L.; Liu, K., Kinetics of uptake and elimination of silicic acid by a human subject: a novel application of 32Si and accelerator mass spectrometry. J. Inorg. Biochem. 1998, 69 (3), 177-180.
20. Li, M. H.; Keller, P., Stimuli-responsive polymer vesicles. Soft. Matter. 2009, 5 (5), 927-937.
21. Rijcken, C. J.; Soga, O.; Hennink, W. E.; van Nostrum, C. F., Triggered destabilisation of polymeric micelles and vesicles by changing polymers polarity: an attractive tool for drug delivery. J. Control. Release 2007, 120 (3), 131-148.
22. Lai, C. Y.; Trewyn, B. G.; Jeftinija, D. M.; Jeftinija, K.; Xu, S.; Jeftinija, S.; Lin, V. S. Y., A mesoporous silica nanosphere-based carrier system with chemically removable CdS nanoparticle caps for stimuli-responsive controlled release of neurotransmitters and drug molecules. J. Am. Chem. Soc. 2003, 125 (15), 4451-4459.
23. Auzel, F., Upconversion and anti-Stokes processes with f and d ions in solids. Chem. Rev. 2004, 104 (1), 139-173.
24. Scheps, R., Upconversion laser processes. Prog. Quant. Electron. 1996, 20 (4), 271-358.
25. Armstrong, J. A. B., N.; Ducuing, J.; Pershan, P. S., Interactions between light waves in a nonlinear dielectric Physical Review 1962, 127, 1918-1939.
26. Dalton, L. R.; Harper, A. W.; Ghosn, R.; Steier, W. H.; Ziari, M.; Fetterman, H.; Shi, Y.; Mustacich, R. V.; Jen, A. K. Y.; Shea, K. J., Synthesis and processing of improved organic 2nd-order nonlinear-optical materials for applications in photonics. Chem. Mater. 1995, 7 (6), 1060-1081.
27. Zipfel, W. R.; Williams, R. M.; Christie, R.; Nikitin, A. Y.; Hyman, B. T.; Webb, W. W., Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation. P Natl Acad Sci USA 2003, 100 (12), 7075-7080.
28. Chang, E.; Thekkek, N.; Yu, W. W.; Colvin, V. L.; Drezek, R., Evaluation of quantum dot cytotoxicity based on intracellular uptake. Small 2006, 2 (12), 1412-1417.
29. Wang, F.; Liu, X. G., Recent advances in the chemistry of lanthanide-doped upconversion nanocrystals. Chem. Soc. Rev. 2009, 38 (4), 976-989.
30. Menyuk, N.; Pierce, J. W.; Dwight, K., NaYF4:Yb,Er - efficient upconversion phosphor. Appl. Phys. Lett. 1972, 21 (4), 159-161.
31. Gudel, H. U., Topics in current chemistry Springer 2001.
32. Gamelin, D. R.; Gudel, H. U., Design of luminescent inorganic materials: New photophysical processes studied by optical spectroscopy. Accounts. Chem. Res. 2000, 33 (4), 235-242.
33. Wang, X.; Li, Y. D., Monodisperse nanocrystals: general synthesis, assembly, and their applications. Chem. Commun. 2007, (28), 2901-2910.
34. Joubert, M. F., Photon avalanche upconversion in rare earth laser materials. Opt. Mater. 1999, 11 (2-3), 181-203.
35. N., B., Solid state infrared quantum counters. Phys. Rev. Lett. 1959, 2 (3), 84-85.
36. Auzel, F. E., Materials and devices using double-pumped phosphors with energy-transfer. P Ieee 1973, 61 (6), 758-786.
37. Chivian, J. S.; Case, W. E.; Eden, D. D., Photon avalanche-new phenomenon in Pr3+ based infrared quantum counters. Appl. Phys. Lett. 1979, 35 (2), 124-125.
38. Wang, M.; Abbineni, G.; Clevenger, A.; Mao, C. B.; Xu, S. K., Upconversion nanoparticles: synthesis, surface modification and biological applications. Nanomedicine 2011, 7 (6), 710-729.
39. Diamente, P. R.; Raudsepp, M.; van Veggel, F. C. J. M., Dispersible Tm3+ doped nanoparticles that exhibit strong 1.47 mu m photoluminescence. Adv. Funct. Mater. 2007, 17 (3), 363-368.
40. Xu, Z. H.; Li, C. X.; Yang, P. P.; Zhang, C. M.; Huang, S. S.; Lin, J., Rare earth fluorides nanowires/nanorods derived from hydroxides: Hydrothermal synthesis and luminescence properties. Cryst. Growth. Des. 2009, 9 (11), 4752-4758.
41. Ruoxue Yan, Y. L., Down/up conversion in Ln3+-doped YF3 nanocrystals. Adv. Funct. Mater. 2005, 15 (5), 763-770.
42. Heer, S.; Kompe, K.; Gudel, H. U.; Haase, M., Highly efficient multicolour upconversion emission in transparent colloids of lanthanide-doped NaYF4 nanocrystals. Adv. Mater. 2004, 16 (23-24), 2102-2105.
43. Wang, F.; Liu, X. G., Upconversion multicolor fine-tuning: Visible to near-infrared emission from lanthanide-doped NaYF4 nanoparticles. J. Am. Chem. Soc. 2008, 130 (17), 5642-5643.
44. Li, Z. Q.; Zhang, Y., Monodisperse silica-coated polyvinylpyrrolidone/NaYF4 nanocrystals with multicolor upconversion fluorescence emission. Angew. Chem. Int. Edit. 2006, 45 (46), 7732-7735.
45. Yi, G. S.; Lu, H. C.; Zhao, S. Y.; Yue, G.; Yang, W. J.; Chen, D. P.; Guo, L. H., Synthesis, characterization, and biological application of size-controlled nanocrystalline NaYF4 : Yb,Er infrared-to-visible up-conversion phosphors. Nano. Lett. 2004, 4 (11), 2191-2196.
46. Zijlmans, H. J. M. A. A.; Bonnet, J.; Burton, J.; Kardos, K.; Vail, T.; Niedbala, R. S.; Tanke, H. J., Detection of cell and tissue surface antigens using up-converting phosphors: A new reporter technology. Anal. Biochem 1999, 267 (1), 30-36.
47. Vetrone, F.; Mahalingam, V.; Capobianco, J. A., Near-infrared-to-blue upconversion in colloidal BaYF5:Tm3+, Yb3+ nanocrystals. Chem. Mater. 2009, 21 (9), 1847-1851.
48. Page, R. H.; Schaffers, K. I.; Waide, P. A.; Tassano, J. B.; Payne, S. A.; Krupke, W. F.; Bischel, W. K., Upconversion-pumped luminescence efficiency of rare-earth-doped hosts sensitized with trivalent ytterbium. J. Opt. Soc. Am. B 1998, 15 (3), 996-1008.
49. Thoma, R. E.; Insley, H.; Hebert, G. M., Sodium fluoride-lanthanide trifluoride systems. Inorg. Chem. 1966, 5 (7), 1222-1229.
50. Wang, F.; Han, Y.; Lim, C. S.; Lu, Y. H.; Wang, J.; Xu, J.; Chen, H. Y.; Zhang, C.; Hong, M. H.; Liu, X. G., Simultaneous phase and size control of upconversion nanocrystals through lanthanide doping. Nature 2010, 463 (7284), 1061-1065.
51. Mai, H. X.; Zhang, Y. W.; Si, R.; Yan, Z. G.; Sun, L. D.; You, L. P.; Yan, C. H., High-quality sodium rare-earth fluoride nanocrystals: Controlled synthesis and optical properties. J. Am. Chem. Soc. 2006, 128 (19), 6426-6436.
52. Kramer, K. W.; Biner, D.; Frei, G.; Gudel, H. U.; Hehlen, M. P.; Luthi, S. R., Hexagonal sodium yttrium fluoride based green and blue emitting upconversion phosphors. Chem. Mater. 2004, 16 (7), 1244-1251.
53. Aebischer, A.; Hostettler, M.; Hauser, J.; Kramer, K.; Weber, T.; Gudel, H. U.; Buergi, H. B., Structural and spectroscopic characterization of active sites in a family of light-emitting sodium lanthanide tetrafluorides. Angew. Chem. Int. Edit. 2006, 45 (17), 2802-2806.
54. Suyver, J. F.; Grimm, J.; Kramer, K. W.; Gudel, H. U., Highly efficient near-infrared to visible up-conversion process in NaYF4 : Er3+,Yb3+. J. Lumin. 2005, 114 (1), 53-59.
55. Suyver, J. F.; Grimm, J.; van Veen, M. K.; Biner, D.; Kramer, K. W.; Gudel, H. U., Upconversion spectroscopy and properties of NaYF4 doped with Er3+, Tm3+ and/or Yb3+. J. Lumin. 2006, 117 (1), 1-12.
56. Wang, G.; Peng, Q.; Li, Y., Upconversion luminescence of monodisperse CaF2:Yb3+/Er3+ nanocrystals. J. Am. Chem. Soc. 2009, 131 (40), 14200-14201.
57. Wang, L. Y.; Li, Y. D., Controlled synthesis and luminescence of lanthanide doped NaYF4 nanocrystals. Chem. Mater. 2007, 19 (4), 727-734.
58. Boyer, J. C.; Cuccia, L. A.; Capobianco, J. A., Synthesis of colloidal upconverting NaYF4: Er3+/Yb3+ and Tm3+/Yb3+ monodisperse nanocrystals. Nano. Lett. 2007, 7 (3), 847-852.
59. Zhang, Y. W.; Sun, X.; Si, R.; You, L. P.; Yan, C. H., Single-crystalline and monodisperse LaF3 triangular nanoplates from a single-source precursor. J. Am. Chem. Soc. 2005, 127 (10), 3260-3261.
60. Boyer, J. C.; Vetrone, F.; Cuccia, L. A.; Capobianco, J. A., Synthesis of colloidal upconverting NaYF4 nanocrystals doped with Er3+, Yb3+ and Tm3+, Yb3+ via thermal decomposition of lanthanide trifluoroacetate precursors. J. Am. Chem. Soc. 2006, 128 (23), 7444-74445.
61. Mai, H. X.; Zhang, Y. W.; Sun, L. D.; Yan, C. R., Size- and phase-controlled synthesis of monodisperse NaYF4 : Yb,Er nanocrystals from a unique delayed nucleation pathway monitored with upconversion spectroscopy. J. Phys. Chem C. 2007, 111 (37), 13730-13739.
62. Wei, Y.; Lu, F. Q.; Zhang, X. R.; Chen, D. P., Synthesis of oil-dispersible hexagonal-phase and hexagonal-shaped NaYF4 : Yb,Er nanoplates. Chem. Mater. 2006, 18 (24), 5733-5737.
63. Wang, L.; Zhao, W. J.; Tan, W. H., Bioconjugated silica nanoparticles: development and applications. Nano Res. 2008, 1 (2), 99-115.
64. Li, Z. Q.; Zhang, Y.; Jiang, S., Multicolor core/shell-structured upconversion fluorescent nanoparticles. Adv. Mater. 2008, 20 (24), 4765-4769.
65. Jalil, R. A.; Zhang, Y., Biocompatibility of silica coated NaYF4 upconversion fluorescent nanocrystals. Biomaterials 2008, 29 (30), 4122-4128.
66. Yi, G. S.; Chow, G. M., Synthesis of hexagonal-phase NaYF4 : Yb,Er and NaYF4 : Yb,Tm nanocrystals with efficient up-conversion fluorescence. Adv. Funct. Mater. 2006, 16 (18), 2324-2329.
67. Chen, Z. G.; Chen, H. L.; Hu, H.; Yu, M. X.; Li, F. Y.; Zhang, Q.; Zhou, Z. G.; Yi, T.; Huang, C. H., Versatile synthesis strategy for carboxylic acid-functionalized upconverting nanophosphors as biological labels. J. Am. Chem. Soc. 2008, 130 (10), 3023-3029.
68. Chatterjee, D. K.; Rufaihah, A. J.; Zhang, Y., Upconversion fluorescence imaging of cells and small animals using lanthanide doped nanocrystals. Biomaterials 2008, 29 (7), 937-943.
69. Nyk, M.; Kumar, R.; Ohulchanskyy, T. Y.; Bergey, E. J.; Prasad, P. N., High contrast in vitro and in vivo photoluminescence bioimaging using near infrared to near infrared up-conversion in Tm3+ and Yb3+ doped fluoride nanophosphors. Nano. Lett. 2008, 8 (11), 3834-3838.
70. Wang, M.; Mi, C. C.; Wang, W. X.; Liu, C. H.; Wu, Y. F.; Xu, Z. R.; Mao, C. B.; Xu, S. K., Immunolabeling and NIR-excited fluorescent imaging of HeLa cells by using NaYF4:Yb,Er upconversion nanoparticles. ACS Nano 2009, 3 (6), 1580-1586.
71. Wang, L.; Yan, R.; Huo, Z.; Zeng, J.; Bao, J.; Wang, X.; Peng, Q.; Li, Y., Fluorescence resonant energy transfer biosensor based on upconversion-luminescent nanoparticles. Angew. Chem. Int. Ed. Engl. 2005, 44 (37), 6054-6057.
72. Deng, R.; Xie, X.; Vendrell, M.; Chang, Y. T.; Liu, X., Intracellular glutathione detection using MnO2-nanosheet-modified upconversion nanoparticles. J. Am. Chem. Soc. 2011, 133 (50), 20168-20171.
73. Qian, H. S.; Guo, H. C.; Ho, P. C.; Mahendran, R.; Zhang, Y., Mesoporous-silica-coated up-conversion fluorescent nanoparticles for photodynamic therapy. Small 2009, 5 (20), 2285-2290.
74. Wang, C.; Cheng, L. A.; Liu, Z. A., Drug delivery with upconversion nanoparticles for multi-functional targeted cancer cell imaging and therapy. Biomaterials 2011, 32 (4), 1110-1120.
75. Yan, B.; Boyer, J. C.; Branda, N. R.; Zhao, Y., Near-infrared light-triggered dissociation of block copolymer micelles using upconverting nanoparticles. J. Am. Chem. Soc. 2011, 133 (49), 19714-19717.
76. Yang, Y. M.; Shao, Q.; Deng, R. R.; Wang, C.; Teng, X.; Cheng, K.; Cheng, Z.; Huang, L.; Liu, Z.; Liu, X. G.; Xing, B. G., In Vitro and In vivo uncaging and bioluminescence imaging by using photocaged upconversion nanoparticles. Angew. Chem. Int. Edit. 2012, 51 (13), 3125-3129.
77. Casey, J. P.; Blidner, R. A.; Monroe, W. T., Caged siRNAs for spatiotemporal control of gene silencing. Mol. Pharm. 2009, 6 (3), 669-685.
78. Nayak, S.; Lee, H.; Chmielewski, J.; Lyon, L. A., Folate-mediated cell targeting and cytotoxicity using thermoresponsive microgels. J. Am. Chem. Soc. 2004, 126 (33), 10258-10259.
79. Derfus, A. M.; Chen, A. A.; Min, D. H.; Ruoslahti, E.; Bhatia, S. N., Targeted quantum dot conjugates for siRNA delivery. Bioconjugate Chem. 2007, 18 (5), 1391-1396.
80. Qian, H. S.; Zhang, Y., Synthesis of hexagonal-phase core-shell NaYF4 nanocrystals with tunable upconversion fluorescence. Langmuir 2008, 24 (21), 12123-12125.
81. Greenfield, R. S.; Kaneko, T.; Daues, A.; Edson, M. A.; Fitzgerald, K. A.; Olech, L. J.; Grattan, J. A.; Spitalny, G. L.; Braslawsky, G. R., Evaluation invitro of adriamycin immunoconjugates synthesized using an acid-sensitive hydrazone linker. Cancer Res. 1990, 50 (20), 6600-6607.
82. Wang, G. F.; Qin, W. P.; Wang, L. L.; Wei, G. D.; Zhu, P. F.; Kim, R. J., Intense ultraviolet upconversion luminescence from hexagonal NaYF4 : Yb3+/Tm3+ microcrystals. Opt. Express 2008, 16 (16), 11907-11914.
83. Zhan, Q. Q.; Qian, J.; Liang, H. J.; Somesfalean, G.; Wang, D.; He, S. L.; Zhang, Z. G.; Andersson-Engels, S., Using 915 nm laser excited Tm3+/Er3+/Ho3+-doped NaYbF4 upconversion nanoparticles for in vitro and deeper in vivo Bioimaging without overheating irradiation. ACS Nano 2011, 5 (5), 3744-3757.