螢光奈米鑽石(FND)材料近年來受到矚目，起因於該材料具有氮-空缺中心(N-V) 的結構。由於單一電荷的氮-空缺中心(NV-)經雷射光激發後所放出近紅外光譜與光強度具有高穩定性且不會有螢光閃爍與光漂白的現象產生，因此適合當成長時間生物追蹤的材料◦ 另一方面，螢光奈米鑽石存在著生物相容性與材料表面多功能修飾鍵結的能力，因此常用於環境變異的偵測，如偵測溫度、電場、磁場的變化等。
生物組織成長發展中，細胞之間的溝通有其重要性。最近發現細胞間存在細胞膜奈米管(MNTs)的結構，該結構提供細胞間溝通管道與交換傳遞物質，不同種類的細胞其細胞膜奈米管結構差異性相當大。常見的疾病，如阿玆海默症、帕金森症、HIV病毒皆存在著細胞膜奈米管結構，因而針對此結構做深入的研究將有助於運送藥物治療上述疾病的應用。
本論文使用螢光奈米鑽石的特性對細胞膜奈米管做詳盡的探討。首先利用BSA與GFP分別包覆100奈米大小的螢光奈米鑽石形成蛋白質載體，當成生物追蹤的材料，我們運用共軛焦螢光顯微鏡，追蹤這些蛋白質載體於細胞膜奈米管內的移動與速率分佈解析，並得到幾種載體運送模式，這些成果都來自於單一螢光奈米鑽石的追蹤結果。另一方面，我們研發出奈米金棒吸附螢光奈米鑽石的多功能奈米複合材料，該複合材料可測量奈米尺度的溫度變化並可提供加熱的功用，我們針對癌細胞膜與癌細胞膜奈米管的熱穩定性做深入研究，並提供局部高熱殺死癌細胞的溫度資訊,，而且此治療過程具有選擇性，不會影響正常細胞。
綜合言之，我們的成果提供利用此單一螢光奈米鑽石可了解細胞間溝通與交換傳遞物質的過程，並提供局部高熱殺死癌細胞的研究與應用。

Fluorescent nanodiamond (FND) is a novel carbon based material that has drawn much attention in recent years due to its uniquely embedded defect centers named nitrogen-vacancy
(N-V) centers. Most notable is the negatively charged nitrogen-vacancy (NV ̶ ) color center which emits a highly photostable far-red fluorescence emission. Since it does not photobleach or photoblink, it can be used to track for longer times. The FND also exhibits a very good biocompatibility and its surface can be easily functionalized through covalent or non-covalent interactions with biomolecules. The NV ̶ center has been used to sense environmental variables such as temperature and electric or magnetic fields by studying the shifts in their electronic transitions or spin transitions at electronic ground state. All these characteristics make FND a promising fluorescent probe for biological applications.
Cell-to-cell communication is essential for the development and maintenance of multicellular organisms. Recently discovered membrane nanotubes (MNTs) are capable of creating intercellular communication pathways through which transport of proteins and other cytoplasmic components occurs. These cellular connections are very heterogeneous in both structure, function, and have been found to be formed in numerous cell types. MNTs are also known to participate in pathogenesis of many diseases such as Alzheimer’s, Parkinson’s and HIV. Hence, it is important to understand the dynamics of transport along these nanotubes and to explore the potential of MNTs as drug delivery channels.
This doctoral thesis presents several applications of variously functionalized FNDs in membrane nanotubes. We applied protein functionalized FNDs as a photostable tracker, as well as a protein carrier, to illustrate the transport events in MNTs of human cells. Proteins, including bovine serum albumin and green fluorescent protein, were coated on 100-nm FNDs by physical adsorption. Then single-particle tracking of the bio-conjugates in the transient membrane connections was carried out by fluorescence microscopy. We observed different types of motions and velocity distribution of cargos that took takes place inside the MNTs. Our results demonstrate the promising applications of this novel carbon-based nanomaterial for intercellular delivery of biomolecular cargo down to the single-particle level. Further, we have studied the thermostability of both MNTs and cell membrane. We have developed gold nanorods (GNR) functionalized FNDs as a two-in-one optical nanodevice that can heat and sense the temperature simultaneously. We used all-optical method to study the nanothermometry of GNR-FNDs. We also demonstrated the photoporation on MNTs using GNR-FND nanohybrids to selectively deliver drugs to cytoplasm. Finally, we performed hyperlocalized hyperthermia on cell membrane for the treatment of cancer cell. During such a treatment, cancer cells can be killed selectively, while healthy cells remain unaffected.
Our results demonstrate promising applications of this novel carbon-based nanomaterial for intercellular delivery of biomolecular cargo down to the single-particle level and a new paradigm for hyperthermia research and application.

1. Breeding, C.M. and J.E. Shigley, The "type" classification system of diamonds and its importance in gemology. Gems & Gemology, 2009. 45(2): p. 96-111.
2. Hall, H.T., The synthesis of diamond. Journal of Chemical Education, 1961. 38: p. 484-489.
3. Hall, H.T., Synthetic Diamonds. Encyclopedia of Chemical Processing and Design, 1982. 15: p. 410-435.
4. Dolmatov, V.Y., Synthesis and post-synthesis treatment of detonation nanodiamonds. Ultrananocrystalline Diamond Synthesis, Properties, and Applications, 2006: p. 347-377.
5. Mochalin, V.N., et al., The properties and applications of nanodiamonds. Nature Nanotechnology, 2012. 7(1): p. 11-23.
6. Krueger, A., et al., Deagglomeration and functionalisation of detonation diamond. Physica Status Solidi a-Applications and Materials Science, 2007. 204(9): p. 2881-2887.
7. Schwander, M. and K. Partes, A review of diamond synthesis by CVD processes. Diamond and Related Materials, 2011. 20(9): p. 1287-1301.
8. Butler, J.E. and R.L. Woodin, Thin-film diamond growth mechanisms. Philosophical Transactions of the Royal Society of London Series a-Mathematical Physical and Engineering Sciences, 1993. 342(1664): p. 209-224.
9. Zaitsev, A.M., Optical Properties of Diamond, ed. A.M. Zaitsev. 2001: Springer.
10. Collins, A.T., In properties and growth of diamond (Ed: G.Davies) INSPEC, the Institution of Electrical Engineers, London, Ch. 3,, 1994: p. 1-437.
11. Davies, G., Charge states of the vacancy in diamond. Nature, 1977. 269(5628): p. 498-500.
12. Davies, G., et al., Vacancy-related centers in diamond. Physical Review B, 1992. 46(20): p. 13157-13170.
13. Rand, S.C., In properties and growth of diamond (Ed: G. Davies). INSPEC, the Institution of Electrical Engineers, London, Ch. 7, 1994: p. 1-437.
14. Gaebel, T., et al., Photochromism in single nitrogen-vacancy defect in diamond. Applied Physics B-Lasers and Optics, 2006. 82(2): p. 243-246.
15. Siyushev, P., et al., Low-temperature optical characterization of a near-infrared single-photon emitter in nanodiamonds. New Journal of Physics, 2009. 11.
16. Wee, T.L., et al., Two-photon excited fluorescence of nitrogen-vacancy centers in proton-irradiated type ib diamond. Journal of Physical Chemistry A, 2007. 111(38): p. 9379-9386.
17. Jelezko, F., et al., Spectroscopy of single N-V centers in diamond. Single Molecules, 2001. 2(4): p. 255-260.
18. Fu, C.C., et al., Characterization and application of single fluorescent nanodiamonds as cellular biomarkers. Proceedings of the National Academy of Sciences of the United States of America, 2007. 104(3): p. 727-732.
19. Yu, S.J., et al., Bright fluorescent nanodiamonds: No photobleaching and low cytotoxicity. Journal of the American Chemical Society, 2005. 127(50): p. 17604-17605.
20. Su, L.J., et al., Creation of high density ensembles of nitrogen-vacancy centers in nitrogen-rich type Ib nanodiamonds. Nanotechnology, 2013. 24(31).
21. Doherty, M.W., et al., The negatively charged nitrogen-vacancy centre in diamond: the electronic solution. New Journal of Physics, 2011. 13.
22. Lenef, A. and S.C. Rand, Electronic structure of the N-V center in diamond: Theory. Physical Review B, 1996. 53(20): p. 13441-13455.
23. Maze, J.R., et al., Properties of nitrogen-vacancy centers in diamond: the group theoretic approach. New Journal of Physics, 2011. 13.
24. Gali, A., T. Simon, and J.E. Lowther, An ab initio study of local vibration modes of the nitrogen-vacancy center in diamond. New Journal of Physics, 2011. 13.
25. Alkauskas, A., et al., First-principles theory of the luminescence lineshape for the triplet transition in diamond NV centres. New Journal of Physics, 2014. 16.
26. Sreenivasan, V.K.A., A.V. Zvyagin, and E.M. Goldys, Luminescent nanoparticles and their applications in the life sciences. Journal of Physics-Condensed Matter, 2013. 25(19).
27. Vaijayanthimala, V., et al., The long-term stability and biocompatibility of fluorescent nanodiamond as an in vivo contrast agent. Biomaterials, 2012. 33(31): p. 7794-7802.
28. Chang, B.-M., et al., Highly Fluorescent Nanodiamonds Protein-Functionalized for Cell Labeling and Targeting. Advanced Functional Materials, 2013. 23(46): p. 5737-5745.
29. Chang, Y.-R., et al., Mass production and dynamic imaging of fluorescent nanodiamonds. Nat Nano, 2008. 3(5): p. 284-288.
30. Wee, T.L., et al., Preparation and characterization of green fluorescent nanodiamonds for biological applications. Diamond and Related Materials, 2009. 18(2-3): p. 567-573.
31. Kuo, Y., et al., Fluorescent nanodiamond as a probe for the intercellular transport of proteins in vivo. Biomaterials, 2013. 34(33): p. 8352-8360.
32. Schrand, A.M., et al., Differential biocompatibility of carbon nanotubes and nanodiamonds. Diamond and Related Materials, 2007. 16(12): p. 2118-2123.
33. Zhang, X.Y., et al., A comparative study of cellular uptake and cytotoxicity of multi-walled carbon nanotubes, graphene oxide, and nanodiamond. Toxicology Research, 2012. 1(1): p. 62-68.
34. Xing, Y., et al., DNA Damage in Embryonic Stem Cells Caused by Nanodiamonds. ACS Nano, 2011. 5(3): p. 2376-2384.
35. Blaber, S.P., et al., Effect of Labeling with Iron Oxide Particles or Nanodiamonds on the Functionality of Adipose-Derived Mesenchymal Stem Cells. Plos One, 2013. 8(1).
36. Wu, T.J., et al., Tracking the engraftment and regenerative capabilities of transplanted lung stem cells using fluorescent nanodiamonds. Nature Nanotechnology, 2013. 8(9): p. 682-689.
37. Li, H.C., et al., The hemocompatibility of oxidized diamond nanocrystals for biomedical applications. Scientific Reports, 2013. 3.
38. Kong, X.L., et al., High-Affinity Capture of Proteins by Diamond Nanoparticles for Mass Spectrometric Analysis. Analytical Chemistry, 2005. 77(1): p. 259-265.
39. Huang, L.C.L. and H.C. Chang, Adsorption and immobilization of cytochrome c on nanodiamonds. Langmuir, 2004. 20(14): p. 5879-5884.
40. Epperla, C.P., et al., Nanodiamond-Mediated Intercellular Transport of Proteins through Membrane Tunneling Nanotubes. Small, 2015. 11(45): p. 6097-6105.
41. Krueger, A. and D. Lang, Functionality is Key: Recent Progress in the Surface Modification of Nanodiamond. Advanced Functional Materials, 2012. 22(5): p. 890-906.
42. Nagl, A., S.R. Hemelaar, and R. Schirhagl, Improving surface and defect center chemistry of fluorescent nanodiamonds for imaging purposes-a review. Analytical and Bioanalytical Chemistry, 2015. 407(25): p. 7521-7536.
43. Krueger, A. and T. Boedeker, Deagglomeration and functionalisation of detonation nanodiamond with long alkyl chains. Diamond and Related Materials, 2008. 17(7-10): p. 1367-1370.
44. Krueger, A., et al., Biotinylated nanodiamond: Simple and efficient functionalization of detonation diamond. Langmuir, 2008. 24(8): p. 4200-4204.
45. Peters, T., Jr., Serum albumin. Adv Protein Chem, 1985. 37: p. 161-245.
46. Vinu, A., et al., Adsorption of Cytochrome C on New Mesoporous Carbon Molecular Sieves. The Journal of Physical Chemistry B, 2003. 107(33): p. 8297-8299.
47. Aramesh, M., et al., Surface charge effects in protein adsorption on nanodiamonds. Nanoscale, 2015. 7(13): p. 5726-5736.
48. Heim, R., A.B. Cubitt, and R.Y. Tsien, Improved green fluorescence. Nature, 1995. 373(6516): p. 663-664.
49. Ormo, M., et al., Crystal structure of the Aequorea victoria green fluorescent protein. Science, 1996. 273(5280): p. 1392-5.
50. Alberts B, J.A., Lewis J, et al., Molecular Biology of the Cell. 4th edition. New York: Garland Science, 2002.
51. Tsien, R.Y., The green fluorescent protein. Annual Review of Biochemistry, 1998. 67: p. 509-544.
52. Chang, C.-K., et al., Selective extraction and enrichment of multiphosphorylated peptides using polyarginine-coated diamond nanoparticles. Analytical Chemistry, 2008. 80(10): p. 3791-3797.
53. Link, S. and M.A. El-Sayed, Spectral properties and relaxation dynamics of surface plasmon electronic oscillations in gold and silver nanodots and nanorods. Journal of Physical Chemistry B, 1999. 103(40): p. 8410-8426.
54. Kelly, K.L., et al., The optical properties of metal nanoparticles: The influence of size, shape, and dielectric environment. Journal of Physical Chemistry B, 2003. 107(3): p. 668-677.
55. Moser, F., et al., Cellular Uptake of Gold Nanoparticles and Their Behavior as Labels for Localization Microscopy. Biophysical Journal, 2016. 110(4): p. 947-953.
56. Saha, K., et al., Gold Nanoparticles in Chemical and Biological Sensing. Chemical Reviews, 2012. 112(5): p. 2739-2779.
57. Yahia-Ammar, A., et al., Self-Assembled Gold Nanoclusters for Bright Fluorescence Imaging and Enhanced Drug Delivery. Acs Nano, 2016. 10(2): p. 2591-2599.
58. Abadeer, N.S. and C.J. Murphy, Recent Progress in Cancer Thermal Therapy Using Gold Nanoparticles. Journal of Physical Chemistry C, 2016. 120(9): p. 4691-4716.
59. El-Sayed, I.H., X. Huang, and M.A. El-Sayed, Selective laser photo-thermal therapy of epithelial carcinoma using anti-EGFR antibody conjugated gold nanoparticles. Cancer Lett, 2006. 239(1): p. 129-35.
60. Hirsch, L.R., et al., Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance. Proceedings of the National Academy of Sciences, 2003. 100(23): p. 13549-13554.
61. El-Sayed, I.H., X. Huang, and M.A. El-Sayed, Surface Plasmon Resonance Scattering and Absorption of anti-EGFR Antibody Conjugated Gold Nanoparticles in Cancer Diagnostics:  Applications in Oral Cancer. Nano Letters, 2005. 5(5): p. 829-834.
62. Tong, L., et al., Gold Nanorods Mediate Tumor Cell Death by Compromising Membrane Integrity. Advanced Materials, 2007. 19(20): p. 3136-3141.
63. Lee, J.Y., New and old roles of plasmodesmata in immunity and parallels to tunneling nanotubes. Plant Science, 2014. 221: p. 13-20.
64. Kumar, N.M. and N.B. Gilula, The gap junction communication channel. Cell, 1996. 84(3): p. 381-388.
65. Rustom, A., et al., Nanotubular highways for intercellular organelle transport. Science, 2004. 303(5660): p. 1007-1010.
66. Sisakhtnezhad, S. and L. Khosravi, Emerging physiological and pathological implications of tunneling nanotubes formation between cells. European Journal of Cell Biology, 2015. 94(10): p. 429-443.
67. Pyrgaki, C., et al., Dynamic imaging of mammalian neural tube closure. Developmental Biology, 2010. 344(2): p. 941-947.
68. Millard, T.H. and P. Martin, Dynamic analysis of filopodial interactions during the zippering phase of Drosophila dorsal closure. Development, 2008. 135(4): p. 621-626.
69. Caneparo, L., et al., Intercellular Bridges in Vertebrate Gastrulation. Plos One, 2011. 6(5).
70. Sowinski, S., et al., Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission. Nature Cell Biology, 2008. 10(2): p. 211-219.
71. Roberts, K.L., B. Manicassamy, and R.A. Lamb, Influenza A Virus Uses Intercellular Connections To Spread to Neighboring Cells. Journal of Virology, 2015. 89(3): p. 1537-1549.
72. Gousset, K., et al., Prions hijack tunnelling nanotubes for intercellular spread. Nature Cell Biology, 2009. 11(3): p. 328-U232.
73. Abounit, S., et al., Tunneling nanotubes spread fibrillar α-synuclein by intercellular trafficking of lysosomes. The EMBO Journal, 2016. 35(19): p. 2120-2138.
74. Dubey, G.P. and S. Ben-Yehuda, Intercellular Nanotubes Mediate Bacterial Communication. Cell, 2011. 144(4): p. 590-600.
75. Onfelt, B., et al., Structurally distinct membrane nanotubes between human macrophages support long-distance vesicular traffic or surfing of bacteria. Journal of Immunology, 2006. 177(12): p. 8476-8483.
76. Kadiu, I. and H.E. Gendelman, Macrophage Bridging Conduit Trafficking of HIV-1 Through the Endoplasmic Reticulum and Golgi Network. Journal of Proteome Research, 2011. 10(7): p. 3225-3238.
77. Smith, I.F., J.W. Shuai, and I. Parker, Active Generation and Propagation of Ca2+ Signals within Tunneling Membrane Nanotubes. Biophysical Journal, 2011. 100(8): p. L37-L39.
78. Mattila, P.K. and P. Lappalainen, Filopodia: molecular architecture and cellular functions. Nat Rev Mol Cell Biol, 2008. 9(6): p. 446-454.
79. Abounit, S. and C. Zurzolo, Wiring through tunneling nanotubes – from electrical signals to organelle transfer. Journal of Cell Science, 2012. 125(5): p. 1089-1098.
80. Wang, X., et al., Animal cells connected by nanotubes can be electrically coupled through interposed gap-junction channels. Proceedings of the National Academy of Sciences of the United States of America, 2010. 107(40): p. 17194-17199.
81. Lou, E., et al., Tunneling Nanotubes Provide a Unique Conduit for Intercellular Transfer of Cellular Contents in Human Malignant Pleural Mesothelioma. Plos One, 2012. 7(3).
82. Thayanithy, V., et al., Tumor-stromal cross talk: direct cell-to-cell transfer of oncogenic microRNAs via tunneling nanotubes. Translational Research, 2014. 164(5): p. 359-365.
83. Onfelt, B. and D.M. Davis, Can membrane nanotubes facilitate communication between immune cells? Biochemical Society Transactions, 2004. 32: p. 676-678.
84. Gurke, S., et al., Tunneling nanotube (TNT)-like structures facilitate a constitutive, actomyosin-dependent exchange of endocytic organelles between normal rat kidney cells. Experimental Cell Research, 2008. 314(20): p. 3669-3683.
85. Bukoreshtliev, N.V., et al., Selective block of tunneling nanotube (TNT) formation inhibits intercellular organelle transfer between PC12 cells. Febs Letters, 2009. 583(9): p. 1481-1488.
86. Koyanagi, M., et al., Cell-to-cell connection of endothelial progenitor cells with cardiac myocytes by nanotubes - A novel mechanism for cell fate changes? Circulation Research, 2005. 96(10): p. 1039-1041.
87. Cselenyak, A., et al., Mesenchymal stem cells rescue cardiomyoblasts from cell death in an in vitro ischemia model via direct cell-to-cell connections. Bmc Cell Biology, 2010. 11.
88. He, K.M., et al., Long-distance intercellular connectivity between cardiomyocytes and cardiofibroblasts mediated by membrane nanotubes. Cardiovascular Research, 2011. 92(1): p. 39-47.
89. Plotnikov, E.Y., et al., Cytoplasm and organelle transfer between mesenchymal multipotent stromal cells and renal tubular cells in co-culture. Experimental Cell Research, 2010. 316(15): p. 2447-2455.
90. Yasuda, K., et al., Tunneling nanotubes mediate rescue of prematurely senescent endothelial cells by endothelial progenitors: exchange of lysosomal pool. Aging-Us, 2011. 3(6): p. 597-608.
91. Watkins, S.C. and R.D. Salter, Functional connectivity between immune cells mediated by tunneling nanotubules. Immunity, 2005. 23(3): p. 309-318.
92. Kadiu, I. and H.E. Gendelman, Human Immunodeficiency Virus type 1 Endocytic Trafficking Through Macrophage Bridging Conduits Facilitates Spread of Infection. Journal of Neuroimmune Pharmacology, 2011. 6(4): p. 658-675.
93. Gousset, K. and C. Zurzolo, Tunnelling nanotubes. Prion, 2009. 3(2): p. 94-98.
94. Gousset, K. and C. Zurzolo, Tunnelling nanotubes A highway for prion spreading? Prion, 2009. 3(2): p. 94-98.
95. He, K.M., et al., Intercellular Transportation of Quantum Dots Mediated by Membrane Nanotubes. Acs Nano, 2010. 4(6): p. 3015-3022.
96. Ferrati, S., et al., Inter-endothelial Transport of Microvectors using Cellular Shuttles and Tunneling Nanotubes. Small, 2012. 8(20): p. 3151-3160.
97. Tosi, G., et al., Insight on the fate of CNS-targeted nanoparticles. Part II: Intercellular neuronal cell-to-cell transport. Journal of Controlled Release, 2014. 177: p. 96-107.
98. Chinnery, H.R., E. Pearlman, and P.G. McMenamin, Cutting edge: Membrane nanotubes in vivo: A feature of MHC class II+ cells in the mouse corneal. Journal of Immunology, 2008. 180(9): p. 5779-5783.
99. Teddy, J.M. and P.M. Kulesa, In vivo evidence for short- and long-range cell communication in cranial neural crest cells. Development, 2004. 131(24): p. 6141-6151.
100. McKinney, M.C., et al., Neural Crest Cell Communication Involves an Exchange of Cytoplasmic Material Through Cellular Bridges Revealed by Photoconversion of KikGR. Developmental Dynamics, 2011. 240(6): p. 1391-1401.
101. Rehberg, M., et al., Intercellular Transport of Nanomaterials is Mediated by Membrane Nanotubes In Vivo. Small, 2016. 12(14): p. 1882-1890.
102. Ho, V.M., J.A. Lee, and K.C. Martin, The Cell Biology of Synaptic Plasticity. Science, 2011. 334(6056): p. 623-628.
103. Todd, K.L., W.B. Kristan, and K.A. French, Gap Junction Expression Is Required for Normal Chemical Synapse Formation. Journal of Neuroscience, 2010. 30(45): p. 15277-15285.
104. Mese, G., G. Richard, and T.W. White, Gap junctions: Basic structure and function. Journal of Investigative Dermatology, 2007. 127(11): p. 2516-2524.
105. Hurtig, J., D.T. Chiu, and B. Onfelt, Intercellular nanotubes: insights from imaging studies and beyond. Wiley Interdisciplinary Reviews-Nanomedicine and Nanobiotechnology, 2010. 2(3): p. 260-276.
106. Saxton, M.J., Single-particle tracking: connecting the dots. Nature Methods, 2008. 5(8): p. 671-672.
107. Hell, S.W., Far-field optical nanoscopy. Science, 2007. 316(5828): p. 1153-1158.
108. Ueno, T. and T. Nagano, Fluorescent probes for sensing and imaging. Nature Methods, 2011. 8(8): p. 642-645.
109. Day, R.N. and M.W. Davidson, The fluorescent protein palette: tools for cellular imaging. Chemical Society Reviews, 2009. 38(10): p. 2887-2921.
110. Shaner, N.C., P.A. Steinbach, and R.Y. Tsien, A guide to choosing fluorescent proteins. Nature Methods, 2005. 2(12): p. 905-909.
111. Cui, B.X., et al., One at a time, live tracking of NGF axonal transport using quantum dots. Proceedings of the National Academy of Sciences of the United States of America, 2007. 104(34): p. 13666-13671.
112. Wang, Z.G., et al., Myosin-Driven Intercellular Transportation of Wheat Germ Agglutinin Mediated by Membrane Nanotubes between Human Lung Cancer Cells. Acs Nano, 2012. 6(11): p. 10033-10041.
113. Michalet, X., et al., Quantum Dots for Live Cells, in Vivo Imaging, and Diagnostics. Science, 2005. 307(5709): p. 538-544.
114. Derfus, A.M., W.C.W. Chan, and S.N. Bhatia, Probing the cytotoxicity of semiconductor quantum dots. Nano Letters, 2004. 4(1): p. 11-18.
115. Vaijayanthimala, V., et al., Nanodiamond-mediated drug delivery and imaging: challenges and opportunities. Expert Opinion on Drug Delivery, 2015. 12(5): p. 735-749.
116. Montalti, M., A. Cantelli, and G. Battistelli, Nanodiamonds and silicon quantum dots: ultrastable and biocompatible luminescent nanoprobes for long-term bioimaging. Chemical Society Reviews, 2015. 44(14): p. 4853-4921.
117. Faklaris, O., et al., Comparison of the photoluminescence properties of semiconductor quantum dots and non-blinking diamond nanoparticles. Observation of the diffusion of diamond nanoparticles in living cells. Journal of the European Optical Society-Rapid Publications, 2009. 4.
118. Fang, C.Y., et al., The Exocytosis of Fluorescent Nanodiamond and Its Use as a Long-Term Cell Tracker. Small, 2011. 7(23): p. 3363-3370.
119. Wang, D., et al., Transferrin-conjugated nanodiamond as an intracellular transporter of chemotherapeutic drug and targeting therapy for cancer cells. Ther Deliv, 2014. 5(5): p. 511-24.
120. Faklaris, O., et al., Photoluminescent Diamond Nanoparticles for Cell Labeling: Study of the Uptake Mechanism in Mammalian Cells. Acs Nano, 2009. 3(12): p. 3955-3962.
121. Tzeng, Y.K., et al., Superresolution Imaging of Albumin-Conjugated Fluorescent Nanodiamonds in Cells by Stimulated Emission Depletion. Angewandte Chemie-International Edition, 2011. 50(10): p. 2262-2265.
122. Holtzer, L., T. Meckel, and T. Schmidt, Nanometric three-dimensional tracking of individual quantum dots in cells. Applied Physics Letters, 2007. 90(5).
123. Constantinescu, R., et al., Neuronal differentiation and long-term culture of the human neuroblastoma line SH-SY5Y. Journal of Neural Transmission-Supplement, 2007(72): p. 17-28.
124. Krishna, A., et al., Systems genomics evaluation of the SH-SY5Y neuroblastoma cell line as a model for Parkinson's disease. Bmc Genomics, 2014. 15.
125. Kusumi, A., Y. Sako, and M. Yamamoto, Confined lateral diffusion of membrane-receptors as studied by single-particle tracking (nanovid microscopy) - effects of calcium-induced differentiation in cultured epithelial-cells. Biophysical Journal, 1993. 65(5): p. 2021-2040.
126. Sbalzarini, I.F. and P. Koumoutsakos, Feature point tracking and trajectory analysis for video imaging in cell biology. Journal of Structural Biology, 2005. 151(2): p. 182-195.
127. Dalby, B., et al., Advanced transfection with Lipofectamine 2000 reagent: primary neurons, siRNA, and high-throughput applications. Methods, 2004. 33(2): p. 95-103.
128. Rothman, J.E., Mechanism of intracellular protein-transport. Nature, 1994. 372(6501): p. 55-63.
129. Rechavi, O., I. Goldstein, and Y. Kloog, Intercellular exchange of proteins: The immune cell habit of sharing. Febs Letters, 2009. 583(11): p. 1792-1799.
130. Ahmed, K.A. and J. Xiang, Mechanisms of cellular communication through intercellular protein transfer. Journal of Cellular and Molecular Medicine, 2011. 15(7): p. 1458-1473.
131. Gerdes, H.H. and R.N. Carvalho, Intercellular transfer mediated by tunneling nanotubes. Current Opinion in Cell Biology, 2008. 20(4): p. 470-475.
132. Tomasz, M., Mitomycin-c - small, fast and deadly (but very selective). Chemistry & Biology, 1995. 2(9): p. 575-579.
133. Vernon, M.H.S.P.F.C.C., ed. A historical perspective on hyperthermia in oncology. In: Thermoradiotherapy and Thermochemotherapy. Springer Verlag, Berlin, Germany,. Vol. 1. 1995. 3-44.
134. Jaque, D., et al., Nanoparticles for photothermal therapies. Nanoscale, 2014. 6(16): p. 9494-9530.
135. Dutz, S. and R. Hergt, Magnetic particle hyperthermia-a promising tumour therapy? Nanotechnology, 2014. 25(45).
136. Gilchrist, R.K., et al., Selective inductive heating of lymph nodes. Annals of Surgery, 1957. 146(4): p. 596-606.
137. Dutz, S. and R. Hergt, Magnetic nanoparticle heating and heat transfer on a microscale: Basic principles, realities and physical limitations of hyperthermia for tumour therapy. International Journal of Hyperthermia, 2013. 29(8): p. 790-800.
138. Hergt, R. and S. Dutz, Magnetic particle hyperthermia-biophysical limitations of a visionary tumour therapy. Journal of Magnetism and Magnetic Materials, 2007. 311(1): p. 187-192.
139. Creixell, M., et al., EGFR-Targeted Magnetic Nanoparticle Heaters Kill Cancer Cells without a Perceptible Temperature Rise. Acs Nano, 2011. 5(9): p. 7124-7129.
140. Tong, L., et al., Gold nanorods mediate tumor cell death by compromising membrane integrity. Advanced Materials, 2007. 19(20): p. 3136-+.
141. Tsai, P.-C., et al., Gold/diamond nanohybrids for quantum sensing applications. EPJ Quantum Technology, 2015. 2(1): p. 19.
142. Huang, X.H., et al., Plasmonic photothermal therapy (PPTT) using gold nanoparticles. Lasers in Medical Science, 2008. 23(3): p. 217-228.
143. Ekici, O., et al., Thermal analysis of gold nanorods heated with femtosecond laser pulses. Journal of Physics D-Applied Physics, 2008. 41(18).
144. Acosta, V.M., et al., Temperature Dependence of the Nitrogen-Vacancy Magnetic Resonance in Diamond. Physical Review Letters, 2010. 104(7).
145. Toyli, D.M., et al., Measurement and Control of Single Nitrogen-Vacancy Center Spins above 600 K. Physical Review X, 2012. 2(3).
146. Chen, X.D., et al., Temperature dependent energy level shifts of nitrogen-vacancy centers in diamond. Applied Physics Letters, 2011. 99(16).
147. Doherty, M.W., et al., Temperature shifts of the resonances of the NV- center in diamond. Physical Review B, 2014. 90(4).
148. Balasubramanian, G., et al., Nitrogen-Vacancy color center in diamond - emerging nanoscale applications in bioimaging and biosensing. Current Opinion in Chemical Biology, 2014. 20: p. 69-77.
149. Tzeng, Y.K., et al., Time-Resolved Luminescence Nanothermometry with Nitrogen-Vacancy Centers in Nanodiamonds. Nano Letters, 2015. 15(6): p. 3945-3952.
150. Kucsko, G., et al., Nanometre-scale thermometry in a living cell. Nature, 2013. 500(7460): p. 54-U71.
151. Neumann, P., et al., High-Precision Nanoscale Temperature Sensing Using Single Defects in Diamond. Nano Letters, 2013. 13(6): p. 2738-2742.
152. Plakhotnik, T., H. Aman, and H.C. Chang, All-optical single-nanoparticle ratiometric thermometry with a noise floor of 0.3KHz(-1/2). Nanotechnology, 2015. 26(24).
153. Roti, J.L.R., Cellular responses to hyperthermia (40-46 degrees C): Cell killing and molecular events. International Journal of Hyperthermia, 2008. 24(1): p. 3-15.
154. Epperla, C.P., O.Y. Chen, and H.-C. Chang, Gold/diamond nanohybrids may reveal how hyperlocalized hyperthermia kills cancer cells. Nanomedicine, 2016. 11(5): p. 443-445.
155. Jaque, D. and F. Vetrone, Luminescence nanothermometry. Nanoscale, 2012. 4(15): p. 4301-4326.
156. Schirhagl, R., et al., Nitrogen-Vacancy Centers in Diamond: Nanoscale Sensors for Physics and Biology, in Annual Review of Physical Chemistry, Vol 65, M.A. Johnson and T.J. Martinez, Editors. 2014. p. 83-105.
157. Plakhotnik, T., et al., All-Optical Thermometry and Thermal Properties of the Optically Detected Spin Resonances of the NV- Center in Nanodiamond. Nano Letters, 2014. 14(9): p. 4989-4996.
158. Tetienne, J.-P., et al., Scanning Nanospin Ensemble Microscope for Nanoscale Magnetic and Thermal Imaging. Nano Letters, 2016. 16(1): p. 326-333.
159. Simanovskii, D.M., et al., Cellular tolerance to pulsed hyperthermia. Physical Review E, 2006. 74(1).
160. Davies, G., Vibronic spectra in diamond. Journal of Physics C-Solid State Physics, 1974. 7(20): p. 3797-3809.
161. Geissler, P.L., Temperature dependence of inhomogeneous broadening: On the meaning of isosbestic points. Journal of the American Chemical Society, 2005. 127(42): p. 14930-14935.
162. Urban, A.S., et al., Controlled Nanometric Phase Transitions of Phospholipid Membranes by Plasmonic Heating of Single Gold Nanoparticles. Nano Letters, 2009. 9(8): p. 2903-2908.
163. Delcea, M., et al., Nanoplasmonics for Dual-Molecule Release through Nanopores in the Membrane of Red Blood Cells. Acs Nano, 2012. 6(5): p. 4169-4180.
164. Sadtler, B. and A. Wei, Spherical ensembles of gold nanoparticles on silica: electrostatic and size effects. Chemical Communications, 2002(15): p. 1604-1605.
165. Pastoriza-Santos, I., et al., Optical properties of metal nanoparticle coated silica spheres: a simple effective medium approach. Physical Chemistry Chemical Physics, 2004. 6(21): p. 5056-5060.
166. Govorov, A.O. and H.H. Richardson, Generating heat with metal nanoparticles. Nano Today, 2007. 2(1): p. 30-38.
167. Davis, D.M. and S. Sowinski, Membrane nanotubes: dynamic long-distance connections between animal cells. Nature Reviews Molecular Cell Biology, 2008. 9(6): p. 431-436.
168. Costanzo, M. and C. Zurzolo, The cell biology of prion-like spread of protein aggregates: mechanisms and implication in neurodegeneration. Biochemical Journal, 2013. 452: p. 1-17.
169. Antkowiak, M., et al., Femtosecond optical transfection of individual mammalian cells. Nature Protocols, 2013. 8(6): p. 1216-1233.
170. Kost, T.A., J.P. Condreay, and D.L. Jarvis, Baculovirus as versatile vectors for protein expression in insect and mammalian cells. Nature Biotechnology, 2005. 23(5): p. 567-575.
171. Xiong, R., et al., Comparison of Gold Nanoparticle Mediated Photoporation: Vapor Nanobubbles Outperform Direct Heating for Delivering Macromolecules in Live Cells. ACS Nano, 2014. 8(6): p. 6288-6296.
172. Waring, M.J., Complex formation between ethidium bromide and nucleic acids. Journal of Molecular Biology, 1965. 13(1): p. 269-282.
173. Arndt-Jovin, D.J. and T.M. Jovin, Fluorescence labeling and microscopy of DNA. Methods Cell Biol, 1989. 30: p. 417-48.
174. Pontes, B., et al., Membrane Elastic Properties and Cell Function. Plos One, 2013. 8(7).
175. Hildebrandt, B., et al., The cellular and molecular basis of hyperthermia. Critical Reviews in Oncology Hematology, 2002. 43(1): p. 33-56.
176. Piñeiro, Y., et al., Iron Oxide Based Nanoparticles for Magnetic Hyperthermia Strategies in Biological Applications. European Journal of Inorganic Chemistry, 2015. 2015(27): p. 4495-4509.
177. Charras, G.T., A short history of blebbing. Journal of Microscopy-Oxford, 2008. 231(3): p. 466-478.
178. Ronchi, P., S. Terjung, and R. Pepperkok, At the cutting edge: applications and perspectives of laser nanosurgery in cell biology. Biological Chemistry, 2012. 393(4): p. 235-248.