去铁蛋白双金簇可控自组装及其生物医学成像的研究
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摘要
有良好生物兼容性,低毒性,和稳定性的可以靶向组织或细胞纳米结构在纳米生物医学上已经引起了很大的兴趣。本文成功用“点控制”的技术在去铁蛋白内部可控合成两个协同作用的可以经激发产生荧光的金簇。并通过测定荧光光谱,证实随着金簇尺寸的增大和之间距离的减少,两金簇之间的能量共振转移(Forster resonance energy transfer, FRET)会使两个金簇总的荧光强度逐渐增强,并使荧光光谱发生红移。通过冷冻电镜(Cryo-electron microscopy)和透射电镜(transmission electron microscopy)的低分辨,高分辨模式和扫描模式分别得到成对金簇在蛋白内部的直观图像。在扫描模式下还得到金元素的X射线能量散射图谱(energy-dispersive-X-ray spectroscopy, EDX)证明确实是在去铁蛋白中组装成功双金簇。通过测定Au-Ft (apoferritin-far-red Au cluster)的X-射线近边吸收峰,证明是在去铁蛋白的两个重链上组装上的双金簇。
成功的在有去铁蛋白受体的Caco-2细胞及小鼠的肾脏部位得到了特定的生物医学靶向荧光成像。这些实验结果表明,利用生物体本身存在的具有靶向功能的蛋白质和无机纳米材料组装体,有可能成为一种解决包括肿瘤在内的各种难以攻克疾病的诊断及治疗的潜在方法。相关文章已经被JACS (IF=8.58)接收。
Functional nanostructures with high biocompatibility and stability, low toxicity and specificity of targeting to desired organs or cells are of great interest in nanobiology and medicine. However, the challenge is to integrate all these desired features into a single nanobiostructure, which can be applied to biomedical applications and eventually in clinical settings. In this context, we designed a strategy to assemble two gold nanoclusters at the ferroxidase active sites of ferritin heavy chain. Our studies showed that the resulting nanostructures (Au-Ft) retain not only the intrinsic fluorescence properties of noble metal, but gain enhanced intensity, show a red-shift and exhibit tunable emissions due to the coupling interaction between the paired Au clusters. Furthermore, Au-Ft possessed the well defined nanostructure of native ferritin, showed organ-specific targeting ability, high biocompatibility and low cytotoxicity. The current study demonstrates that an integrated multimodal assembly strategy is able to generate stable and effective biomolecule-noble metal complexes of controllable size and with desirable fluorescence emission characteristics. Such agents are ideal for targeted in vitro and in vivo imaging. These results thus open new opportunities for biomolecule-guided nanostructure assembly with great potential for biomedical applications
In this paper, for making the idea of assembling the Au clusters into apoferritin to be true, the strategy which is used is "point controlling". Apoferritin is suitable to the condition which this idea needs:firstly, having the point which the reaction needs-the histidine at the ferroxidase active sites of apoferritin can bind Au3+ secondly, having the reactor which the reaction needs-the interior cavity of apoferritin is 10 nm, and the big pore of it is about 1 nm; thirdly, the chemical and physical characteristics of apoferritin are very stable, and the apoferritin can endure strong acid and alkali. By controlling the speed of the OH" reducing Au3+, we can get the size of the Au clusters we need.
Through cryo-EM, HAADF-STEM, HRTEM and so on we can prove that we have assembled paired far-red Au clusters in apoferritin..
Using the characteristic of far-red fluorescence of paired far-red Au clusters, we have done the research in the biomedical imaging:
(1) Paired far-red Au clusters used in the cell fluorescent imaging. We choose two kinds of cell, one is Caco-2 which has the receptor of apoferritin and the other is HepG2 which has no receptor of apoferritin. Paired far-red Au clusters within apoferritin can absorb on the surface of cell membrane of Caco-2, but can not absorb on the surface of cell membrane of HepG2.
(2) Paired far-red Au clusters used in the animal targeting fluorescent imaging. We can see the fluorescent imaging of the shape of two kidneys at the back of mice after several hours by vein injecting. It clearly says that paired far-red Au clusters reached the position of kidneys.
Through this paper it can confirm that far-red Au clusters within apoferritin can have a good prospect in the future.
成功的在有去铁蛋白受体的Caco-2细胞及小鼠的肾脏部位得到了特定的生物医学靶向荧光成像。这些实验结果表明,利用生物体本身存在的具有靶向功能的蛋白质和无机纳米材料组装体,有可能成为一种解决包括肿瘤在内的各种难以攻克疾病的诊断及治疗的潜在方法。相关文章已经被JACS (IF=8.58)接收。
Functional nanostructures with high biocompatibility and stability, low toxicity and specificity of targeting to desired organs or cells are of great interest in nanobiology and medicine. However, the challenge is to integrate all these desired features into a single nanobiostructure, which can be applied to biomedical applications and eventually in clinical settings. In this context, we designed a strategy to assemble two gold nanoclusters at the ferroxidase active sites of ferritin heavy chain. Our studies showed that the resulting nanostructures (Au-Ft) retain not only the intrinsic fluorescence properties of noble metal, but gain enhanced intensity, show a red-shift and exhibit tunable emissions due to the coupling interaction between the paired Au clusters. Furthermore, Au-Ft possessed the well defined nanostructure of native ferritin, showed organ-specific targeting ability, high biocompatibility and low cytotoxicity. The current study demonstrates that an integrated multimodal assembly strategy is able to generate stable and effective biomolecule-noble metal complexes of controllable size and with desirable fluorescence emission characteristics. Such agents are ideal for targeted in vitro and in vivo imaging. These results thus open new opportunities for biomolecule-guided nanostructure assembly with great potential for biomedical applications
In this paper, for making the idea of assembling the Au clusters into apoferritin to be true, the strategy which is used is "point controlling". Apoferritin is suitable to the condition which this idea needs:firstly, having the point which the reaction needs-the histidine at the ferroxidase active sites of apoferritin can bind Au3+ secondly, having the reactor which the reaction needs-the interior cavity of apoferritin is 10 nm, and the big pore of it is about 1 nm; thirdly, the chemical and physical characteristics of apoferritin are very stable, and the apoferritin can endure strong acid and alkali. By controlling the speed of the OH" reducing Au3+, we can get the size of the Au clusters we need.
Through cryo-EM, HAADF-STEM, HRTEM and so on we can prove that we have assembled paired far-red Au clusters in apoferritin..
Using the characteristic of far-red fluorescence of paired far-red Au clusters, we have done the research in the biomedical imaging:
(1) Paired far-red Au clusters used in the cell fluorescent imaging. We choose two kinds of cell, one is Caco-2 which has the receptor of apoferritin and the other is HepG2 which has no receptor of apoferritin. Paired far-red Au clusters within apoferritin can absorb on the surface of cell membrane of Caco-2, but can not absorb on the surface of cell membrane of HepG2.
(2) Paired far-red Au clusters used in the animal targeting fluorescent imaging. We can see the fluorescent imaging of the shape of two kidneys at the back of mice after several hours by vein injecting. It clearly says that paired far-red Au clusters reached the position of kidneys.
Through this paper it can confirm that far-red Au clusters within apoferritin can have a good prospect in the future.
引文
[1]Feshbach, H., Frontiers in Physics.. Science,1962.137(3533):p.846.
[2]Joynt, R., Many-body theory:the fractional quantum Hall effect. Science,1989. 245(4921):p.993.
[3]Weismann, A., et al., Seeing the Fermi surface in real space by nanoscale electron focusing. Science,2009.323(5918):p.1190-3.
[4]Hooley, C.A. and A.P. Mackenzie, Physics. Heavy fermions in the original Fermi liquid. Science,2007.317(5843):p.1332-3.
[5]Truscott, A.G., et al., Observation of Fermi pressure in a gas of trapped atoms. Science,2001.291(5513):p.2570-2.
[6]Pickett, W.E., et al., Fermi surfaces, fermi liquids, and high-temperature superconductors. Science,1992.255(5040):p.46-54.
[7]Mitragotri, S. and J. Lahann, Physical approaches to biomaterial design. Nat Mater,2009.8(1):p.15-23.
[8]Young, K.D., The selective value of bacterial shape. Microbiol Mol Biol Rev, 2006.70(3):p.660-703.
[9]Frojmovic, M.M. and J.G. Milton, Human platelet size, shape, and related functions in health and disease. Physiol Rev,1982.62(1):p.185-261.
[10]Rehfeldt, F., et al., Cell responses to the mechanochemical microenvironment--implications for regenerative medicine and drug delivery. Adv Drug Deliv Rev,2007.59(13):p.1329-39.
[11]Beningo, K.A. and Y.L. Wang, Fc-receptor-mediated phagocytosis is regulated by mechanical properties of the target. J Cell Sci,2002.115(Pt 4):p.849-56.
[12]Champion, J.A., A. Walker, and S. Mitragotri, Role of particle size in phagocytosis of polymeric microspheres. Pharm Res,2008.25(8):p.1815-21.
[13]Peer, D., et al., Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol,2007.2(12):p.751-60.
[14.Nishiyama, N., Nanomedicine:nanocarriers shape up for long life. Nat Nanotechnol,2007.2(4):p.203-4.
[15]Eisenberg, D., et al., Protein function in the post-genomic era. Nature,2000. 405(6788):p.823-6.
[16]Jaenicke, R., Molecular basis of protein function. Nature,1979.279(5712):p. 459-60.
[17]Klingenberg, M., Membrane protein oligomeric structure and transport function. Nature,1981.290(5806):p.449-54.
[18]LaVan, D.A., T. McGuire, and R. Langer, Small-scale systems for in vivo drug delivery. Nat Biotechnol,2003.21(10):p.1184-91.
[19]Arap, W., R. Pasqualini, and E. Ruoslahti, Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science,1998.279(5349):p. 377-80.
[20]Halin, C., et al., Enhancement of the antitumor activity of interleukin-12 by targeted delivery to neovasculature. Nat Biotechnol,2002.20(3):p.264-9.
[21]Dickson, D., UK scientists test liposome gene therapy technique. Nature,1993. 365(6441):p.4.
[22]Gregoriadis, G., Tailoring liposome structure. Nature,1980.283(5750):p.814-5.
[23]Radler, J.O., et al., Structure of DNA-cationic liposome complexes:DNA intercalation in multilamellar membranes in distinct interhelical packing regimes. Science,1997.275(5301):p.810-4.
[24]Weinstein, J.N., et al., Liposome-cell interaction:transfer and intracellular release of a trapped fluorescent marker. Science,1977.195(4277):p.489-92.
[25]Zheng, M., et al., Structure-based carbon nanotube sorting by sequence-dependent DNA assembly. Science,2003.302(5650):p.1545-8.
[26]Griffith, J.D., DNA structure:evidence from electron microscopy. Science,1978. 201(4355):p.525-7.
[27]Lehman, I.R., DNA ligase:structure, mechanism, and function. Science,1974. 186(4166):p.790-7.
[28]Sharma, J., et al., Control of self-assembly of DNA tubules through integration of gold nanoparticles. Science,2009.323(5910):p.112-6.
[29]Guo, P., The emerging field of RNA nanotechnology. Nat Nanotechnol,2010. 5(12):p.833-42.
[30]Famulok, M. and D. Ackermann, RNA nanotechnology:inspired by DNA. Nat Nanotechnol,2010.5(9):p.634-5.
[31]Clawson, G.A., et al., An RNA Sensor Platform for CTC Detection: Nanotechnology for Detection of Tumour Cell Marker RNAs. Bioforum Eur, 2009.13(1-2):p.10-11.
[32]Guo, P., RNA nanotechnology:engineering, assembly and applications in detection, gene delivery and therapy. J Nanosci Nanotechnol,2005.5(12):p. 1964-82.
[33]Khaled, A., et al., Controllable self-assembly of nanoparticles for specific delivery of multiple therapeutic molecules to cancer cells using RNA nanotechnology. Nano Lett,2005.5(9):p.1797-808.
[34]Shu, D., et al., Bottom-up Assembly of RNA Arrays and Superstructures as Potential Parts in Nanotechnology. Nano Lett,2004.4(9):p.1717-23.
[35]Amdursky, N., et al., Elementary building blocks of self-assembled peptide nanotubes. J Am Chem Soc,2010.132(44):p.15632-6.
[36]Zheng, J., P.R. Nicovich, and R.M. Dickson, Highly fluorescent noble-metal quantum dots. Annu Rev Phys Chem,2007.58:p.409-31.
[37]Turner, M., et al., Selective oxidation with dioxygen by gold nanoparticle catalysts derived from 55-atom clusters. Nature,2008.454(7207):p.981-3.
[38]Hashmi, A.S., Catalysis:raising the gold standard. Nature,2007.449(7160):p. 292-3.
[39]Gorin, D.J. and F.D. Toste, Relativistic effects in homogeneous gold catalysis. Nature,2007.446(7134):p.395-403.
[40]Nolan, S.P., Organic chemistry:catalytic gold rush. Nature,2007.445(7127):p. 496-7.
[41]Hughes, M.D., et al., Tunable gold catalysts for selective hydrocarbon oxidation under mild conditions. Nature,2005.437(7062):p.1132-5.
[42]Schmidbaur, H., Supramolecular chemistry. Going for gold. Nature,2001. 413(6851):p.31,33.
[43]Zope, B.N., et al., Reactivity of the gold/water interface during selective oxidation catalysis. Science,2010.330(6000):p.74-8.
[44]Christensen, C.H. and J.K. Norskov, Chemistry. Green gold catalysis. Science, 2010.327(5963):p.278-9.
[45]Grirrane, A., A. Corma, and H. Garcia, Gold-catalyzed synthesis of aromatic azo compounds from anilines and nitroaromatics. Science,2008.322(5908):p. 1661-4.
[46]Herzing, A.A., et al., Identification of active gold nanoclusters on iron oxide supports for CO oxidation. Science,2008.321(5894):p.1331-5.
[47]Zhang, J., et al., Stabilization of platinum oxygen-reduction electrocatalysts using gold clusters. Science,2007.315(5809):p.220-2.
[48]Corma, A. and P. Serna, Chemoselective hydrogenation of nitro compounds with supported gold catalysts. Science,2006.313(5785):p.332-4.
[49]Chen, M., et al., The promotional effect of gold in catalysis by palladium-gold. Science,2005.310(5746):p.291-3.
[50]Michalet, X., et al., Quantum dots for live cells, in vivo imaging, and diagnostics. Science,2005.307(5709):p.538-44.
[51]Rajh, T., Bio-functionalized quantum dots:tinkering with cell machinery. Nat Mater,2006.5(5):p.347-8.
[52]Clarke, S.J., et al., Photophysics of dopamine-modified quantum dots and effects on biological systems. Nat Mater,2006.5(5):p.409-17.
[53]Geim, A.K., Graphene:status and prospects. Science,2009.324(5934):p. 1530-4.
[54]Wei, Z., et al., Nanoscale tunable reduction of graphene oxide for graphene electronics. Science,2010.328(5984):p.1373-6.
[55]Prasher, R., Materials science. Graphene spreads the heat. Science,2010. 328(5975):p.185-6.
[56]Service, R.F., Materials science. Carbon sheets an atom thick give rise to graphene dreams. Science,2009.324(5929):p.875-7.
[57]Girit, C.O., et al., Graphene at the edge:stability and dynamics. Science,2009. 323(5922):p.1705-8.
[58]Li, D. and R.B. Kaner, Materials science. Graphene-based materials. Science, 2008.320(5880):p.1170-1.
[59]Westervelt, R.M., Applied physics. Graphene nanoelectronics. Science,2008. 320(5874):p.324-5.
[60]Li, X., et al., Chemically derived, ultrasmooth graphene nanoribbon semiconductors. Science,2008.319(5867):p.1229-32.
[61]Gogotsi, Y., Materials science. High-temperature rubber made from carbon nanotubes. Science,2010.330(6009):p.1332-3.
[62]Sholl, D.S. and J.K. Johnson, Materials science. Making high-flux membranes with carbon nanotubes. Science,2006.312(5776):p.1003-4.
[63]Chen, J.Y., et al., Electrowetting in carbon nanotubes. Science,2005.310(5753): p.1480-3.
[64]Welsher, K., et al., A route to brightly fluorescent carbon nanotubes for near-infrared imaging in mice. Nat Nanotechnol,2009.4(11):p.773-80.
[65]Nakayama, Y., et al., Tunable nanowire nonlinear optical probe. Nature,2007. 447(7148):p.1098-101.
[66]Gudiksen, M.S., et al., Growth of nanowire superlattice structures for nanoscale photonics and electronics. Nature,2002.415(6872):p.617-20.
[67]Morrow, T.J., et al., Programmed assembly of DNA-coated nanowire devices. Science,2009.323(5912):p.352.
[68]Melosh, N.A., et al., Ultrahigh-density nanowire lattices and circuits. Science, 2003.300(5616):p.112-5.
[69]Ma, D.D., et al., Small-diameter silicon nanowire surfaces. Science,2003. 299(5614):p.1874-7.
[70]Huang, M.H., et al., Room-temperature ultraviolet nanowire nanolasers. Science, 2001.292(5523):p.1897-9.
[71]Dong, A., et al., Binary nanocrystal superlattice membranes self-assembled at the liquid-air interface. Nature,2010.466(7305):p.474-7.
[72]Cai, J., et al., Atomically precise bottom-up fabrication of graphene nanoribbons. Nature,2010.466(7305):p.470-3.
[73]Krivanek, O.L., et al., Atom-by-atom structural and chemical analysis by annular dark-field electron microscopy. Nature,2010.464(7288):p.571-4.
[74]de Smit, E., et al., Nanoscale chemical imaging of a working catalyst by scanning transmission X-ray microscopy. Nature,2008.456(7219):p.222-5.
[75]Fujii, T., et al., Direct visualization of secondary structures of F-actin by electron cryomicroscopy. Nature,2010.467(7316):p.724-8.
[76]Baker, M., Whole-animal imaging:The whole picture. Nature,2010.463(7283): p.977-80.
[77]Shu, X., et al., Mammalian expression of infrared fluorescent proteins engineered from a bacterial phytochrome. Science,2009.324(5928):p.804-7.
[78]Wang, Z., et al., Structure of human ferritin L chain. Acta Crystallogr D Biol Crystallogr,2006.62(Pt 7):p.800-6.
[79]Granier, T., et al., Structure of mouse L-chain ferritin at 1.6 A resolution. Acta Crystallogr D Biol Crystallogr,2001.57(Pt 11):p.1491-7.
[80]Grant, R.A., et al., The crystal structure of Dps, a ferritin homolog that binds and protects DNA. Nat Struct Biol,1998.5(4):p.294-303.
[81]Lawson, D.M., et al., Solving the structure of human H ferritin by genetically engineering intermolecular crystal contacts. Nature,1991.349(6309):p.541-4.
[82]Marchetti, A., et al., Ferritin is used for iron storage in bloom-forming marine pennate diatoms. Nature,2009.457(7228):p.467-70.
[83]Benjaminson, M.A., et al., Ferritin-labelled enzyme:a tool for electron microscopy. Nature,1966.210(5042):p.1275-6.
[84]Crooker, S.A., et al., Spectrally resolved dynamics of energy transfer in quantum-dot assemblies:towards engineered energy flows in artificial materials. Phys Rev Lett,2002.89(18):p.186802.
[85]Koole, R., et al., Electronic coupling and exciton energy transfer in CdTe quantum-dot molecules. J Am Chem Soc,2006.128(32):p.10436-41.
[86]Nie, Z., A. Petukhova, and E. Kumacheva, Properties and emerging applications of self-assembled structures made from inorganic nanoparticles. Nat Nanotechnol,2010.5(1):p.15-25.
[87]Kalgaonkar, S. and B. Lonnerdal, Receptor-mediated uptake of ferritin-bound iron by human intestinal Caco-2 cells. J Nutr Biochem,2009.20(4):p.304-11.
[88]Chen, T.T., et al., TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis. J Exp Med,2005.202(7):p.955-65.
[89]Dimmock, E., D. Franks, and A.M. Glauert, The location of blood group antigen A on cultured rabbit kidney cells as revealed by ferritin-labelled antibody. J Cell Sci,1972.10(2):p.525-33.
[90]Maunsbach, A.B., Absorption of ferritin by rat kidney proximal tubule cells. Electron microscopic observations of the initial uptake phase in cells of microperfused single proximal tubules. J Ultrastruct Res,1966.16(1):p.1-12.
[91]Prokopenko, P.G., N.V. Makhlin, and S. Khaimchaev la, [Immunochemical studies of ferritin in kidney cancer]. Urol Nefrol (Mosk),1977(2):p.39-41.
[92]Rifkin, R.J. and P.A. Gahagan-Chase, Uptake of ferritin in rat kidney stimulated by renal and DOCA-induced hypertension. Am J Pathol,1971.62(3):p.429-42.
[2]Joynt, R., Many-body theory:the fractional quantum Hall effect. Science,1989. 245(4921):p.993.
[3]Weismann, A., et al., Seeing the Fermi surface in real space by nanoscale electron focusing. Science,2009.323(5918):p.1190-3.
[4]Hooley, C.A. and A.P. Mackenzie, Physics. Heavy fermions in the original Fermi liquid. Science,2007.317(5843):p.1332-3.
[5]Truscott, A.G., et al., Observation of Fermi pressure in a gas of trapped atoms. Science,2001.291(5513):p.2570-2.
[6]Pickett, W.E., et al., Fermi surfaces, fermi liquids, and high-temperature superconductors. Science,1992.255(5040):p.46-54.
[7]Mitragotri, S. and J. Lahann, Physical approaches to biomaterial design. Nat Mater,2009.8(1):p.15-23.
[8]Young, K.D., The selective value of bacterial shape. Microbiol Mol Biol Rev, 2006.70(3):p.660-703.
[9]Frojmovic, M.M. and J.G. Milton, Human platelet size, shape, and related functions in health and disease. Physiol Rev,1982.62(1):p.185-261.
[10]Rehfeldt, F., et al., Cell responses to the mechanochemical microenvironment--implications for regenerative medicine and drug delivery. Adv Drug Deliv Rev,2007.59(13):p.1329-39.
[11]Beningo, K.A. and Y.L. Wang, Fc-receptor-mediated phagocytosis is regulated by mechanical properties of the target. J Cell Sci,2002.115(Pt 4):p.849-56.
[12]Champion, J.A., A. Walker, and S. Mitragotri, Role of particle size in phagocytosis of polymeric microspheres. Pharm Res,2008.25(8):p.1815-21.
[13]Peer, D., et al., Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol,2007.2(12):p.751-60.
[14.Nishiyama, N., Nanomedicine:nanocarriers shape up for long life. Nat Nanotechnol,2007.2(4):p.203-4.
[15]Eisenberg, D., et al., Protein function in the post-genomic era. Nature,2000. 405(6788):p.823-6.
[16]Jaenicke, R., Molecular basis of protein function. Nature,1979.279(5712):p. 459-60.
[17]Klingenberg, M., Membrane protein oligomeric structure and transport function. Nature,1981.290(5806):p.449-54.
[18]LaVan, D.A., T. McGuire, and R. Langer, Small-scale systems for in vivo drug delivery. Nat Biotechnol,2003.21(10):p.1184-91.
[19]Arap, W., R. Pasqualini, and E. Ruoslahti, Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science,1998.279(5349):p. 377-80.
[20]Halin, C., et al., Enhancement of the antitumor activity of interleukin-12 by targeted delivery to neovasculature. Nat Biotechnol,2002.20(3):p.264-9.
[21]Dickson, D., UK scientists test liposome gene therapy technique. Nature,1993. 365(6441):p.4.
[22]Gregoriadis, G., Tailoring liposome structure. Nature,1980.283(5750):p.814-5.
[23]Radler, J.O., et al., Structure of DNA-cationic liposome complexes:DNA intercalation in multilamellar membranes in distinct interhelical packing regimes. Science,1997.275(5301):p.810-4.
[24]Weinstein, J.N., et al., Liposome-cell interaction:transfer and intracellular release of a trapped fluorescent marker. Science,1977.195(4277):p.489-92.
[25]Zheng, M., et al., Structure-based carbon nanotube sorting by sequence-dependent DNA assembly. Science,2003.302(5650):p.1545-8.
[26]Griffith, J.D., DNA structure:evidence from electron microscopy. Science,1978. 201(4355):p.525-7.
[27]Lehman, I.R., DNA ligase:structure, mechanism, and function. Science,1974. 186(4166):p.790-7.
[28]Sharma, J., et al., Control of self-assembly of DNA tubules through integration of gold nanoparticles. Science,2009.323(5910):p.112-6.
[29]Guo, P., The emerging field of RNA nanotechnology. Nat Nanotechnol,2010. 5(12):p.833-42.
[30]Famulok, M. and D. Ackermann, RNA nanotechnology:inspired by DNA. Nat Nanotechnol,2010.5(9):p.634-5.
[31]Clawson, G.A., et al., An RNA Sensor Platform for CTC Detection: Nanotechnology for Detection of Tumour Cell Marker RNAs. Bioforum Eur, 2009.13(1-2):p.10-11.
[32]Guo, P., RNA nanotechnology:engineering, assembly and applications in detection, gene delivery and therapy. J Nanosci Nanotechnol,2005.5(12):p. 1964-82.
[33]Khaled, A., et al., Controllable self-assembly of nanoparticles for specific delivery of multiple therapeutic molecules to cancer cells using RNA nanotechnology. Nano Lett,2005.5(9):p.1797-808.
[34]Shu, D., et al., Bottom-up Assembly of RNA Arrays and Superstructures as Potential Parts in Nanotechnology. Nano Lett,2004.4(9):p.1717-23.
[35]Amdursky, N., et al., Elementary building blocks of self-assembled peptide nanotubes. J Am Chem Soc,2010.132(44):p.15632-6.
[36]Zheng, J., P.R. Nicovich, and R.M. Dickson, Highly fluorescent noble-metal quantum dots. Annu Rev Phys Chem,2007.58:p.409-31.
[37]Turner, M., et al., Selective oxidation with dioxygen by gold nanoparticle catalysts derived from 55-atom clusters. Nature,2008.454(7207):p.981-3.
[38]Hashmi, A.S., Catalysis:raising the gold standard. Nature,2007.449(7160):p. 292-3.
[39]Gorin, D.J. and F.D. Toste, Relativistic effects in homogeneous gold catalysis. Nature,2007.446(7134):p.395-403.
[40]Nolan, S.P., Organic chemistry:catalytic gold rush. Nature,2007.445(7127):p. 496-7.
[41]Hughes, M.D., et al., Tunable gold catalysts for selective hydrocarbon oxidation under mild conditions. Nature,2005.437(7062):p.1132-5.
[42]Schmidbaur, H., Supramolecular chemistry. Going for gold. Nature,2001. 413(6851):p.31,33.
[43]Zope, B.N., et al., Reactivity of the gold/water interface during selective oxidation catalysis. Science,2010.330(6000):p.74-8.
[44]Christensen, C.H. and J.K. Norskov, Chemistry. Green gold catalysis. Science, 2010.327(5963):p.278-9.
[45]Grirrane, A., A. Corma, and H. Garcia, Gold-catalyzed synthesis of aromatic azo compounds from anilines and nitroaromatics. Science,2008.322(5908):p. 1661-4.
[46]Herzing, A.A., et al., Identification of active gold nanoclusters on iron oxide supports for CO oxidation. Science,2008.321(5894):p.1331-5.
[47]Zhang, J., et al., Stabilization of platinum oxygen-reduction electrocatalysts using gold clusters. Science,2007.315(5809):p.220-2.
[48]Corma, A. and P. Serna, Chemoselective hydrogenation of nitro compounds with supported gold catalysts. Science,2006.313(5785):p.332-4.
[49]Chen, M., et al., The promotional effect of gold in catalysis by palladium-gold. Science,2005.310(5746):p.291-3.
[50]Michalet, X., et al., Quantum dots for live cells, in vivo imaging, and diagnostics. Science,2005.307(5709):p.538-44.
[51]Rajh, T., Bio-functionalized quantum dots:tinkering with cell machinery. Nat Mater,2006.5(5):p.347-8.
[52]Clarke, S.J., et al., Photophysics of dopamine-modified quantum dots and effects on biological systems. Nat Mater,2006.5(5):p.409-17.
[53]Geim, A.K., Graphene:status and prospects. Science,2009.324(5934):p. 1530-4.
[54]Wei, Z., et al., Nanoscale tunable reduction of graphene oxide for graphene electronics. Science,2010.328(5984):p.1373-6.
[55]Prasher, R., Materials science. Graphene spreads the heat. Science,2010. 328(5975):p.185-6.
[56]Service, R.F., Materials science. Carbon sheets an atom thick give rise to graphene dreams. Science,2009.324(5929):p.875-7.
[57]Girit, C.O., et al., Graphene at the edge:stability and dynamics. Science,2009. 323(5922):p.1705-8.
[58]Li, D. and R.B. Kaner, Materials science. Graphene-based materials. Science, 2008.320(5880):p.1170-1.
[59]Westervelt, R.M., Applied physics. Graphene nanoelectronics. Science,2008. 320(5874):p.324-5.
[60]Li, X., et al., Chemically derived, ultrasmooth graphene nanoribbon semiconductors. Science,2008.319(5867):p.1229-32.
[61]Gogotsi, Y., Materials science. High-temperature rubber made from carbon nanotubes. Science,2010.330(6009):p.1332-3.
[62]Sholl, D.S. and J.K. Johnson, Materials science. Making high-flux membranes with carbon nanotubes. Science,2006.312(5776):p.1003-4.
[63]Chen, J.Y., et al., Electrowetting in carbon nanotubes. Science,2005.310(5753): p.1480-3.
[64]Welsher, K., et al., A route to brightly fluorescent carbon nanotubes for near-infrared imaging in mice. Nat Nanotechnol,2009.4(11):p.773-80.
[65]Nakayama, Y., et al., Tunable nanowire nonlinear optical probe. Nature,2007. 447(7148):p.1098-101.
[66]Gudiksen, M.S., et al., Growth of nanowire superlattice structures for nanoscale photonics and electronics. Nature,2002.415(6872):p.617-20.
[67]Morrow, T.J., et al., Programmed assembly of DNA-coated nanowire devices. Science,2009.323(5912):p.352.
[68]Melosh, N.A., et al., Ultrahigh-density nanowire lattices and circuits. Science, 2003.300(5616):p.112-5.
[69]Ma, D.D., et al., Small-diameter silicon nanowire surfaces. Science,2003. 299(5614):p.1874-7.
[70]Huang, M.H., et al., Room-temperature ultraviolet nanowire nanolasers. Science, 2001.292(5523):p.1897-9.
[71]Dong, A., et al., Binary nanocrystal superlattice membranes self-assembled at the liquid-air interface. Nature,2010.466(7305):p.474-7.
[72]Cai, J., et al., Atomically precise bottom-up fabrication of graphene nanoribbons. Nature,2010.466(7305):p.470-3.
[73]Krivanek, O.L., et al., Atom-by-atom structural and chemical analysis by annular dark-field electron microscopy. Nature,2010.464(7288):p.571-4.
[74]de Smit, E., et al., Nanoscale chemical imaging of a working catalyst by scanning transmission X-ray microscopy. Nature,2008.456(7219):p.222-5.
[75]Fujii, T., et al., Direct visualization of secondary structures of F-actin by electron cryomicroscopy. Nature,2010.467(7316):p.724-8.
[76]Baker, M., Whole-animal imaging:The whole picture. Nature,2010.463(7283): p.977-80.
[77]Shu, X., et al., Mammalian expression of infrared fluorescent proteins engineered from a bacterial phytochrome. Science,2009.324(5928):p.804-7.
[78]Wang, Z., et al., Structure of human ferritin L chain. Acta Crystallogr D Biol Crystallogr,2006.62(Pt 7):p.800-6.
[79]Granier, T., et al., Structure of mouse L-chain ferritin at 1.6 A resolution. Acta Crystallogr D Biol Crystallogr,2001.57(Pt 11):p.1491-7.
[80]Grant, R.A., et al., The crystal structure of Dps, a ferritin homolog that binds and protects DNA. Nat Struct Biol,1998.5(4):p.294-303.
[81]Lawson, D.M., et al., Solving the structure of human H ferritin by genetically engineering intermolecular crystal contacts. Nature,1991.349(6309):p.541-4.
[82]Marchetti, A., et al., Ferritin is used for iron storage in bloom-forming marine pennate diatoms. Nature,2009.457(7228):p.467-70.
[83]Benjaminson, M.A., et al., Ferritin-labelled enzyme:a tool for electron microscopy. Nature,1966.210(5042):p.1275-6.
[84]Crooker, S.A., et al., Spectrally resolved dynamics of energy transfer in quantum-dot assemblies:towards engineered energy flows in artificial materials. Phys Rev Lett,2002.89(18):p.186802.
[85]Koole, R., et al., Electronic coupling and exciton energy transfer in CdTe quantum-dot molecules. J Am Chem Soc,2006.128(32):p.10436-41.
[86]Nie, Z., A. Petukhova, and E. Kumacheva, Properties and emerging applications of self-assembled structures made from inorganic nanoparticles. Nat Nanotechnol,2010.5(1):p.15-25.
[87]Kalgaonkar, S. and B. Lonnerdal, Receptor-mediated uptake of ferritin-bound iron by human intestinal Caco-2 cells. J Nutr Biochem,2009.20(4):p.304-11.
[88]Chen, T.T., et al., TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis. J Exp Med,2005.202(7):p.955-65.
[89]Dimmock, E., D. Franks, and A.M. Glauert, The location of blood group antigen A on cultured rabbit kidney cells as revealed by ferritin-labelled antibody. J Cell Sci,1972.10(2):p.525-33.
[90]Maunsbach, A.B., Absorption of ferritin by rat kidney proximal tubule cells. Electron microscopic observations of the initial uptake phase in cells of microperfused single proximal tubules. J Ultrastruct Res,1966.16(1):p.1-12.
[91]Prokopenko, P.G., N.V. Makhlin, and S. Khaimchaev la, [Immunochemical studies of ferritin in kidney cancer]. Urol Nefrol (Mosk),1977(2):p.39-41.
[92]Rifkin, R.J. and P.A. Gahagan-Chase, Uptake of ferritin in rat kidney stimulated by renal and DOCA-induced hypertension. Am J Pathol,1971.62(3):p.429-42.