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Nanomedicine: Tiny Particles and Machines Give Huge Gains

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Abstract

Nanomedicine is an emerging field that integrates nanotechnology, biomolecular engineering, life sciences and medicine; it is expected to produce major breakthroughs in medical diagnostics and therapeutics. Nano-scale structures and devices are compatible in size with proteins and nucleic acids in living cells. Therefore, the design, characterization and application of nano-scale probes, carriers and machines may provide unprecedented opportunities for achieving a better control of biological processes, and drastic improvements in disease detection, therapy, and prevention. Recent advances in nanomedicine include the development of nanoparticle (NP)-based probes for molecular imaging, nano-carriers for drug/gene delivery, multifunctional NPs for theranostics, and molecular machines for biological and medical studies. This article provides an overview of the nanomedicine field, with an emphasis on NPs for imaging and therapy, as well as engineered nucleases for genome editing. The challenges in translating nanomedicine approaches to clinical applications are discussed.

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References

  1. Alexiou, C., et al. Locoregional cancer treatment with magnetic drug targeting. Cancer Res. 60:6641–6648, 2000.

    CAS  PubMed  Google Scholar 

  2. Alivisatos, P. The use of nanocrystals in biological detection. Nat. Biotechnol. 22:47–52, 2004.

    CAS  PubMed  Google Scholar 

  3. Alivisatos, A. P., W. Gu, and C. Larabell. Quantum dots as cellular probes. Annu. Rev. Biomed. Eng. 7:55–76, 2005.

    CAS  PubMed  Google Scholar 

  4. Bao, G., S. Mitragotri, and S. Tong. Multifunctional nanoparticles for drug delivery and molecular imaging. Annu. Rev. Biomed. 15:253–282, 2013.

    Google Scholar 

  5. Bertolini, L. R., et al. Transient depletion of Ku70 and Xrcc4 by RNAi as a means to manipulate the non-homologous end-joining pathway. J. Biotechnol. 128:246–257, 2007.

    CAS  PubMed  Google Scholar 

  6. Bitinaite, J., D. A. Wah, A. K. Aggarwal, and I. Schildkraut. FokI dimerization is required for DNA cleavage. Proc. Natl. Acad. Sci. USA 95:10570–10575, 1998.

    CAS  PubMed  Google Scholar 

  7. Bjornerud, A., et al. Use of intravascular contrast agents in MRI. Acad. Radiol. 5(Suppl 1):S223–S225, 1998.

    PubMed  Google Scholar 

  8. Boch, J., et al. Breaking the code of DNA binding specificity of TAL-type III effectors. Science 326:1509–1512, 2009.

    CAS  PubMed  Google Scholar 

  9. Bolotin, A., B. Quinquis, A. Sorokin, and S. D. Ehrlich. Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin. Microbiology 151:2551–2561, 2005.

    CAS  PubMed  Google Scholar 

  10. Bonasio, R., et al. Specific and covalent labeling of a membrane protein with organic fluorochromes and quantum dots. Proc. Natl. Acad. Sci. USA 104:14753–14758, 2007.

    CAS  PubMed  Google Scholar 

  11. Boyer, D., P. Tamarat, A. Maali, B. Lounis, and M. Orrit. Photothermal imaging of nanometer-sized metal particles among scatterers. Science 297:1160–1163, 2002.

    CAS  PubMed  Google Scholar 

  12. Brooks, R. A., F. Moiny, and P. Gillis. On T2-shortening by weakly magnetized particles: the chemical exchange model. Magn. Reson. Med. 45:1014–1020, 2001.

    CAS  PubMed  Google Scholar 

  13. Bruchez, M., M. Moronne, P. Gin, S. Weiss, and A. P. Alivisatos. Semiconductor nanocrystals as fluorescent biological labels. Science 281:2013–2016, 1998.

    CAS  PubMed  Google Scholar 

  14. Brunetti, V., et al. InP/ZnS as a safer alternative to CdSe/ZnS core/shell quantum dots: in vitro and in vivo toxicity assessment. Nanoscale 5:307–317, 2013.

    CAS  PubMed  Google Scholar 

  15. Busa, W. B., and R. Nuccitelli. Metabolic regulation via intracellular pH. Am. J. Physiol. 246:R409–R438, 1984.

    CAS  PubMed  Google Scholar 

  16. Caldorera-Moore, M., and N. A. Peppas. Micro- and nanotechnologies for intelligent and responsive biomaterial-based medical systems. Adv. Drug Deliv. Rev. 61:1391–1401, 2009.

    CAS  PubMed Central  PubMed  Google Scholar 

  17. Carmeliet, P. Angiogenesis in health and disease. Nat. Med. 9:653–660, 2003.

    CAS  PubMed  Google Scholar 

  18. Champion, J. A., Y. K. Katare, and S. Mitragotri. Particle shape: a new design parameter for micro- and nanoscale drug delivery carriers. J. Controlled Release Off. J. Controlled Release Soc. 121:3–9, 2007.

    CAS  Google Scholar 

  19. Chan, W. C., and S. Nie. Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 281:2016–2018, 1998.

    CAS  PubMed  Google Scholar 

  20. Chan, W. C. W., T. L. Prendergast, M. Jain, and S. Nie. One-step conjugation of biomolecules to luminescent nanocrystals. Proc. SPIE 3924:2–9, 2000.

    CAS  Google Scholar 

  21. Chang, E., et al. Protease-activated quantum dot probes. Biochem. Biophys. Res. Commun. 334:1317–1321, 2005.

    CAS  PubMed  Google Scholar 

  22. Chattopadhyay, P. K., et al. Quantum dot semiconductor nanocrystals for immunophenotyping by polychromatic flow cytometry. Nat. Med. 12:972–977, 2006.

    CAS  PubMed  Google Scholar 

  23. Cheng, Z., A. Al Zaki, J. Z. Hui, V. R. Muzykantov, and A. Tsourkas. Multifunctional nanoparticles: cost versus benefit of adding targeting and imaging capabilities. Science 338:903–910, 2012.

    CAS  PubMed Central  PubMed  Google Scholar 

  24. Chilkoti, A., M. R. Dreher, D. E. Meyer, and D. Raucher. Targeted drug delivery by thermally responsive polymers. Adv. Drug Deliv. Rev. 54:613–630, 2002.

    CAS  PubMed  Google Scholar 

  25. Cho, M. H., et al. A magnetic switch for the control of cell death signalling in in vitro and in vivo systems. Nat. Mater. 11:1038–1043, 2012.

    CAS  PubMed  Google Scholar 

  26. Choi, J. S., et al. Self-confirming “AND” logic nanoparticles for fault-free MRI. J. Am. Chem. Soc. 132:11015–11017, 2010.

    CAS  PubMed Central  PubMed  Google Scholar 

  27. Christian, M. L., et al. Targeting G with TAL effectors: a comparison of activities of TALENs constructed with NN and NK repeat variable di-residues. Plos One 7:e45383, 2012.

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Clapp, A. R., et al. Quantum dot-based multiplexed fluorescence resonance energy transfer. J. Am. Chem. Soc. 127:18212–18221, 2005.

    CAS  PubMed  Google Scholar 

  29. Clement, O., N. Siauve, C. A. Cuenod, and G. Frija. Liver imaging with ferumoxides (Feridex): fundamentals, controversies, and practical aspects. Top. Magn. Reson. Imaging TMRI 9:167–182, 1998.

    CAS  Google Scholar 

  30. Cong, L., R. Zhou, Y. C. Kuo, M. Cunniff, and F. Zhang. Comprehensive interrogation of natural TALE DNA-binding modules and transcriptional repressor domains. Nat. Commun. 3:968, 2012.

    PubMed Central  PubMed  Google Scholar 

  31. Cong, L., et al. Multiplex genome engineering using CRISPR/Cas systems. Science 339:819–823, 2013.

    CAS  PubMed Central  PubMed  Google Scholar 

  32. Cornu, T. I., et al. DNA-binding specificity is a major determinant of the activity and toxicity of zinc-finger nucleases. Mol. Ther. J. Am. Soc. Gene Ther. 16:352–358, 2008.

    CAS  Google Scholar 

  33. Cradick, T. J., G. Ambrosini, C. Iseli, P. Bucher, and A. P. McCaffrey. ZFN-Site searches genomes for zinc finger nuclease target sites and off-target sites. BMC Bioinform. 12:152, 2011.

    CAS  Google Scholar 

  34. Cradick, T. J., E. J. Fine, C. J. Antico, and G. Bao. CRISPR/Cas9 systems targeting β-globin and CCR5 genes have substantial off-target activity. Nucleic Acids Res. 41:9584–9592, 2013.

    Google Scholar 

  35. Cristea, S., et al. In vivo cleavage of transgene donors promotes nuclease-mediated targeted integration. Biotechnol. Bioeng. 110:871–880, 2013.

    CAS  PubMed  Google Scholar 

  36. Dam, D. H., K. S. Culver, P. N. Sisco, and T. W. Odom. Shining light on nuclear-targeted therapy using gold nanostar constructs. Ther. Deliv. 3:1263–1267, 2012.

    CAS  PubMed Central  PubMed  Google Scholar 

  37. Dames, P., et al. Targeted delivery of magnetic aerosol droplets to the lung. Nat. Nanotechnol. 2:495–499, 2007.

    PubMed  Google Scholar 

  38. Dennis, A. M., and G. Bao. Quantum dot-fluorescent protein pairs as novel fluorescence resonance energy transfer probes. Nano Lett. 8:1439–1445, 2008.

    CAS  PubMed  Google Scholar 

  39. Dennis, A. M., W. J. Rhee, D. Sotto, S. N. Dublin, and G. Bao. Quantum dot-fluorescent protein FRET probes for sensing intracellular pH. ACS Nano 6:2917–2924, 2012.

    CAS  PubMed Central  PubMed  Google Scholar 

  40. Dilnawaz, F., A. Singh, C. Mohanty, and S. K. Sahoo. Dual drug loaded superparamagnetic iron oxide nanoparticles for targeted cancer therapy. Biomaterials 31:3694–3706, 2010.

    CAS  PubMed  Google Scholar 

  41. Doshi, N., and S. Mitragotri. Designer biomaterials for nanomedicine. Adv. Funct. Mater. 19:3843–3854, 2009.

    CAS  Google Scholar 

  42. Doyon, Y., et al. Enhancing zinc-finger-nuclease activity with improved obligate heterodimeric architectures. Nat. Methods 8:74–79, 2010.

    PubMed  Google Scholar 

  43. Dreier, B., D. J. Segal, and C. F. Barbas, 3rd. Insights into the molecular recognition of the 5′-GNN-3′ family of DNA sequences by zinc finger domains. J. Mol. Biol. 303:489–502, 2000.

    CAS  PubMed  Google Scholar 

  44. Dubertret, B., et al. In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science 298:1759–1762, 2002.

    CAS  PubMed  Google Scholar 

  45. Engvall, E., and P. Perlmann. Enzyme-linked immunosorbent assay (ELISA) quantitative assay of immunoglobulin-G. Immunochemistry 8:871–874, 1971.

    CAS  PubMed  Google Scholar 

  46. Euliss, L. E., J. A. DuPont, S. Gratton, and J. DeSimone. Imparting size, shape, and composition control of materials for nanomedicine. Chem. Soc. Rev. 35:1095–1104, 2006.

    CAS  PubMed  Google Scholar 

  47. Fortin, J. P., et al. Size-sorted anionic iron oxide nanomagnets as colloidal mediators for magnetic hyperthermia. J. Am. Chem. Soc. 129:2628–2635, 2007.

    CAS  PubMed  Google Scholar 

  48. Fu, Y., et al. High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nat. Biotechnol. 31:822–826, 2013.

    Google Scholar 

  49. Gannon, C. J., C. R. Patra, R. Bhattacharya, P. Mukherjee, and S. A. Curley. Intracellular gold nanoparticles enhance non-invasive radiofrequency thermal destruction of human gastrointestinal cancer cells. J. Nanobiotechnol. 6:2, 2008.

    Google Scholar 

  50. Gao, X., Y. Cui, R. M. Levenson, L. W. Chung, and S. Nie. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat. Biotechnol. 22:969–976, 2004.

    CAS  PubMed  Google Scholar 

  51. Garneau, J. E., et al. The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. Nature 468:67–71, 2010.

    CAS  PubMed  Google Scholar 

  52. Garon, E. B., et al. Quantum dot labeling and tracking of human leukemic, bone marrow and cord blood cells. Leuk. Res. 31:643–651, 2007.

    CAS  PubMed  Google Scholar 

  53. Gillis, P., and S. H. Koenig. Transverse relaxation of solvent protons induced by magnetized spheres: application to ferritin, erythrocytes, and magnetite. Magn. Reson. Med. 5:323–345, 1987.

    CAS  PubMed  Google Scholar 

  54. Gillis, P., F. Moiny, and R. A. Brooks. On T(2)-shortening by strongly magnetized spheres: a partial refocusing model. Magn. Reson. Med. 47:257–263, 2002.

    PubMed  Google Scholar 

  55. Gobin, A. M., et al. Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer therapy. Nano Lett. 7:1929–1934, 2007.

    CAS  PubMed  Google Scholar 

  56. Goldman, E. R., et al. Conjugation of luminescent quantum dots with antibodies using an engineered adaptor protein to provide new reagents for fluoroimmunoassays. Anal. Chem. 74:841–847, 2002.

    CAS  PubMed  Google Scholar 

  57. Guthi, J. S., et al. MRI-visible micellar nanomedicine for targeted drug delivery to lung cancer cells. Mol. Pharm. 7:32–40, 2010.

    CAS  PubMed Central  PubMed  Google Scholar 

  58. Halas, N. J. Playing with plasmons. Tuning the optical resonant properties of metallic nanoshells. Mrs. Bull. 30:362–367, 2005.

    CAS  Google Scholar 

  59. Hale, C. R., et al. RNA-guided RNA cleavage by a CRISPR RNA-Cas protein complex. Cell 139:945–956, 2009.

    CAS  PubMed Central  PubMed  Google Scholar 

  60. Hama, Y., Y. Koyama, Y. Urano, P. L. Choyke, and H. Kobayashi. Simultaneous two-color spectral fluorescence lymphangiography with near infrared quantum dots to map two lymphatic flows from the breast and the upper extremity. Breast Cancer Res. Treat 103:23–28, 2007.

    PubMed  Google Scholar 

  61. Hanna, J., et al. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 318:1920–1923, 2007.

    CAS  PubMed  Google Scholar 

  62. Herrmann, F., et al. p53 gene repair with zinc finger nucleases optimised by yeast 1-hybrid and validated by Solexa Sequencing. Plos One 6:e20913, 2011.

    Google Scholar 

  63. Hirsch, L. R., et al. Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance. Proc. Natl. Acad. Sci. USA 100:13549–13554, 2003.

    CAS  PubMed  Google Scholar 

  64. Hong, G., et al. In vivo fluorescence imaging with Ag2S quantum dots in the second near-infrared region. Angew. Chem. Int. Ed. Engl. 51:9818–9821, 2012.

    CAS  PubMed  Google Scholar 

  65. Hook, A. L., et al. High throughput methods applied in biomaterial development and discovery. Biomaterials 31:187–198, 2010.

    CAS  PubMed  Google Scholar 

  66. Horvath, P., and R. Barrangou. CRISPR/Cas, the immune system of bacteria and archaea. Science 327:167–170, 2010.

    CAS  PubMed  Google Scholar 

  67. Howarth, M., K. Takao, Y. Hayashi, and A. Y. Ting. Targeting quantum dots to surface proteins in living cells with biotin ligase. Proc. Natl. Acad. Sci. USA 102:7583–7588, 2005.

    CAS  PubMed  Google Scholar 

  68. Hsu, P. D., et al. DNA targeting specificity of RNA-guided Cas9 nucleases. Nat. Biotechnol. 31:827–832, 2013.

    Google Scholar 

  69. Huang, X. H., I. H. El-Sayed, W. Qian, and M. A. El-Sayed. Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. J. Am. Chem. Soc. 128:2115–2120, 2006.

    CAS  PubMed  Google Scholar 

  70. Jain, P. K., X. H. Huang, I. H. El-Sayed, and M. A. El-Sayed. Noble metals on the nanoscale: optical and photothermal properties and some applications in imaging, sensing, biology, and medicine. Acc. Chem. Res. 41:1578–1586, 2008.

    CAS  PubMed  Google Scholar 

  71. Jain, P. K., K. S. Lee, I. H. El-Sayed, and M. A. El-Sayed. Calculated absorption and scattering properties of gold nanoparticles of different size, shape, and composition: applications in biological imaging and biomedicine. J. Phys. Chem. B 110:7238–7248, 2006.

    CAS  PubMed  Google Scholar 

  72. Jain, T. K., et al. Magnetic nanoparticles with dual functional properties: drug delivery and magnetic resonance imaging. Biomaterials 29:4012–4021, 2008.

    CAS  PubMed Central  PubMed  Google Scholar 

  73. Jaiswal, J. K., H. Mattoussi, J. M. Mauro, and S. M. Simon. Long-term multiple color imaging of live cells using quantum dot bioconjugates. Nat. Biotechnol. 21:47–51, 2003.

    CAS  PubMed  Google Scholar 

  74. Jamieson, A. C., S. H. Kim, and J. A. Wells. In vitro selection of zinc fingers with altered DNA-binding specificity. Biochemistry 33:5689–5695, 1994.

    CAS  PubMed  Google Scholar 

  75. Jana, N. R., Y. F. Chen, and X. G. Peng. Size- and shape-controlled magnetic (Cr, Mn, Fe, Co, Ni) oxide nanocrystals via a simple and general approach. Chem. Mater. 16:3931–3935, 2004.

    CAS  Google Scholar 

  76. Jang, J. T., et al. Critical enhancements of MRI contrast and hyperthermic effects by dopant-controlled magnetic nanoparticles. Angew. Chem. Int. Ed. 48:1234–1238, 2009.

    CAS  Google Scholar 

  77. Joung, J. K., E. I. Ramm, and C. O. Pabo. A bacterial two-hybrid selection system for studying protein-DNA and protein–protein interactions. Proc. Natl. Acad. Sci. USA 97:7382–7387, 2000.

    CAS  PubMed  Google Scholar 

  78. Jun, Y. W., J. W. Seo, and A. Cheon. Nanoscaling laws of magnetic nanoparticles and their applicabilities in biomedical sciences. Acc. Chem. Res. 41:179–189, 2008.

    CAS  PubMed  Google Scholar 

  79. Jun, Y. W., et al. Nanoscale size effect of magnetic nanocrystals and their utilization for cancer diagnosis via magnetic resonance imaging. J. Am. Chem. Soc. 127:5732–5733, 2005.

    CAS  PubMed  Google Scholar 

  80. Kim, Y. G., and S. Chandrasegaran. Chimeric restriction endonuclease. Proc. Natl. Acad. Sci. USA 91:883–887, 1994.

    CAS  PubMed  Google Scholar 

  81. Kim, J. S., and C. O. Pabo. Getting a handhold on DNA: design of poly-zinc finger proteins with femtomolar dissociation constants. Proc. Natl. Acad. Sci. USA 95:2812–2817, 1998.

    CAS  PubMed  Google Scholar 

  82. Kim, B. Y., J. T. Rutka, and W. C. Chan. Nanomedicine. N. Engl. J. Med. 363:2434–2443, 2010.

    CAS  PubMed  Google Scholar 

  83. Kim, J., et al. Multifunctional uniform nanoparticles composed of a magnetite nanocrystal core and a mesoporous silica shell for magnetic resonance and fluorescence imaging and for drug delivery. Angew. Chem. Int. Ed. Engl. 47:8438–8441, 2008.

    CAS  PubMed  Google Scholar 

  84. Koenig, S. H., and K. E. Kellar. Theory of 1/T1 and 1/T2 NMRD profiles of solutions of magnetic nanoparticles. Magn. Reson. Med. 34:227–233, 1995.

    CAS  PubMed  Google Scholar 

  85. Krishnan, K. M., et al. Nanomagnetism and spin electronics: materials, microstructure and novel properties. J. Mater. Sci. 41:793–815, 2006.

    CAS  Google Scholar 

  86. Landázuri, N., et al. Magnetic targeting of human mesenchymal stem cells with internalized superparamagnetic iron oxide nanoparticles. Small, 2013. doi:10.1002/smll.201300570.

  87. Lee, C. M., R. Flynn, J. A. Hollywood, M. F. Scallan, and P. T. Harrison. Correction of the ∆F508 mutation in the cystic fibrosis transmembrane conductance regulator gene by zinc-finger nuclease homology-directed repair. Biores. Open Access 1:99–108, 2012.

    CAS  PubMed Central  PubMed  Google Scholar 

  88. Lee, J. H., et al. Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging. Nat. Med. 13:95–99, 2007.

    CAS  PubMed  Google Scholar 

  89. Lee, J. H., et al. All-in-one target-cell-specific magnetic nanoparticles for simultaneous molecular imaging and siRNA delivery. Angew. Chem. Int. Ed. Engl. 48:4174–4179, 2009.

    CAS  PubMed  Google Scholar 

  90. Lee, J. H., et al. Exchange-coupled magnetic nanoparticles for efficient heat induction. Nat. Nanotechnol. 6:418–422, 2011.

    CAS  PubMed  Google Scholar 

  91. Lewin, M., et al. Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells. Nat. Biotechnol. 18:410–414, 2000.

    CAS  PubMed  Google Scholar 

  92. Li, W., and F. C. Szoka, Jr. Lipid-based nanoparticles for nucleic acid delivery. Pharm. Res. 24:438–449, 2007.

    PubMed  Google Scholar 

  93. Liong, M., et al. Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery. ACS Nano 2:889–896, 2008.

    CAS  PubMed Central  PubMed  Google Scholar 

  94. Mali, P., et al. CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering. Nat. Biotechnol. 31:833–838, 2013.

    Google Scholar 

  95. Mallidi, S., T. Larson, J. Aaron, K. Sokolov, and S. Emelianov. Molecular specific optoacoustic imaging with plasmonic nanoparticles. Opt. Express 15:6583–6588, 2007.

    CAS  PubMed  Google Scholar 

  96. Marraffini, L. A., and E. J. Sontheimer. CRISPR interference: RNA-directed adaptive immunity in bacteria and archaea. Nat. Rev. Genet. 11:181–190, 2010.

    CAS  PubMed Central  PubMed  Google Scholar 

  97. Medarova, Z., W. Pham, C. Farrar, V. Petkova, and A. Moore. In vivo imaging of siRNA delivery and silencing in tumors. Nat. Med. 13:372–377, 2007.

    CAS  PubMed  Google Scholar 

  98. Medintz, I. L., H. T. Uyeda, E. R. Goldman, and H. Mattoussi. Quantum dot bioconjugates for imaging, labelling and sensing. Nat. Mater. 4:435–446, 2005.

    CAS  PubMed  Google Scholar 

  99. Medintz, I. L., et al. Proteolytic activity monitored by fluorescence resonance energy transfer through quantum-dot-peptide conjugates. Nat. Mater. 5:581–589, 2006.

    CAS  PubMed  Google Scholar 

  100. Miller, J. C., et al. An improved zinc-finger nuclease architecture for highly specific genome editing. Nat. Biotechnol. 25:778–785, 2007.

    CAS  PubMed  Google Scholar 

  101. Montet, X., K. Montet-Abou, F. Reynolds, R. Weissleder, and L. Josephson. Nanoparticle imaging of integrins on tumor cells. Neoplasia 8:214–222, 2006.

    CAS  PubMed Central  PubMed  Google Scholar 

  102. Moscou, M. J., and A. J. Bogdanove. A simple cipher governs DNA recognition by TAL effectors. Science 326:1501, 2009.

    CAS  PubMed  Google Scholar 

  103. Mussolino, C., et al. A novel TALE nuclease scaffold enables high genome editing activity in combination with low toxicity. Nucleic Acids Res. 39:9283–9293, 2011.

    CAS  PubMed Central  PubMed  Google Scholar 

  104. Nahrendorf, M., et al. Noninvasive vascular cell adhesion molecule-1 imaging identifies inflammatory activation of cells in atherosclerosis. Circulation 114:1504–1511, 2006.

    CAS  PubMed  Google Scholar 

  105. Namiki, Y., et al. A novel magnetic crystal-lipid nanostructure for magnetically guided in vivo gene delivery. Nat. Nanotechnol. 4:598–606, 2009.

    CAS  PubMed  Google Scholar 

  106. Nie, S. M., X. Yun, J. K. Gloria, and J. W. Simmons. Nanotechnology applications in cancer. Annu. Rev. Biomed. Eng. 9:257–288, 2007.

    CAS  PubMed  Google Scholar 

  107. Nitin, N., L. E. LaConte, O. Zurkiya, X. Hu, and G. Bao. Functionalization and peptide-based delivery of magnetic nanoparticles as an intracellular MRI contrast agent. J. Biol. Inorg. Chem. 9:706–712, 2004.

    CAS  PubMed  Google Scholar 

  108. Nobuto, H., et al. Evaluation of systemic chemotherapy with magnetic liposomal doxorubicin and a dipole external electromagnet. Int. J. Cancer 109:627–635, 2004.

    CAS  PubMed  Google Scholar 

  109. Osborn, M. J., et al. TALEN-based gene correction for epidermolysis Bullosa. Mol. Ther. 21:1151–1159, 2013.

    CAS  PubMed  Google Scholar 

  110. Park, J. H., G. von Maltzahn, E. Ruoslahti, S. N. Bhatia, and M. J. Sailor. Micellar hybrid nanoparticles for simultaneous magnetofluorescent imaging and drug delivery. Angew. Chem. Int. Ed. 47:7284–7288, 2008.

    CAS  Google Scholar 

  111. Park, J. H., et al. Magnetic iron oxide nanoworms for tumor targeting and imaging. Adv. Mater. 20:1630–1635, 2008.

    CAS  PubMed Central  PubMed  Google Scholar 

  112. Pellegrino, T., et al. Hydrophobic nanocrystals coated with an amphiphilic polymer shell: a general route to water soluble nanocrystals. Nano Lett. 4:703–707, 2004.

    CAS  Google Scholar 

  113. Perez, J. M., L. Josephson, T. O’Loughlin, D. Hogemann, and R. Weissleder. Magnetic relaxation switches capable of sensing molecular interactions. Nat. Biotechnol. 20:816–820, 2002.

    CAS  PubMed  Google Scholar 

  114. Perez, E. E., J. Wang, J. C. Miller, Y. Jouvenot, K. A. Kim, O. Liu, N. Wang, G. Lee, V. V. Bartsevich, Y. L. Lee, D. Y. Guschin, I. Rupniewski, A. J. Waite, C. Carpenito, R. G. Carroll, J. S. Orange, F. D. Urnov, E. J. Rebar, D. Ando, P. D. Gregory, J. L. Riley, M. C. Holmes, and C. H. June. Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nat. Biotechnol. 26:808–816, 2008.

    CAS  PubMed Central  PubMed  Google Scholar 

  115. Platt, O. S., D. J. Brambilla, W. F. Rosse, P. F. Milner, O. Castro, M. H. Steinberg, and P. P. Klug. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N. Engl. J. Med. 330:1639–1644, 1994.

    CAS  PubMed  Google Scholar 

  116. Popovtzer, R., et al. Targeted gold nanoparticles enable molecular CT imaging of cancer. Nano Lett. 8:4593–4596, 2008.

    CAS  PubMed Central  PubMed  Google Scholar 

  117. Porteus, M. H., and D. Baltimore. Chimeric nucleases stimulate gene targeting in human cells. Science 300:763, 2003.

    PubMed  Google Scholar 

  118. Pridgen, E. M., R. Langer, and O. C. Farokhzad. Biodegradable, polymeric nanoparticle delivery systems for cancer therapy. Nanomedicine (Lond) 2:669–680, 2007.

    CAS  Google Scholar 

  119. Prodan, E., C. Radloff, N. J. Halas, and P. Nordlander. A hybridization model for the plasmon response of complex nanostructures. Science 302:419–422, 2003.

    CAS  PubMed  Google Scholar 

  120. Qian, X., et al. In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags. Nat. Biotechnol. 26:83–90, 2008.

    CAS  PubMed  Google Scholar 

  121. Ramirez, C. L., et al. Engineered zinc finger nickases induce homology-directed repair with reduced mutagenic effects. Nucleic Acids Res. 40:5560–5568, 2012.

    Google Scholar 

  122. Rebar, E. J., and C. O. Pabo. Zinc finger phage: affinity selection of fingers with new DNA-binding specificities. Science 263:671–673, 1994.

    CAS  PubMed  Google Scholar 

  123. Reyon, D., et al. FLASH assembly of TALENs for high-throughput genome editing. Nat. Biotechnol. 30:460–465, 2012.

    CAS  PubMed Central  PubMed  Google Scholar 

  124. Rodríguez-Oliveros, R., and J. A. Sánchez-Gil. Gold nanostars as thermoplasmonic nanoparticles for optical heating. Opt. Express 20:621–626, 2012.

    PubMed  Google Scholar 

  125. Rosensweig, R. E. Heating magnetic fluid with alternating magnetic field. J. Magn. Magn. Mater. 252:370–374, 2002.

    CAS  Google Scholar 

  126. Rouet, P., F. Smih, and M. Jasin. Expression of a site-specific endonuclease stimulates homologous recombination in mammalian cells. Proc. Natl. Acad. Sci. USA 91:6064–6068, 1994.

    CAS  PubMed  Google Scholar 

  127. Sandell, E. B., and H. Õnishi. Photometric Determination of Traces of Metals (4th ed.). New York: Wiley, 1978.

    Google Scholar 

  128. Sander, J. D., et al. Targeted gene disruption in somatic zebrafish cells using engineered TALENs. Nat. Biotechnol. 29:697–698, 2011.

    CAS  PubMed Central  PubMed  Google Scholar 

  129. Santra, S., C. Kaittanis, J. Grimm, and J. M. Perez. Drug/dye-loaded, multifunctional iron oxide nanoparticles for combined targeted cancer therapy and dual optical/magnetic resonance imaging. Small 5:1862–1868, 2009.

    CAS  PubMed Central  PubMed  Google Scholar 

  130. Schmid-Burgk, J. L., T. Schmidt, V. Kaiser, K. Höning, and V. Hornung. A ligation-independent cloning technique for high-throughput assembly of transcription activator-like effector genes. Nat. Biotechnol. 31:76–81, 2013.

    CAS  PubMed  Google Scholar 

  131. Schroeder, A., et al. Treating metastatic cancer with nanotechnology. Nat. Rev. Cancer 12:39–50, 2012.

    CAS  Google Scholar 

  132. Segal, D. J., and J. F. Meckler. Genome engineering at the dawn of the golden age. Annu. Rev. Genomics Hum. Genet. 14:135–158, 2013.

    Google Scholar 

  133. Shin, J. M., et al. Hollow manganese oxide nanoparticles as multifunctional agents for magnetic resonance imaging and drug delivery. Angew. Chem. Int. Ed. 48:321–324, 2009.

    CAS  Google Scholar 

  134. Skrabalak, S. E., L. Au, X. D. Li, and Y. N. Xia. Facile synthesis of Ag nanocubes and Au nanocages. Nat. Protoc. 2:2182–2190, 2007.

    CAS  PubMed  Google Scholar 

  135. Smith, J., et al. Requirements for double-strand cleavage by chimeric restriction enzymes with zinc finger DNA-recognition domains. Nucleic Acids Res. 28:3361–3369, 2000.

    CAS  PubMed Central  PubMed  Google Scholar 

  136. Stanley, S. A., et al. Radio-wave heating of iron oxide nanoparticles can regulate plasma glucose in mice. Science 336:604–608, 2012.

    CAS  PubMed Central  PubMed  Google Scholar 

  137. Streubel, J., C. Blucher, A. Landgraf, and J. Boch. TAL effector RVD specificities and efficiencies. Nat. Biotechnol. 30:593–595, 2012.

    CAS  PubMed  Google Scholar 

  138. Sun, N., J. Liang, Z. Abil, and H. Zhao. Optimized TAL effector nucleases (TALENs) for use in treatment of sickle cell disease. Mol. Biosyst. 8:1255–1263, 2012.

    CAS  PubMed  Google Scholar 

  139. Sun, S., et al. Monodisperse MFe2O4 (M = Fe, Co, Mn) nanoparticles. J. Am. Chem. Soc. 126:273–279, 2004.

    CAS  PubMed  Google Scholar 

  140. Szczepek, M., et al. Structure-based redesign of the dimerization interface reduces the toxicity of zinc-finger nucleases. Nat. Biotechnol. 25:786–793, 2007.

    CAS  PubMed  Google Scholar 

  141. Tang, T., et al. Assessment of inflammatory burden contralateral to the symptomatic carotid stenosis using high-resolution ultrasmall, superparamagnetic iron oxide-enhanced MRI. Stroke J. Cereb. Circ. 37:2266–2270, 2006.

    CAS  Google Scholar 

  142. Thu, M. S., et al. Self-assembling nanocomplexes by combining ferumoxytol, heparin and protamine for cell tracking by magnetic resonance imaging. Nat. Med. 18:463–467, 2012.

    CAS  PubMed Central  PubMed  Google Scholar 

  143. Tong, S., S. Hou, B. Ren, Z. Zheng, and G. Bao. Self-assembly of phospholipid-PEG coating on nanoparticles through dual solvent exchange. Nano Lett. 11:3720–3726, 2011.

    CAS  PubMed Central  PubMed  Google Scholar 

  144. Tong, S., S. J. Hou, Z. L. Zheng, J. Zhou, and G. Bao. Coating optimization of superparamagnetic iron oxide nanoparticles for high T-2 relaxivity. Nano Lett. 10:4607–4613, 2010.

    CAS  PubMed Central  PubMed  Google Scholar 

  145. Tong, S., B. Ren, Z. Zheng, and G. Bao. Tiny grains give huge gains: nanocrystal-based signal amplification for immunosorbent assays. ACS Nano 7:5142–5150, 2013.

    CAS  PubMed  Google Scholar 

  146. Torchilin, V. P., and V. S. Trubetskoy. Which polymers can make nanoparticulate drug carriers long-circulating. Adv. Drug Deliv. Rev. 16:141–155, 1995.

    CAS  Google Scholar 

  147. Tromberg, B. J., et al. Non-invasive in vivo characterization of breast tumors using photon migration spectroscopy. Neoplasia 2:26–40, 2000.

    CAS  PubMed Central  PubMed  Google Scholar 

  148. Tromsdorf, U. I., et al. Size and surface effects on the MRI relaxivity of manganese ferrite nanoparticle contrast agents. Nano Lett. 7:2422–2427, 2007.

    CAS  PubMed  Google Scholar 

  149. Urnov, F. D., et al. Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature 435:646–651, 2005.

    CAS  PubMed  Google Scholar 

  150. Vanweeme, B. K., and A. H. W. Schuurs. Immunoassay using antigen–enzyme conjugates. Febs Lett. 15:232–236, 1971.

    Google Scholar 

  151. von Maltzahn, G., et al. Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas. Cancer Res. 69:3892–3900, 2009.

    PubMed Central  Google Scholar 

  152. Voura, E. B., J. K. Jaiswal, H. Mattoussi, and S. M. Simon. Tracking metastatic tumor cell extravasation with quantum dot nanocrystals and fluorescence emission-scanning microscopy. Nat. Med. 10:993–998, 2004.

    CAS  PubMed  Google Scholar 

  153. Wagner, V., A. Dullaart, A. K. Bock, and A. Zweck. The emerging nanomedicine landscape. Nat. Biotechnol. 24:1211–1217, 2006.

    CAS  PubMed  Google Scholar 

  154. Wang, Y. X., S. M. Hussain, and G. P. Krestin. Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. Eur. Radiol. 11:2319–2331, 2001.

    CAS  PubMed  Google Scholar 

  155. Wang, Y. A., J. J. Li, H. Chen, and X. Peng. Stabilization of inorganic nanocrystals by organic dendrons. J. Am. Chem. Soc. 124:2293–2298, 2002.

    CAS  PubMed  Google Scholar 

  156. Wang, Y., et al. Photoacoustic tomography of a nanoshell contrast agent in the in vivo rat brain. Nano Lett. 4:1689–1692, 2004.

    CAS  Google Scholar 

  157. Weber, E., R. Gruetzner, S. Werner, C. Engler, and S. Marillonnet. Assembly of designer TAL effectors by golden gate cloning. Plos One 6:e19722, 2011.

    CAS  PubMed Central  PubMed  Google Scholar 

  158. Weissleder, R., A. Bogdanov, E. A. Neuwelt, and M. Papisov. Long-circulating iron-oxides for MR imaging. Adv. Drug Deliv. Rev. 16:321–334, 1995.

    CAS  Google Scholar 

  159. Weissleder, R., et al. Superparamagnetic iron oxide: pharmacokinetics and toxicity. AJR Am. J. Roentgenol. 152:167–173, 1989.

    CAS  PubMed  Google Scholar 

  160. Wiedenheft, B., S. H. Sternberg, and J. A. Doudna. RNA-guided genetic silencing systems in bacteria and archaea. Nature 482:331–338, 2012.

    CAS  PubMed  Google Scholar 

  161. Winter, P. M., et al. Molecular imaging of angiogenesis in early-stage atherosclerosis with alpha(v)beta3-integrin-targeted nanoparticles. Circulation 108:2270–2274, 2003.

    CAS  PubMed  Google Scholar 

  162. Wood, A. J., T. W. Lo, B. Zeitler, C. S. Pickle, E. J. Ralston, A. H. Lee, R. Amora, J. C. Miller, E. Leung, X. Meng, L. Zhang, E. J. Rebar, P. D. Gregory, F. D. Urnov, and B. J. Meyer. Targeted genome editing across species using ZFNs and TALENs. Science 333:307, 2011.

    CAS  PubMed Central  PubMed  Google Scholar 

  163. Wu, X., et al. Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots. Nat. Biotechnol. 21:41–46, 2003.

    CAS  PubMed  Google Scholar 

  164. Xiao, A., et al. Chromosomal deletions and inversions mediated by TALENs and CRISPR/Cas in zebrafish. Nucleic Acids Res., 2013. doi:10.1093/nar/gkt464.

  165. Xie, J., J. Huang, X. Li, S. Sun, and X. Chen. Iron oxide nanoparticle platform for biomedical applications. Curr. Med. Chem. 16:1278–1294, 2009.

    CAS  PubMed  Google Scholar 

  166. Xu, Z. C., Y. L. Hou, and S. H. Sun. Magnetic core/shell Fe3O4/Au and Fe3O4/Au/Ag nanoparticles with tunable plasmonic properties. J. Am. Chem. Soc. 129:8698, 2007.

    CAS  PubMed  Google Scholar 

  167. Xu, C. J., and S. H. Sun. Monodisperse magnetic nanoparticles for biomedical applications. Polym. Int. 56:821–826, 2007.

    CAS  Google Scholar 

  168. Xu, C., B. Xing, and J. Rao. A self-assembled quantum dot probe for detecting beta-lactamase activity. Biochem. Biophys. Res. Commun. 344:931–935, 2006.

    CAS  PubMed  Google Scholar 

  169. Yang, X., S. E. Skrabalak, Z. Y. Li, Y. Xia, and L. V. Wang. Photoacoustic tomography of a rat cerebral cortex in vivo with au nanocages as an optical contrast agent. Nano Lett. 7:3798–3802, 2007.

    CAS  PubMed  Google Scholar 

  170. Yang, X., E. W. Stein, S. Ashkenazi, and L. V. Wang. Nanoparticles for photoacoustic imaging. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 1:360–368, 2009.

    CAS  PubMed  Google Scholar 

  171. Yao, H., Y. Zhang, F. Xiao, Z. Xia, and J. Rao. Quantum dot/bioluminescence resonance energy transfer based highly sensitive detection of proteases. Angew. Chem. Int. Ed. 46:4346–4349, 2007.

    CAS  Google Scholar 

  172. Yavuz, M. S., et al. Gold nanocages covered by smart polymers for controlled release with near-infrared light. Nat. Mater. 8:935–939, 2009.

    CAS  PubMed Central  PubMed  Google Scholar 

  173. Yu, W. W., E. Chang, C. M. Sayes, R. Drezek, and V. L. Colvin. Aqueous dispersion of monodisperse magnetic iron oxide nanocrystals through phase transfer. Nanotechnology 17:4483–4487, 2006.

    CAS  Google Scholar 

  174. Yu, W. W., J. C. Falkner, C. T. Yavuz, and V. L. Colvin. Synthesis of monodisperse iron oxide nanocrystals by thermal decomposition of iron carboxylate salts. Chem. Commun. 2306–2307, 2004.

  175. Zharov, V. P., E. N. Galitovskaya, C. Johnson, and T. Kelly. Synergistic enhancement of selective nanophotothermolysis with gold nanoclusters: potential for cancer therapy. Lasers Surg. Med. 37:219–226, 2005.

    PubMed  Google Scholar 

  176. Zhu, M. T., B. Wang, Y. Wang, L. Yuan, H. J. Wang, M. Wang, H. Ouyang, Z. F. Chai, W. Y. Feng, and Y. L. Zhao. Endothelial dysfunction and inflammation induced by iron oxide nanoparticle exposure: Risk factors for early atherosclerosis. Toxicol. Lett. 203:162–171, 2011.

    CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Heart Lung and Blood Institute of the National Institutes of Health (NIH) as a Program of Excellence in Nanotechnology Award (HHSN268201000043C to GB), by an NIH Nanomedicine Development Center Award (PN2 EY018244 to GB), and by the National Science Foundation as a Science and Technology Center Grant (CBET-0939511).

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  1. Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA

    Sheng Tong, Eli J. Fine, Yanni Lin, Thomas J. Cradick & Gang Bao

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Correspondence to Gang Bao.

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Associate Editor Robert Nerem oversaw the review of this article.

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Tong, S., Fine, E.J., Lin, Y. et al. Nanomedicine: Tiny Particles and Machines Give Huge Gains. Ann Biomed Eng 42, 243–259 (2014). https://doi.org/10.1007/s10439-013-0952-x

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