Bioconjugated quantum dots for in vivo molecular and cellular imaging

Advanced Drug Delivery Reviews

Volumn 60, Issue 11, 2008, Pages 1226-1240

  Smith, Andrew M ^a   Duan, Hongwei ^a   Mohs, Aaron M ^a   Nie, Shuming ^a  

^a EMORY UNIVERSITY   (United States)

Author keywords

Biomarkers; Cancer; Cellular imaging; Drug delivery; Fluorescence; Molecular imaging; Nanocrystals; Nanoparticles; Nanotechnology; Quantum dots; Toxicology

Indexed keywords

ABSORPTION; AMINES; ARCHITECTURAL DESIGN; DRUG THERAPY; ELECTRONIC PROPERTIES; EMISSION SPECTROSCOPY; FLUORESCENCE; HEALTH; LIGHT EMISSION; LUMINESCENCE; MOLECULES; NANOPARTICLES; NANOSTRUCTURED MATERIALS; NANOSTRUCTURES; OPTICAL WAVEGUIDES; PHOTOBLEACHING; PIGMENTS; PROTEINS; QUANTUM ELECTRONICS; TISSUE; TUMORS;

(MIN ,MAX ,+) FUNCTIONS; (PL) PROPERTIES; BIOLOGY AND MEDICINE; CELLULAR IMAGING; ELSEVIER (CO); FLUORESCENT LABELING; FLUORESCENT PROTEINS (FP); HIGH AFFINITY; IN VIVO IMAGING; IN-VIVO; LIGHT-EMITTING; MULTI-FUNCTIONAL NANOPARTICLES; NANO SCALING; NANO-METER-SCALE; NANOPARTICLE BIODISTRIBUTION; NEW CLASS; OPTICAL (PET) (OPET); ORGANIC DYES; QUANTUM DOT (CO); QUANTUM DOTS (QDS); SMALL MOLECULES; SPECTRA (CO); SYNTHESIS (OF CHIRAL IONIC LIQUIDS);

SEMICONDUCTOR QUANTUM DOTS;

ANTIBODY; BIOLOGICAL MARKER; CADMIUM; MEMBRANE RECEPTOR; NANOCRYSTAL; NANOPARTICLE; PEPTIDE; QUANTUM DOT; SMALL INTERFERING RNA;

ABSORPTION SPECTROPHOTOMETRY; BINDING AFFINITY; BIOCOMPATIBILITY; BLEACHING; BRIGHTNESS; CANCER CELL; COLLOID; CONJUGATION; CYTOTOXICITY; DRUG DELIVERY SYSTEM; FLUORESCENCE; IN VIVO STUDY; INFRARED RADIATION; LIGHT EMITTING DIODE; MOLECULAR IMAGING; NANOTECHNOLOGY; NANOTOXICOLOGY; NONHUMAN; PHARMACODYNAMICS; PRIORITY JOURNAL; QUANTUM CHEMISTRY; REVIEW; SEMICONDUCTOR; SURFACE PROPERTY; THERMODYNAMICS; TUMOR VASCULARIZATION;

ANIMALS; BIOCOMPATIBLE MATERIALS; DIAGNOSTIC IMAGING; DRUG DELIVERY SYSTEMS; HUMANS; NANOTECHNOLOGY; NEOPLASMS; QUANTUM DOTS; TISSUE DISTRIBUTION;

EID: 46749091612     PISSN: 0169409X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.addr.2008.03.015     Document Type: Review

References (174)

1. Alivisatos A.P. The use of nanocrystals in biological detection. Nat. Biotechnol. 22 (2004) 47-52
2. Ferrari M. Cancer nanotechnology: opportunities and challenges. Nat. Rev. Cancer 5 (2005) 161-171
3. Niemeyer C.M. Nanoparticles, proteins, and nucleic acids: biotechnology meets materials science. Angew. Chem., Int. Ed. 40 (2001) 4128-4158
4. Cao Y.W.C., Jin R.C., and Mirkin C.A. Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection. Science 297 (2002) 1536-1540
5. Gao X.H., Yang L.L., Petros J.A., Marshal F.F., Simons J.W., and Nie S.M. In vivo molecular and cellular imaging with quantum dots. Curr. Opin. Biotechnol. 16 (2005) 63-72
6. Michalet X., Pinaud F.F., Bentolila L.A., Tsay J.M., Doose S., Li J.J., Sundaresan G., Wu A.M., Gambhir S.S., and Weiss S. Quantum dots for live cells, in vivo imaging, and diagnostics. Science 307 (2005) 538-544
7. Nie S.M., Xing Y., Kim G.J., and Simons J.W. Nanotechnology applications in cancer. Annu. Rev. Biomed. Eng. 9 (2007) 257-288
8. Rosi N.L., and Mirkin C.A. Nanostructures in biodiagnostics. Chem. Rev. 105 (2005) 1547-1562
9. Yezhelyev M.V., Gao X., Xing Y., Al-Hajj A., Nie S.M., and O'Regan R.M. Emerging use of nanoparticles in diagnosis and treatment of breast cancer. Lancet Oncol. 7 (2006) 657-667
10. Gao X.H., Cui Y.Y., Levenson R.M., Chung L.W.K., and Nie S.M. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat. Biotechnol. 22 (2004) 969-976
11. Liu Z., Cai W.B., He L.N., Nakayama N., Chen K., Sun X.M., Chen X.Y., and Dai H.J. In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice. Nat. Nanotech. 2 (2007) 47-52
12. Weissleder R., Kelly K., Sun E.Y., Shtatland T., and Josephson L. Cell-specific targeting of nanoparticles by multivalent attachment of small molecules. Nat. Biotechnol. 23 (2005) 1418-1423
13. Lee E.S., Na K., and Bae Y.H. Polymeric micelle for tumor pH and folate-mediated targeting. J. Control. Release 91 (2003) 103-113
14. Hood J.D., Bednarski M., Frausto R., Guccione S., Reisfeld R.A., Xiang R., and Cheresh D.A. Tumor regression by targeted gene delivery to the neovasculature. Science 296 (2002) 2404-2407
15. Duncan R. Polymer conjugates as anticancer nanomedicines. Nat. Rev. Cancer 6 (2006) 688-701
16. Couvreur P., and Vauthier C. Nanotechnology: intelligent design to treat complex disease. Pharm. Res. 23 (2006) 1417-1450
17. Moghimi S.M., Hunter A.C., and Murray J.C. Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol. Rev. 53 (2001) 283-318
18. Torchilin V.P. Micellar nanocarriers: pharmaceutical perspectives. Pharm. Res. 24 (2007) 1-16
19. McCarthy J.R., Kelly K.A., Sun E.Y., and Weissleder R. Targeted delivery of multifunctional magnetic nanoparticles. Nanomedicine 2 (2007) 153-167
20. Harisinghani M.G., Barentsz J., Hahn P.F., Deserno W.M., Tabatabaei S., van de Kaa C.H., de la Rosette J., and Weissleder R. Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N. Engl. J. Med. 348 (2003) 2491-2499
21. Rhyner M.N., Smith A.M., Gao X.H., Mao H., Yang L., and Nie S.M. Quantum dots and multifunctional nanoparticles: new contrast agents for tumor imaging. Nanomedicine 1 (2006) 209-217
22. Xing Y., Chaudry Q., Shen C., Kong K.Y., Zhau H.E., Chung L.W., Petros J.A., O'Regan R.M., Yezhelyev M.V., Simons J.W., Wang M.D., and Nie S.M. Bioconjugated quantum dots for multiplexed and quantitative immunohistochemistry. Nat. Protoc. 2 (2007) 1152-1165
23. Wu X.Y., Liu H.J., Liu J.Q., Haley K.N., Treadway J.A., Larson J.P., Ge N.F., Peale F., and Bruchez M.P. Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots. Nat. Biotechnol. 21 (2003) 41-46
24. Kim S., Lim Y.T., Soltesz E.G., De Grand A.M., Lee J., Nakayama A., Parker J.A., Mihaljevic T., Laurence R.G., Dor D.M., Cohn L.H., Bawendi M.G., and Frangioni J.V. Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nat. Biotechnol. 22 (2004) 93-97
25. Yezhelyev M.V., Al-Hajj A., Morris C., Marcus A.I., Liu T., Lewis M., Cohen C., Zrazhevskiy P., Simons J.W., Rogatko A., Nie S., Gao X., and O'Regan R.M. In situ molecular profiling of breast cancer biomarkers with multicolor quantum dots. Adv. Mater. 19 (2007) 3146-3151
26. Woodle M.C., and Lu P.Y. Nanoparticles deliver RNAi therapy. NanoToday 8 (2005) 34-41
27. Medarova Z., Pham W., Farrar C., Petkova V., and Moore A. In vivo imaging of siRNA delivery and silencing in tumors. Nat. Med. 13 (2007) 372-377
28. Alivisatos A.P. Semiconductor clusters, nanocrystals, and quantum dots. Science 271 (1996) 933-937
29. 1 - xS nanocrystals with highly narrow luminescence spectral width. J. Am. Chem. Soc. 125 (2003) 13559-13563
30. Bailey R.E., and Nie S.M. Alloyed semiconductor quantum dots: tuning the optical properties without changing the particle size. J. Am. Chem. Soc. 125 (2003) 7100-7106
31. Hines M.A., and Scholes G.D. Colloidal PbS nanocrystals with size-tunable near-infrared emission: observation of post-synthesis self-narrowing of the particle size distribution. Adv. Mater. 15 (2003) 1844-1849
32. Kim S., Fisher B., Eisler H.J., and Bawendi M. Type-II quantum dots: CdTe/CdSe(core/shell) and CdSe/ZnTe(core/shell) heterostructures. J. Am. Chem. Soc. 125 (2003) 11466-11467
33. Qu L.H., and Peng X.G. Control of photoluminescence properties of CdSe nanocrystals in growth. J. Am. Chem. Soc. 124 (2002) 2049-2055
34. Pietryga J., Schaller R., Werder D., Stewart M., Klimov V., and Hollingsworth J. Pushing the band gap envelope: mid-infrared emitting colloidal PbSe quantum dots. J. Am. Chem. Soc. 126 (2004) 11752-11753
35. Efros A.L., and Efros A.L. Interband absorption of light in a semiconductor sphere. Sov. Phys. Semicond. 16 (1982) 772-775
36. Ekimov A.I., and Onushchenko A.A. Quantum size effect in the optical-spectra of semiconductor micro-crystals. Sov. Phys. Semicond. 16 (1982) 775-778
37. Crouch D., Norager S., O'Brien P., Park J.H., and Pickett N. New synthetic routes for quantum dots. Philos. Trans. R. Soc. Lond., A 361 (2003) 297-310
38. Bhattacharya P., Ghosh S., and Stiff-Roberts A.D. Quantum dot opto-electronic devices. Annu. Rev. Mater. Res. 34 (2004) 1-40
39. Murray C.B., Norris D.J., and Bawendi M.G. Synthesis and characterization of nearly monodisperse CdE (E = S, Se, Te) semiconductor nanocrystallites. J. Am. Chem. Soc. 115 (1993) 8706-8715
40. Dabbousi B.O., Rodriguez-Viejo J., Mikulec F.V., Heine J.R., Mattoussi H., Ober R., Jensen K.F., and Bawendi M.G. (CdSe)ZnS core-shell quantum dots: synthesis and characterization of a size series of highly luminescent nanocrystallites. J. Phys. Chem. B 101 (1997) 9463-9475
41. Hines M.A., and Guyot-Sionnest P. Synthesis and characterization of strongly luminescing ZnS-capped CdSe nanocrystals. J. Phys. Chem. 100 (1996) 468-471
42. Gerion D., Pinaud F., Williams S.C., Parak W.J., Zanchet D., Weiss S., and Alivisatos A.P. Synthesis and properties of biocompatible water-soluble silica-coated CdSe/ZnS semiconductor quantum dots. J. Phys. Chem. B 105 (2001) 8861-8871
43. Guo W., Li J.J., Wang Y.A., and Peng X.G. Luminescent CdSe/CdS core/shell nanocrystals in dendron boxes: superior chemical, photochemical and thermal stability. J. Am. Chem. Soc. 125 (2003) 3901-3909
44. Bruchez M., Moronne M., Gin P., Weiss S., and Alivisatos A.P. Semiconductor nanocrystals as fluorescent biological labels. Science 281 (1998) 2013-2016
45. Chan W.C.W., and Nie S.M. Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 281 (1998) 2016-2018
46. Talapin D.V., Mekis I., Gotzinger S., Kornowski A., Benson O., and Weller H. CdSe/CdS/ZnS and CdSe/ZnSe/ZnS core-shell-shell nanocrystals. J. Phys. Chem. B 108 (2004) 18826-18831
47. 0.5S/ZnS multishell nanocrystals. J. Am. Chem. Soc. 127 (2005) 7480-7488
48. Gaponik N., Talapin D.V., Rogach A.L., Hoppe K., Shevchenko E.V., Kornowski A., Eychmuller A., and Weller H. Thiol-capping of CdTe nanocrystals: an alternative to organometallic synthetic routes. J. Phys. Chem. B 106 (2002) 7177-7185
49. Dubertret B., Skourides P., Norris D.J., Noireaux V., Brivanlou A.H., and Libchaber A. In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science 298 (2002) 1759-1762
50. Lieleg O., Lopez-Garcia M., Semmrich C., Auernheimer J., Kessler H., and Bausch A.R. Specific integrin labeling in living celts using functionalized nanocrystals. Small 3 (2007) 1560-1565
51. Pathak S., Davidson M.C., and Silva G.A. Characterization of the functional binding properties of antibody conjugated quantum dots. Nano Lett. 7 (2007) 1839-1845
52. Zhang C.Y., Yeh H.C., Kuroki M.T., and Wang T.H. Single-quantum-dot-based DNA nanosensor. Nat. Mater. 4 (2005) 826-831
53. Medintz I.L., Clapp A.R., Mattoussi H., Goldman E.R., Fisher B., and Mauro J.M. Self-assembled nanoscale biosensors based on quantum dot FRET donors. Nat. Mater. 2 (2003) 630-638
54. Tran P.T., Goldman E.R., Anderson G.P., Mauro J.M., and Mattoussi H. Use of luminescent CdSe-ZnS nanocrystal bioconjugates in quantum dot-based nanosensors. Phys. Status Solidi, B 229 (2002) 427-432
55. So M.K., Xu C.J., Loening A.M., Gambhir S.S., and Rao J.H. Self-illuminating quantum dot conjugates for in vivo imaging. Nat. Biotechnol. 24 (2006) 339-343
56. Smith A.M., Duan H.W., Rhyner M.N., Ruan G., and Nie S.M. A systematic examination of surface coatings on the optical and chemical properties of semiconductor quantum dots. Phys. Chem. Chem. Phys. 8 (2006) 3895-3903
57. Xing Y., Smith A.M., Agrawal A., Ruan G., and Nie S.M. Molecular profiling of single cancer cells and clinical tissue specimens with semiconductor quantum dots. Int. J. Nanomedicine 1 (2006) 473-481
58. Lidke D.S., Nagy P., Heintzmann R., Arndt-Jovin D.J., Post J.N., Grecco H.E., Jares-Erijman E.A., and Jovin T.M. Quantum dot ligands provide new insights into erbB/HER receptor-mediated signal transduction. Nat. Biotechnol. 22 (2004) 198-203
59. Bagwe R.P., Zhao X.J., and Tan W.H. Bioconjugated luminescent nanoparticles for biological applications. J. Dispers. Sci. Technol. 24 (2003) 453-464
60. Chen F., and Gerion D. Fluorescent CdSe/ZnS nanocrystal-peptide conjugates for long-term, nontoxic imaging and nuclear targeting in living cells. Nano Lett. 4 (2004) 1827-1832
61. Smith A.M., and Nie S.M. Chemical analysis and cellular imaging with quantum dots. Analyst 129 (2004) 672-677
62. Smith A.M., Dave S., Nie S.M., True L., and Gao X.H. Multicolor quantum dots for molecular diagnostics of cancer. Expert Rev. Mol. Diagn. 6 (2006) 231-244
63. Fountaine T.J., Wincovitch S.M., Geho D.H., Garfield S.H., and Pittaluga S. Multispectral imaging of clinically relevant cellular targets in tonsil and lymphoid tissue using semiconductor quantum dots. Mod. Pathol. 19 (2006) 1181-1191
64. Ferrara D.E., Weiss D., Carnell P.H., Vito R.P., Vega D., Gao X.H., Nie S.M., and Taylor W.R. Quantitative 3D fluorescence technique for the analysis of en face preparations of arterial walls using quantum dot nanocrystals and two-photon excitation laser scanning microscopy. Am. J. Physiol. - Reg. I. 290 (2006) R114-R123
65. Dahan M., Levi S., Luccardini C., Rostaing P., Riveau B., and Triller A. Diffusion dynamics of glycine receptors revealed by single-quantum dot tracking. Science 302 (2003) 442-445
66. Chen H.F., Titushkin I., Stroscio M., and Cho M. Altered membrane dynamics of quantum dot-conjugated integrins during osteogenic differentiation of human bone marrow derived progenitor cells. Biophys. J. 92 (2007) 1399-1408
67. Echarte M.M., Bruno L., Arndt-Jovin D.J., Jovin T.M., and Pietrasanta L.I. Quantitative single particle tracking of NGF-receptor complexes: transport is bidirectional but biased by longer retrograde run lengths. FEBS Lett. 581 (2007) 2905-2913
68. Rajan S.S., and Vu T.Q. Quantum dots monitor TrkA receptor dynamics in the interior of neural PC12 cells. Nano Lett. 6 (2006) 2049-2059
69. Young S.H., and Rozengurt E. Qdot nanocrystal conjugates conjugated to bombesin or ANG II label the cognate G protein-coupled receptor in living cells. Am. J. Physiol., Cell Physiol. 290 (2006) C728-C732
70. Le Gac S., Vermes I., and van den Berg A. Quantum dots based probes conjugated to annexin V for photostable apoptosis detection and imaging. Nano Lett. 6 (2006) 1863-1869
71. Koeppel F., Jaiswal J.K., and Simon S.M. Quantum dot-based sensor for improved detection of apoptotic cells. Nanomedicine 2 (2007) 71-78
72. Jaiswal J.K., Goldman E.R., Mattoussi H., and Simon S.M. Use of quantum dots for live cell imaging. Nat. Methods 1 (2004) 73-78
73. Courty S., Bouzigues C., Luccardini C., Ehrensperger M.V., Bonneau S., and Dahan M. Tracking individual proteins in living cells using single quantum dot imaging. In: Inglese J. (Ed). Methods in Enzymology vol. 414 (2006), Elsevier, Inc., Amsterdam 211-228
74. Howarth M., Takao K., Hayashi Y., and Ting A.Y. Targeting quantum dots to surface proteins in living cells with biotin ligase. Proc. Natl. Acad. Sci. U. S. A. 102 (2005) 7583-7588
75. Bonasio R., Carman C.V., Kim E., Sage P.T., Love K.R., Mempel T.R., Springer T.A., and von Andrian U.H. Specific and covalent labeling of a membrane protein with organic fluorochromes and quantum dots. Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 14753-14758
76. Hanaki K., Momo A., Oku T., Komoto A., Maenosono S., Yamaguchi Y., and Yamamoto K. Semiconductor quantum dot/albumin complex is a long-life and highly photostable endosome marker. Biochem. Biophys. Res. Commun. 302 (2003) 496-501
77. Jaiswal J.K., Mattoussi H., Mauro J.M., and Simon S.M. Long-term multiple color imaging of live cells using quantum dot bioconjugates. Nat. Biotechnol. 21 (2003) 47-51
78. Parak W.J., Boudreau R., Le Gros M., Gerion D., Zanchet D., Micheel C.M., Williams S.C., Alivisatos A.P., and Larabell C. Cell motility and metastatic potential studies based on quantum dot imaging of phagokinetic tracks. Adv. Mater. 14 (2002) 882-885
79. Derfus A.M., Chan W.C.W., and Bhatia S.N. Probing the cytotoxicity of semiconductor quantum dots. Nano Lett. 4 (2004) 11-18
80. Mattheakis L., Dias J., Choi Y., Gong J., Bruchez M., Liu J., and Wang E. Optical coding of mammalian cells using semiconductor quantum dots. Anal. Biochem. 327 (2004) 200-208
81. Lagerholm B., Wang M., Ernst L., Ly D., Liu H., Bruchez M., and Waggoner A. Multicolor coding of cells with cationic peptide coated quantum dots. Nano Lett. 4 (2004) 2019-2022
82. Voura E., Jaiswal J., Mattoussi H., and Simon S. Tracking metastatic tumor cell extravasation with quantum dot nanocrystals and fluorescence emission-scanning microscopy. Nat. Med. 10 (2004) 993-998
83. Derfus A.M., Chan W.C.W., and Bhatia S.N. Intracellular delivery of quantum dots for live cell labeling and organelle tracking. Adv. Mater. 16 (2004) 961-966
84. Courty S., Luccardini C., Bellaiche Y., Cappello G., and Dahan M. Tracking individual kinesin motors in living cells using single quantum-dot imaging. Nano Lett. 6 (2006) 1491-1495
85. Nan X.L., Sims P.A., Chen P., and Xie X.S. Observation of individual microtubule motor steps in living cells with endocytosed quantum dots. J. Phys. Chem. B 109 (2005) 24220-24224
86. Cambi A., Lidke D.S., Arndt-Jovin D.J., Figdor C.G., and Jovin T.M. Ligand-conjugated quantum dots monitor antigen uptake and processing by dendritic cells. Nano Lett. 7 (2007) 970-977
87. Delehanty J.B., Medintz I.L., Pons T., Brunel F.M., Dawson P.E., and Mattoussi H. Self-assembled quantum dot-peptide bioconjugates for selective intracellular delivery. Bioconjug. Chem. 17 (2006) 920-927
88. Langel U. Cell-Penetrating Peptides: Processes and Applications (2002), CRC Press, Boca Raton, FL
89. Brooks H., Lebleu B., and Vives E. Tat peptide-mediated cellular delivery: back to basics. Adv. Drug Deliv. Rev. 57 (2005) 559-577
90. Wadia J.S., and Dowdy S.F. Transmembrane delivery of protein and peptide drugs by TAT-mediated transduction in the treatment of cancer. Adv. Drug Deliv. Rev. 57 (2005) 579-596
91. Gupta B., Levchenko T.S., and Torchilin V.P. Intracellular delivery of large molecules and small particles by cell-penetrating proteins and peptides. Adv. Drug Deliv. Rev. 57 (2005) 637-651
92. Futaki S. Membrane-permeable arginine-rich peptides and the translocation mechanisms. Adv. Drug Deliv. Rev. 57 (2005) 547-558
93. Zorko M., and Langel U. Cell-penetrating peptides: mechanism and kinetics of cargo delivery. Adv. Drug Deliv. Rev. 57 (2005) 529-545
94. Conner S.D., and Schmid S.L. Regulated portals of entry into the cell. Nature 422 (2003) 37-44
95. Ruan G., Agrawal A., Marcus A.I., and Nie S.M. Imaging and tracking of Tat peptide-conjugated quantum dots in living cells: new insights into nanoparticle uptake, intracellular transport, and vesicle shedding. J. Am. Chem. Soc. 129 (2007) 14759-14766
96. Gonczy P., Pichler S., Kirkham M., and Hyman A.A. Cytoplasmic dynein is required for distinct aspects of MTOC positioning, including centrosome separation, in the one cell stage Caenorhabditis elegans embryo. J. Cell Biol. 147 (1999) 135-150
97. Duan H.W., and Nie S.M. Cell-penetrating quantum dots based on multivalent and endosome-disrupting surface coatings. J. Am. Chem. Soc. 129 (2007) 3333-3338
98. Neu M., Fischer D., and Kissel T. Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivatives. J. Gene Med. 7 (2005) 992-1009
99. Boussif O., Lezoualch F., Zanta M.A., Mergny M.D., Scherman D., Demeneix B., and Behr J.P. A versatile vector for gene and oligonucleotide transfer into cells in culture and in-vivo - polyethylenimine. Proc. Natl. Acad. Sci. U. S. A. 92 (1995) 7297-7301
100. Pack D.W., Hoffman A.S., Pun S., and Stayton P.S. Design and development of polymers for gene delivery. Nat. Rev. Drug Discov. 4 (2005) 581-593
101. Lovric J., Bazzi H.S., Cuie Y., Fortin G.R.A., Winnik F.M., and Maysinger D. Differences in subcellular distribution and toxicity of green and red emitting CdTe quantum dots. J. Mol. Med. - JMM 83 (2005) 377-385
102. Nabiev I., Mitchell S., Davies A., Williams Y., Kelleher D., Moore R., Gun'ko Y.K., Byrne S., Rakovich Y.P., Donegan J.F., Sukhanova A., Conroy J., Cottell D., Gaponik N., Rogach A., and Volkov Y. Nonfunctionalized nanocrystals can exploit a cell's active transport machinery delivering them to specific nuclear and cytoplasmic compartments. Nano Lett. 7 (2007) 3452-3461
103. Weissleder R. A clearer vision for in vivo imaging. Nat. Biotechnol. 19 (2001) 316-317
104. Frangioni J.V. In vivo near-infrared fluorescence imaging. Curr. Opin. Chem. Biol. 7 (2003) 626-634
105. Dobrovolskaia M.A., and Mcneil S.E. Immunological properties of engineered nanomaterials. Nat. Nanotech. 2 (2007) 469-478
106. Soltesz E., Kim S., Laurence R., DeGrand A., Parungo C., Dor D., Cohn L., Bawendi M., Frangioni J., and Mihaljevic T. Intraoperative sentinel lymph node mapping of the lung using near-infrared fluorescent quantum dots. Ann. Thorac. Surg. 79 (2005) 269-277
107. Ballou B., Lagerholm B.C., Ernst L.A., Bruchez M.P., and Waggoner A.S. Noninvasive imaging of quantum dots in mice. Bioconjug. Chem. 15 (2004) 79-86
108. Fischer H.C., Liu L.C., Pang K.S., and Chan W.C.W. Pharmacokinetics of nanoscale quantum dots: in vivo distribution, sequestration, and clearance in the rat. Adv. Funct. Mater. 16 (2006) 1299-1305
109. Choi H.S., Liu W., Misra P., Tanaka E., Zimmer J.P., Ipe B.I., Bawendi M.G., and Frangioni J.V. Renal clearance of quantum dots. Nat. Biotechnol. 25 (2007) 1165-1170
110. Zimmer J.P., Kim S.W., Ohnishi S., Tanaka E., Frangioni J.V., and Bawendi M.G. Size series of small indium arsenide-zinc selenide core-shell nanocrystals and their application to in vivo imaging. J. Am. Chem. Soc. 128 (2006) 2526-2527
111. Roberts M., Bentley M., and Harris J. Chemistry for peptide and protein PEGylation. Adv. Drug Deliv. Rev. 54 (2002) 459-476
112. Lee H.A., Imran M., Monteiro-Riviere N.A., Colvin V.L., Yu W.W., and Rivlere J.E. Biodistribution of quantum dot nanoparticles in perfused skin: evidence of coating dependency and periodicity in arterial extraction. Nano Lett. 7 (2007) 2865-2870
113. Jayagopal A., Russ P.K., and Haselton F.R. Surface engineering of quantum dots for in vivo vascular imaging. Bioconjug. Chem. 18 (2007) 1424-1433
114. Larson D.R., Zipfel W.R., Williams R.M., Clark S.W., Bruchez M.P., Wise F.W., and Webb W.W. Water-soluble quantum dots for multiphoton fluorescence imaging in vivo. Science 300 (2003) 1434-1436
115. Rubart M. Two-photon microscopy of cells and tissue. Circ. Res. 95 (2004) 1154-1166
116. Lim Y.T., Kim S., Nakayama A., Stott N.E., Bawendi M.G., and Frangioni J.V. Selection of quantum dot wavelengths for biomedical assays and imaging. Mol. Imaging 2 (2003) 50-64
117. Smith J.D., Fisher G.W., Waggoner A.S., and Campbell P.G. The use of quantum dots for analysis of chick CAM vasculature. Microvasc. Res. 73 (2007) 75-83
118. Parungo C., Colson Y., Kim S., Kim S., Cohn L., Bawendi M., and Frangioni J. Sentinel lymph node mapping of the pleural space. Chest 127 (2005) 1799-1804
119. Parungo C., Ohnishi S., Kim S., Kim S., Laurence R., Soltesz E., Chen F., Colson Y., Cohn L., Bawendi M., and Frangioni J. Intraoperative identification of esophageal sentinel lymph nodes with near-infrared fluorescence imaging. J. Thorac. Cardiovasc. Surg. 129 (2005) 844-850
120. Ballou B., Ernst L.A., Andreko S., Harper T., Fitzpatrick J.A.J., Waggoner A.S., and Bruchez M.P. Sentinel lymph node imaging using quantum dots in mouse tumor models. Bioconjug. Chem. 18 (2007) 389-396
121. Hama Y., Koyama Y., Urano Y., Choyke P.L., and Kobayashi H. 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 (2007) 23-28
122. Kobayashi H., Hama Y., Koyama Y., Barrett T., Regino C.A.S., Urano Y., and Choyke P.L. Simultaneous multicolor imaging of five different lymphatic basins using quantum dots. Nano Lett. 7 (2007) 1711-1716
123. Gopee N.V., Roberts D.W., Webb P., Cozart C.R., Siitonen P.H., Warbritton A.R., Yu W.W., Colvin V.L., Walker N.J., and Howard P.C. Migration of intradermally injected quantum dots to sentinel organs in mice. Toxicol. Sci. 98 (2007) 249-257
124. Hoshino A., Hanaki K., Suzuki K., and Yamamoto K. Applications of T-lymphoma labeled with fluorescent quantum dots to cell tracing markers in mouse body. Biochem. Biophys. Res. Commun. 314 (2004) 46-53
125. Rosen A.B., Kelly D.J., Schuldt A.J.T., Lu J., Potapova I.A., Doronin S.V., Robichaud K.J., Robinson R.B., Rosen M.R., Brink P.R., Gaudette G.R., and Cohen I.S. Finding fluorescent needles in the cardiac haystack: tracking human mesenchymal stem cells labeled with quantum dots for quantitative in vivo three-dimensional fluorescence analysis. Stem Cells 25 (2007) 2128-2138
126. Jain R.K. Delivery of molecular medicine to solid tumors: lessons from in vivo imaging of gene expression and function. J. Control. Release 74 (2001) 7-25
127. Jain R.K. Transport of molecules, particles, and cells in solid tumors. Annu. Rev. Biomed. Eng. 1 (1999) 241-263
128. Maeda H., Wu J., Sawa T., Matsumura Y., and Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J. Control. Release 65 (2000) 271-284
129. Matsumura Y., and Maeda H. A new concept for macromolecular therapeutics in cancer-chemotherapy - mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 46 (1986) 6387-6392
130. Akerman M.E., Chan W.C.W., Laakkonen P., Bhatia S.N., and Ruoslahti E. Nanocrystal targeting in vivo. Proc. Natl. Acad. Sci. U. S. A. 99 (2002) 12617-12621
131. Yu X.F., Chen L.D., Li K.Y., Li Y., Xiao S., Luo X., Liu J., Zhou L., Deng Y.L., Pang D.W., and Wang Q.Q. Immunofluorescence detection with quantum dot bioconjugates for hepatoma in vivo. J. Biomed. Opt. 12 (2007) 014008
132. Cai W.B., Shin D.W., Chen K., Gheysens O., Cao Q.Z., Wang S.X., Gambhir S.S., and Chen X.Y. Peptide-labeled near-infrared quantum dots for imaging tumor vasculature in living subjects. Nano Lett. 6 (2006) 669-676
133. Stroh M., Zimmer J.P., Duda D.G., Levchenko T.S., Cohen K.S., Brown E.B., Scadden D.T., Torchilin V.P., Bawendi M.G., Fukumura D., and Jain R.K. Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo. Nat. Med. 11 (2005) 678-682
134. Tada H., Higuchi H., Wanatabe T.M., and Ohuchi N. In vivo real-time tracking of single quantum dots conjugated with monoclonal anti-HER2 antibody in tumors of mice. Cancer Res. 67 (2007) 1138-1144
135. Yang R.H., Chang L.W., Wu J.P., Tsai M.H., Wang H.J., Kuo Y.C., Yeh T.K., Yang C.S., and Lin P. Persistent tissue kinetics and redistribution of nanoparticles, quantum dot 705, in mice: ICP-MS quantitative assessment. Environ. Health Perspect. 115 (2007) 1339-1343
136. Omarova A., and Phillips C.J.C. A meta-analysis of literature data relating to the relationships between cadmium intake and toxicity indicators in humans. Environ. Res. 103 (2007) 432-440
137. Ikeda M., Watanabe T., Zhang Z.W., Moon C.S., and Shimbo S. The integrity of the liver among people environmentally exposed to cadmium at various levels. Int. Arch. Occup. Environ. Health 69 (1997) 379-385
138. Liu J., Liu Y.P., Michalska A.E., Choo K.H.A., and Klaassen C.D. Distribution and retention of cadmium in metallothionein I and II null mice. Toxicol. Appl. Pharmacol. 136 (1996) 260-268
139. Kirchner C., Liedl T., Kudera S., Pellegrino T., Javier A.M., Gaub H.E., Stolzle S., Fertig N., and Parak W.J. Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles. Nano Lett. 5 (2005) 331-338
140. Cho S.J., Maysinger D., Jain M., Roder B., Hackbarth S., and Winnik F.M. Long-term exposure to CdTe quantum dots causes functional impairments in live cells. Langmuir 23 (2007) 1974-1980
141. Chang E., Thekkek N., Yu W.W., Colvin V.L., and Drezek R. Evaluation of quantum dot cytotoxicity based on intracellular uptake. Small 2 (2006) 1412-1417
142. Maysinger D., Behrendt M., Lalancette-Herbert M., and Kriz J. Real-time imaging of astrocyte response to quantum dots: in vivo screening model system for biocompatibility of nanoparticles. Nano Lett. 7 (2007) 2513-2520
143. Pradhan N., Battaglia D.M., Liu Y.C., and Peng X.G. Efficient, stable, small, and water-soluble doped ZnSe nanocrystal emitters as non-cadmium biomedical labels. Nano Lett. 7 (2007) 312-317
144. Pradhan N., and Peng X.G. Efficient and color-tunable Mn-doped ZnSe nanocrystal emitters: control of optical performance via greener synthetic chemistry. J. Am. Chem. Soc. 129 (2007) 3339-3347
145. Lovric J., Cho S.J., Winnik F.M., and Maysinger D. Unmodified cadmium telluride quantum dots induce reactive oxygen species formation leading to multiple organelle damage and cell death. Chem. Biol. 12 (2005) 1227-1234
146. Aldana J., Wang Y., and Peng X. Photochemical instability of CdSe nanocrystals coated by hydrophilic thiols. J. Am. Chem. Soc. 123 (2001) 8844-8850
147. Zhang T.T., Stilwell J.L., Gerion D., Ding L.H., Elboudwarej O., Cooke P.A., Gray J.W., Alivisatos A.P., and Chen F.F. Cellular effect of high doses of silica-coated quantum dot profiled with high throughput gene expression analysis and high content cellomics measurements. Nano Lett. 6 (2006) 800-808
148. Lam C.W., James J.T., McCluskey R., Arepalli S., and Hunter R.L. A review of carbon nanotube toxicity and assessment of potential occupational and environmental health risks. Crit. Rev. Toxicol. 36 (2006) 189-217
149. Liang J.G., He Z.K., Zhang S.S., Huang S., Ai X.P., Yang H.X., and Han H.Y. Study on DNA damage induced by CdSe quantum dots using nucleic acid molecular "light switches" as probe. Talanta 71 (2007) 1675-1678
150. Green M., and Howman E. Semiconductor quantum dots and free radical induced DNA nicking. Chem. Commun. (2005) 121-123
151. Zhang Y., He J., Wang P.N., Chen J.Y., Lu Z.J., Lu D.R., Guo J., Wang C.C., and Yang W.L. Time-dependent photoluminescence blue shift of the quantum dots in living cells: effect of oxidation by singlet oxygen. J. Am. Chem. Soc. 128 (2006) 13396-13401
152. Ipe B.I., Lehnig M., and Niemeyer C.M. On the generation of free radical species from quantum dots. Small 1 (2005) 706-709
153. Chan W.H., Shiao N.H., and Lu P.Z. CdSe quantum dots induce apoptosis in human neuroblastoma cells via mitochondrial-dependent pathways and inhibition of survival signals. Toxicol. Lett. 167 (2006) 191-200
154. Mulder W.J.M., Koole R., Brandwijk R.J., Storm G., Chin P.T.K., Strijkers G.J., Donega C.D., Nicolay K., and Griffioen A.W. Quantum dots with a paramagnetic coating as a bimodal molecular imaging probe. Nano Lett. 6 (2006) 1-6
155. van Tilborg G.A.F., Mulder W.J.M., Chin P.T.K., Storm G., Reutelingsperger C.P., Nicolay K., and Strijkers G.J. Annexin A5-conjugated quantum dots with a paramagnetic lipidic coating for the multimodal detection of apoptotic cells. Bioconjug. Chem. 17 (2006) 865-868
156. Bakalova R., Zhelev Z., Aoki I., Ohba H., Imai Y., and Kanno I. Silica-shelled single quantum dot micelles as imaging probes with dual or multimodality. Anal. Chem. 78 (2006) 5925-5932
157. Cai W.B., and Chen X. Nanoplatforms for targeted molecular imaging in living subjects. Small 3 (2007) 1840-1854
158. Cai W.B., Chen K., Li Z., Gambhir S.S., and Chen X. Dual-functional probe for PET and near-infrared fluorescence imaging of tumor vasculature. J. Nucl. Med. 48 (2007) 1862-1870
159. Santra S., Yang H.S., Holloway P.H., Stanley J.T., and Mericle R.A. Synthesis of water-dispersible fluorescent, radio-opaque, and paramagnetic CdS : Mn/ZnS quantum dots: a multifunctional probe for bioimaging. J. Am. Chem. Soc. 127 (2005) 1656-1657
160. Wang S., Jarrett B.R., Kauzlarich S.M., and Louie A.Y. Core/shell quantum dots with high relaxivity and photoluminescence for multimodality imaging. J. Am. Chem. Soc. 129 (2007) 3848-3856
161. Gu H.W., Zheng R.K., Zhang X.X., and Xu B. Facile one-pot synthesis of bifunctional heterodimers of nanoparticles: a conjugate of quantum dot and magnetic nanoparticles. J. Am. Chem. Soc. 126 (2004) 5664-5665
162. Gu H.W., Yang Z.M., Gao J.H., Chang C.K., and Xu B. Heterodimers of nanoparticles: formation at a liquid-liquid interface and particle-specific surface modification by functional molecules. J. Am. Chem. Soc. 127 (2005) 34-35
163. Selvan S.T., Patra P.K., Ang C.Y., and Ying J.Y. Synthesis of silica-coated semiconductor and magnetic quantum dots and their use in the imaging of live cells. Angew. Chem., Int. Ed. 46 (2007) 2448-2452
164. Manabe N., Hoshino A., Liang Y.Q., Goto T., Kato N., and Yamamoto K. Quantum dot as a drug tracer in vivo. IEEE T. Nanobiosci. 5 (2006) 263-267
165. Bagalkot V., Zhang L., Levy-Nissenbaum E., Jon S., Kantoff P.W., Langer R., and Farokhzad O.C. Quantum dot-aptamer conjugates for synchronous cancer imaging, therapy, and sensing of drug delivery based on bi-fluorescence resonance energy transfer. Nano Lett. 7 (2007) 3065-3070
166. Chen A.A., Derfus A.M., Khetani S.R., and Bhatia S.N. Quantum dots to monitor RNAi delivery and improve gene silencing. Nucleic Acids Res. 33 (2005) e190
167. Tan W.B., Jiang S., and Zhang Y. Quantum-dot based nanoparticles for targeted silencing of HER2/neu gene via RNA interference. Biomaterials 28 (2007) 1565-1571
168. Kim D.H., and Rossi J.J. Strategies for silencing human disease using RNA interference. Nat. Rev., Genet. 8 (2007) 173-184
169. Rana T.M. Illuminating the silence: understanding the structure and function of small RNAs. Nat. Rev., Mol. Cell Biol. 8 (2007) 23-36
170. Bumcrot D., Manoharan M., Koteliansky V., and Sah D.W.Y. RNAi therapeutics: a potential new class of pharmaceutical drugs. Nat. Chem. Biol. 2 (2006) 711-719
171. Meister G., and Tuschl T. Mechanisms of gene silencing by double-stranded RNA. Nature 431 (2004) 343-349
172. Dykxhoorn D.M., and Lieberman J. The silent revolution: RNA interference as basic biology, research tool, and therapeutic. Annu. Rev. Med. 56 (2005) 401-423
173. Derfus A.M., Chen A.A., Min D.H., Ruoslahti E., and Bhatia S.N. Targeted quantum dot conjugates for siRNA delivery. Bioconjug. Chem. 18 (2007) 1391-1396
174. X.H. Gao, M.V. Yezhelyev, L. Qi, R.M. O'Regan, S.M. Nie, Proton-sponge-coated quantum dots for siRNA delivery and imaging, J. Am. Chem. Soc. 130 (in press).