Bioconjugated quantum dots for in vivo molecular and cellular imaging.

Semiconductor quantum dots (QDs) are tiny light-emitting particles on the nanometer scale, and are emerging as a new class of fluorescent labels for biology and medicine. In comparison with organic dyes and fluorescent proteins, they have unique optical and electronic properties, with size-tunable light emission, superior signal brightness, resistance to photobleaching, and broad absorption spectra for simultaneous excitation of multiple fluorescence colors. QDs also provide a versatile nanoscale scaffold for designing multifunctional nanoparticles with both imaging and therapeutic functions. When linked with targeting ligands such as antibodies, peptides or small molecules, QDs can be used to target tumor biomarkers as well as tumor vasculatures with high affinity and specificity. Here we discuss the synthesis and development of state-of-the-art QD probes and their use for molecular and cellular imaging. We also examine key issues for in vivo imaging and therapy, such as nanoparticle biodistribution, pharmacokinetics, and toxicology.

[1]  Klaas Nicolay,et al.  Quantum dots with a paramagnetic coating as a bimodal molecular imaging probe. , 2006, Nano letters.

[2]  I. Kanno,et al.  Silica-shelled single quantum dot micelles as imaging probes with dual or multimodality. , 2006, Analytical chemistry.

[3]  John V Frangioni,et al.  Size series of small indium arsenide-zinc selenide core-shell nanocrystals and their application to in vivo imaging. , 2006, Journal of the American Chemical Society.

[4]  Shuming Nie,et al.  Bioconjugated quantum dots for multiplexed and quantitative immunohistochemistry , 2007, Nature Protocols.

[5]  Shuming Nie,et al.  Proton-sponge coated quantum dots for siRNA delivery and intracellular imaging. , 2008, Journal of the American Chemical Society.

[6]  W. Webb,et al.  Water-Soluble Quantum Dots for Multiphoton Fluorescence Imaging in Vivo , 2003, Science.

[7]  S. Gambhir,et al.  Quantum Dots for Live Cells, in Vivo Imaging, and Diagnostics , 2005, Science.

[8]  Hans C. Fischer,et al.  Pharmacokinetics of Nanoscale Quantum Dots: In Vivo Distribution, Sequestration, and Clearance in the Rat , 2006 .

[9]  Daniel W. Pack,et al.  Design and development of polymers for gene delivery , 2005, Nature Reviews Drug Discovery.

[10]  R. Weissleder,et al.  Cell-specific targeting of nanoparticles by multivalent attachment of small molecules , 2005, Nature Biotechnology.

[11]  Vladimir P Torchilin,et al.  Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo , 2005, Nature Medicine.

[12]  Xiaolin Nan,et al.  Observation of individual microtubule motor steps in living cells with endocytosed quantum dots. , 2005, The journal of physical chemistry. B.

[13]  L. Cohn,et al.  Intraoperative identification of esophageal sentinel lymph nodes with near-infrared fluorescence imaging. , 2005, The Journal of thoracic and cardiovascular surgery.

[14]  C. Phillips,et al.  A meta-analysis of literature data relating to the relationships between cadmium intake and toxicity indicators in humans. , 2007, Environmental research.

[15]  J. Jaiswal,et al.  Quantum dot-based sensor for improved detection of apoptotic cells. , 2007, Nanomedicine.

[16]  L. Cohn,et al.  Sentinel lymph node mapping of the pleural space. , 2005, Chest.

[17]  Igor Nabiev,et al.  Nonfunctionalized nanocrystals can exploit a cell's active transport machinery delivering them to specific nuclear and cytoplasmic compartments. , 2007, Nano letters.

[18]  Christine M. Micheel,et al.  Cell Motility and Metastatic Potential Studies Based on Quantum Dot Imaging of Phagokinetic Tracks , 2002 .

[19]  P. Guyot-Sionnest,et al.  Synthesis and Characterization of Strongly Luminescing ZnS-Capped CdSe Nanocrystals , 1996 .

[20]  M. Ikeda,et al.  The integrity of the liver among people environmentally exposed to cadmium at various levels , 1997, International archives of occupational and environmental health.

[21]  E. Vivés,et al.  Tat peptide-mediated cellular delivery: back to basics. , 2005, Advanced drug delivery reviews.

[22]  S. Nie,et al.  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. , 2006, American journal of physiology. Regulatory, integrative and comparative physiology.

[23]  T. Vu,et al.  Quantum dots monitor TrkA receptor dynamics in the interior of neural PC12 cells. , 2006, Nano letters.

[24]  Byron Ballou,et al.  Noninvasive imaging of quantum dots in mice. , 2004, Bioconjugate chemistry.

[25]  S. Nie,et al.  Molecular profiling of single cancer cells and clinical tissue specimens with semiconductor quantum dots , 2006, International journal of nanomedicine.

[26]  V. Torchilin,et al.  Micellar Nanocarriers: Pharmaceutical Perspectives , 2006, Pharmaceutical Research.

[27]  Sanjiv S Gambhir,et al.  Peptide-labeled near-infrared quantum dots for imaging tumor vasculature in living subjects. , 2006, Nano letters.

[28]  Horst Kessler,et al.  Specific integrin labeling in living cells using functionalized nanocrystals. , 2007, Small.

[29]  M. Bruchez,et al.  Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots , 2003, Nature Biotechnology.

[30]  Vincent Noireaux,et al.  In Vivo Imaging of Quantum Dots Encapsulated in Phospholipid Micelles , 2002, Science.

[31]  P. Jain,et al.  (CdSe)ZnS Core−Shell Quantum Dots: Synthesis and Characterization of a Size Series of Highly Luminescent Nanocrystallites , 2009 .

[32]  John J. Rossi,et al.  Strategies for silencing human disease using RNA interference , 2007, Nature Reviews Genetics.

[33]  M. Dobrovolskaia,et al.  Immunological properties of engineered nanomaterials , 2007, Nature Nanotechnology.

[34]  Xiaogang Peng,et al.  Luminescent CdSe/CdS core/shell nanocrystals in dendron boxes: superior chemical, photochemical and thermal stability. , 2003, Journal of the American Chemical Society.

[35]  A. I. Ekimov,et al.  Quantum size effect in semiconductor microcrystals , 1985 .

[36]  M. Manoharan,et al.  RNAi therapeutics: a potential new class of pharmaceutical drugs , 2006, Nature chemical biology.

[37]  H. Mattoussi,et al.  Use of quantum dots for live cell imaging , 2004, Nature Methods.

[38]  S. Bhatia,et al.  Probing the Cytotoxicity Of Semiconductor Quantum Dots. , 2004, Nano letters.

[39]  Swadeshmukul Santra,et al.  Synthesis of water-dispersible fluorescent, radio-opaque, and paramagnetic CdS:Mn/ZnS quantum dots: a multifunctional probe for bioimaging. , 2005, Journal of the American Chemical Society.

[40]  J. Frangioni In vivo near-infrared fluorescence imaging. , 2003, Current opinion in chemical biology.

[41]  Siddhartha Ghosh,et al.  QUANTUM DOT OPTO-ELECTRONIC DEVICES , 2004 .

[42]  M. Bawendi,et al.  Renal clearance of quantum dots , 2007, Nature Biotechnology.

[43]  Igor L. Medintz,et al.  Self-assembled quantum dot-peptide bioconjugates for selective intracellular delivery. , 2006, Bioconjugate chemistry.

[44]  Sangeeta N. Bhatia,et al.  The European charter for counteracting obesity: A late but important step towards action. Observations on the WHO-Europe ministerial conference, Istanbul, November 15–17, 2006 , 2007, The international journal of behavioral nutrition and physical activity.

[45]  F. Marshall,et al.  In vivo molecular and cellular imaging with quantum dots. , 2005, Current opinion in biotechnology.

[46]  Jennifer A Hollingsworth,et al.  Pushing the band gap envelope: mid-infrared emitting colloidal PbSe quantum dots. , 2004, Journal of the American Chemical Society.

[47]  Daniele Gerion,et al.  Fluorescent CdSe/ZnS nanocrystal-peptide conjugates for long-term, nontoxic imaging and , 2004 .

[48]  Sanjiv S. Gambhir,et al.  Dual-Function Probe for PET and Near-Infrared Fluorescence Imaging of Tumor Vasculature , 2007, Journal of Nuclear Medicine.

[49]  Xiaogang Peng,et al.  Control of photoluminescence properties of CdSe nanocrystals in growth. , 2002, Journal of the American Chemical Society.

[50]  Phil G Campbell,et al.  The use of quantum dots for analysis of chick CAM vasculature. , 2007, Microvascular research.

[51]  Xiaogang Peng,et al.  Photochemical instability of CdSe nanocrystals coated by hydrophilic thiols. , 2001, Journal of the American Chemical Society.

[52]  D. Fischer,et al.  Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivatives , 2005, The journal of gene medicine.

[53]  T. Jovin,et al.  Quantitative single particle tracking of NGF–receptor complexes: Transport is bidirectional but biased by longer retrograde run lengths , 2007, FEBS letters.

[54]  C. Niemeyer REVIEW Nanoparticles, Proteins, and Nucleic Acids: Biotechnology Meets Materials Science , 2022 .

[55]  T. Rana,et al.  Illuminating the silence: understanding the structure and function of small RNAs , 2007, Nature Reviews Molecular Cell Biology.

[56]  M. Rubart,et al.  Two-photon microscopy of cells and tissue. , 2004, Circulation research.

[57]  Bing Xu,et al.  Facile one-pot synthesis of bifunctional heterodimers of nanoparticles: a conjugate of quantum dot and magnetic nanoparticles. , 2004, Journal of the American Chemical Society.

[58]  P. Couvreur,et al.  Nanotechnology: Intelligent Design to Treat Complex Disease , 2006, Pharmaceutical Research.

[59]  H. Maeda,et al.  A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. , 1986, Cancer research.

[60]  M. Woodle,et al.  Nanoparticles deliver RNAi therapy , 2005 .

[61]  Y. Liu,et al.  Distribution and retention of cadmium in metallothionein I and II null mice. , 1996, Toxicology and applied pharmacology.

[62]  Chad A. Mirkin,et al.  Nanostructures in Biodiagnostics , 2005 .

[63]  Wolfgang Knoll,et al.  Alloyed Zn(x)Cd(1-x)S nanocrystals with highly narrow luminescence spectral width. , 2003, Journal of the American Chemical Society.

[64]  M. Bawendi,et al.  Synthesis and characterization of nearly monodisperse CdE (E = sulfur, selenium, tellurium) semiconductor nanocrystallites , 1993 .

[65]  Hanxi Yang,et al.  Study on DNA damage induced by CdSe quantum dots using nucleic acid molecular "light switches" as probe. , 2007, Talanta.

[66]  Yohanns Bellaiche,et al.  Tracking individual kinesin motors in living cells using single quantum-dot imaging. , 2006, Nano letters.

[67]  Gabriel A Silva,et al.  Characterization of the functional binding properties of antibody conjugated quantum dots. , 2007, Nano letters.

[68]  M. Stroscio,et al.  Altered membrane dynamics of quantum dot-conjugated integrins during osteogenic differentiation of human bone marrow derived progenitor cells. , 2007, Biophysical journal.

[69]  R. Weissleder,et al.  Targeted delivery of multifunctional magnetic nanoparticles. , 2007, Nanomedicine.

[70]  C. Figdor,et al.  Ligand-conjugated quantum dots monitor antigen uptake and processing by dendritic cells. , 2007, Nano letters.

[71]  Ulo Langel,et al.  Cell-penetrating peptides: mechanism and kinetics of cargo delivery. , 2005, Advanced drug delivery reviews.

[72]  S. Nie,et al.  Chemical analysis and cellular imaging with quantum dots. , 2004, The Analyst.

[73]  S. Pittaluga,et al.  Multispectral imaging of clinically relevant cellular targets in tonsil and lymphoid tissue using semiconductor quantum dots , 2006, Modern Pathology.

[74]  M. Bawendi,et al.  Type-II quantum dots: CdTe/CdSe(core/shell) and CdSe/ZnTe(core/shell) heterostructures. , 2003, Journal of the American Chemical Society.

[75]  Gregory D. Scholes,et al.  Colloidal PbS Nanocrystals with Size‐Tunable Near‐Infrared Emission: Observation of Post‐Synthesis Self‐Narrowing of the Particle Size Distribution , 2003 .

[76]  Jia He,et al.  Time-dependent photoluminescence blue shift of the quantum dots in living cells: effect of oxidation by singlet oxygen. , 2006, Journal of the American Chemical Society.

[77]  Shuming Nie,et al.  Cell-penetrating quantum dots based on multivalent and endosome-disrupting surface coatings. , 2007, Journal of the American Chemical Society.

[78]  T. Mihaljevic,et al.  Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping , 2004, Nature Biotechnology.

[79]  N. Pradhan,et al.  Efficient, stable, small, and water-soluble doped ZnSe nanocrystal emitters as non-cadmium biomedical labels. , 2007, Nano letters.

[80]  M. Howarth,et al.  Targeting quantum dots to surface proteins in living cells with biotin ligase. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[81]  Sandra L. Schmid,et al.  Regulated portals of entry into the cell , 2003, Nature.

[82]  Shan Jiang,et al.  Quantum-dot based nanoparticles for targeted silencing of HER2/neu gene via RNA interference. , 2007, Biomaterials.

[83]  Kaiyang Li,et al.  Immunofluorescence detection with quantum dot bioconjugates for hepatoma in vivo. , 2007, Journal of biomedical optics.

[84]  P. O’Brien,et al.  New synthetic routes for quantum dots , 2003, Philosophical Transactions of the Royal Society of London. Series A: Mathematical, Physical and Engineering Sciences.

[85]  Akiyoshi Hoshino,et al.  Applications of T-lymphoma labeled with fluorescent quantum dots to cell tracing markers in mouse body. , 2004, Biochemical and biophysical research communications.

[86]  J. James,et al.  A Review of Carbon Nanotube Toxicity and Assessment of Potential Occupational and Environmental Health Risks , 2006, Critical reviews in toxicology.

[87]  J. Post,et al.  Quantum dot ligands provide new insights into erbB/HER receptor–mediated signal transduction , 2004, Nature Biotechnology.

[88]  J. Matthew Mauro,et al.  Long-term multiple color imaging of live cells using quantum dot bioconjugates , 2003, Nature Biotechnology.

[89]  H. Yeh,et al.  Single-quantum-dot-based DNA nanosensor , 2005, Nature materials.

[90]  Phan T. Tran,et al.  Use of Luminescent CdSe–ZnS Nanocrystal Bioconjugates in Quantum Dot‐Based Nanosensors , 2002 .

[91]  Shimon Weiss,et al.  Synthesis and Properties of Biocompatible Water-Soluble Silica-Coated CdSe/ZnS Semiconductor Quantum Dots† , 2001 .

[92]  R. Weissleder A clearer vision for in vivo imaging , 2001, Nature Biotechnology.

[93]  M. Rosen,et al.  Finding Fluorescent Needles in the Cardiac Haystack: Tracking Human Mesenchymal Stem Cells Labeled with Quantum Dots for Quantitative In Vivo Three‐Dimensional Fluorescence Analysis , 2007, Stem cells.

[94]  Ming-Hsien Tsai,et al.  Persistent Tissue Kinetics and Redistribution of Nanoparticles, Quantum Dot 705, in Mice: ICP-MS Quantitative Assessment , 2007, Environmental health perspectives.

[95]  Yong Taik Lim,et al.  Selection of Quantum Dot Wavelengths for Biomedical Assays and Imaging , 2003, Molecular imaging.

[96]  P. Alivisatos The use of nanocrystals in biological detection , 2004, Nature Biotechnology.

[97]  Hassan S. Bazzi,et al.  Differences in subcellular distribution and toxicity of green and red emitting CdTe quantum dots , 2005, Journal of Molecular Medicine.

[98]  Frederick R Haselton,et al.  Surface engineering of quantum dots for in vivo vascular imaging. , 2007, Bioconjugate chemistry.

[99]  Angelique Y. Louie,et al.  Core/shell quantum dots with high relaxivity and photoluminescence for multimodality imaging. , 2007 .

[100]  N. Manabe,et al.  Quantum Dot as a Drug Tracer In Vivo , 2006, IEEE Transactions on NanoBioscience.

[101]  D. Maysinger,et al.  Real-time imaging of astrocyte response to quantum dots: in vivo screening model system for biocompatibility of nanoparticles. , 2007, Nano letters.

[102]  Christof M Niemeyer,et al.  On the generation of free radical species from quantum dots. , 2005, Small.

[103]  Nigel J Walker,et al.  Migration of intradermally injected quantum dots to sentinel organs in mice. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[104]  S. Nie,et al.  In vivo cancer targeting and imaging with semiconductor quantum dots , 2004, Nature Biotechnology.

[105]  S. Nie,et al.  Nanotechnology applications in cancer. , 2007, Annual review of biomedical engineering.

[106]  Tim Liedl,et al.  Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles. , 2005, Nano letters.

[107]  Igor L. Medintz,et al.  Self-assembled nanoscale biosensors based on quantum dot FRET donors , 2003, Nature materials.

[108]  M. Ferrari Cancer nanotechnology: opportunities and challenges , 2005, Nature Reviews Cancer.

[109]  S. Futaki Membrane-permeable arginine-rich peptides and the translocation mechanisms. , 2005, Advanced drug delivery reviews.

[110]  Mark Green,et al.  Semiconductor quantum dots and free radical induced DNA nicking. , 2005, Chemical communications.

[111]  Sung Ju Cho,et al.  Unmodified cadmium telluride quantum dots induce reactive oxygen species formation leading to multiple organelle damage and cell death. , 2005, Chemistry & biology.

[112]  Tristan Barrett,et al.  Simultaneous multicolor imaging of five different lymphatic basins using quantum dots. , 2007, Nano letters.

[113]  James A J Fitzpatrick,et al.  Sentinel lymph node imaging using quantum dots in mouse tumor models. , 2007, Bioconjugate chemistry.

[114]  Shuming Nie,et al.  Emerging use of nanoparticles in diagnosis and treatment of breast cancer. , 2006, The Lancet. Oncology.

[115]  C. Mirkin,et al.  Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection. , 2002, Science.

[116]  Jim E Riviere,et al.  Biodistribution of quantum dot nanoparticles in perfused skin: evidence of coating dependency and periodicity in arterial extraction. , 2007, Nano letters.

[117]  S M Moghimi,et al.  Long-circulating and target-specific nanoparticles: theory to practice. , 2001, Pharmacological reviews.

[118]  M. Bentley,et al.  Chemistry for peptide and protein PEGylation. , 2002, Advanced drug delivery reviews.

[119]  Anna Moore,et al.  In vivo imaging of siRNA delivery and silencing in tumors , 2007, Nature Medicine.

[120]  J. Lieberman,et al.  THE SILENT REVOLUTION : RNA Interference as Basic Biology , Research Tool , and Therapeutic , 2010 .

[121]  Ruth Duncan,et al.  Polymer conjugates as anticancer nanomedicines , 2006, Nature Reviews Cancer.

[122]  H. Dai,et al.  In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice. , 2020, Nature nanotechnology.

[123]  Shuming Nie,et al.  In Situ Molecular Profiling of Breast Cancer Biomarkers with Multicolor Quantum Dots , 2007 .

[124]  S. Nie,et al.  Quantum dot bioconjugates for ultrasensitive nonisotopic detection. , 1998, Science.

[125]  Wen-Hsiung Chan,et al.  CdSe quantum dots induce apoptosis in human neuroblastoma cells via mitochondrial-dependent pathways and inhibition of survival signals. , 2006, Toxicology letters.

[126]  A Paul Alivisatos,et al.  Cellular effect of high doses of silica-coated quantum dot profiled with high throughput gene expression analysis and high content cellomics measurements. , 2006, Nano letters.

[127]  Andreas Kornowski,et al.  CdSe/CdS/ZnS and CdSe/ZnSe/ZnS Core−Shell−Shell Nanocrystals , 2004 .

[128]  Klaas Nicolay,et al.  Annexin A5-conjugated quantum dots with a paramagnetic lipidic coating for the multimodal detection of apoptotic cells. , 2006, Bioconjugate chemistry.

[129]  S. Colowick,et al.  Methods in Enzymology , Vol , 1966 .

[130]  Albert van den Berg,et al.  Quantum dots based probes conjugated to annexin V for photostable apoptosis detection and imaging. , 2006, Nano letters.

[131]  John V Frangioni,et al.  Intraoperative sentinel lymph node mapping of the lung using near-infrared fluorescent quantum dots. , 2005, The Annals of thoracic surgery.

[132]  Christopher B. Murray,et al.  Synthesis and characterization of nearly monodisperse CdE (E = S, Se, Te) semiconductor nanocrystallites , 2005 .

[133]  Erkki Ruoslahti,et al.  Nanocrystal targeting in vivo , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[134]  Alf Mews,et al.  Synthesis and characterization of highly luminescent CdSe-core CdS/Zn0.5Cd0.5S/ZnS multishell nanocrystals. , 2005, Journal of the American Chemical Society.

[135]  Philippe Rostaing,et al.  Diffusion Dynamics of Glycine Receptors Revealed by Single-Quantum Dot Tracking , 2003, Science.

[136]  J. Ying,et al.  Synthesis of silica-coated semiconductor and magnetic quantum dots and their use in the imaging of live cells. , 2007, Angewandte Chemie.

[137]  D. Ly,et al.  Multicolor Coding of Cells with Cationic Peptide Coated Quantum Dots , 2004 .

[138]  Hedi Mattoussi,et al.  Tracking metastatic tumor cell extravasation with quantum dot nanocrystals and fluorescence emission-scanning microscopy , 2004, Nature Medicine.

[139]  Robert Langer,et al.  Quantum dot-aptamer conjugates for synchronous cancer imaging, therapy, and sensing of drug delivery based on bi-fluorescence resonance energy transfer. , 2007, Nano letters.

[140]  Weibo Cai,et al.  Nanoplatforms for targeted molecular imaging in living subjects. , 2007, Small.

[141]  Kenji Yamamoto,et al.  Semiconductor quantum dot/albumin complex is a long-life and highly photostable endosome marker. , 2003, Biochemical and biophysical research communications.

[142]  Sanjiv S Gambhir,et al.  Self-illuminating quantum dot conjugates for in vivo imaging , 2006, Nature Biotechnology.

[143]  M. Bruchez,et al.  Optical coding of mammalian cells using semiconductor quantum dots. , 2004, Analytical biochemistry.

[144]  Maxime Dahan,et al.  Tracking individual proteins in living cells using single quantum dot imaging. , 2006, Methods in enzymology.

[145]  R K Jain,et al.  Delivery of molecular medicine to solid tumors: lessons from in vivo imaging of gene expression and function. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[146]  Steffen Hackbarth,et al.  Long-term exposure to CdTe quantum dots causes functional impairments in live cells. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[147]  S. H. Young,et al.  Qdot nanocrystal conjugates conjugated to bombesin or ANG II label the cognate G protein-coupled receptor in living cells. , 2006, American journal of physiology. Cell physiology.

[148]  N. Pradhan,et al.  Efficient and color-tunable Mn-doped ZnSe nanocrystal emitters: control of optical performance via greener synthetic chemistry. , 2007, Journal of the American Chemical Society.

[149]  H. Maeda,et al.  Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[150]  P. Choyke,et al.  Simultaneous two-color spectral fluorescence lymphangiography with near infrared quantum dots to map two lymphatic flows from the breast and the upper extremity , 2007, Breast Cancer Research and Treatment.

[151]  Enoch Kim,et al.  Specific and covalent labeling of a membrane protein with organic fluorochromes and quantum dots , 2007, Proceedings of the National Academy of Sciences.

[152]  Shuming Nie,et al.  Multicolor quantum dots for molecular diagnostics of cancer , 2006, Expert review of molecular diagnostics.

[153]  Erkki Ruoslahti,et al.  Targeted quantum dot conjugates for siRNA delivery. , 2007, Bioconjugate chemistry.

[154]  A. Alivisatos Semiconductor Clusters, Nanocrystals, and Quantum Dots , 1996, Science.

[155]  Ülo Langel,et al.  Cell-Penetrating Peptides : Processes and Applications , 2002 .

[156]  Noriaki Ohuchi,et al.  In vivo real-time tracking of single quantum dots conjugated with monoclonal anti-HER2 antibody in tumors of mice. , 2007, Cancer research.

[157]  A. Marcus,et al.  Imaging and tracking of tat peptide-conjugated quantum dots in living cells: new insights into nanoparticle uptake, intracellular transport, and vesicle shedding. , 2007, Journal of the American Chemical Society.

[158]  Weihong Tan,et al.  Bioconjugated Luminescent Nanoparticles for Biological Applications , 2003 .

[159]  Bing Xu,et al.  Heterodimers of nanoparticles: formation at a liquid-liquid interface and particle-specific surface modification by functional molecules. , 2005, Journal of the American Chemical Society.

[160]  Alexander L. Efros,et al.  Interband absorption of light in a semiconductor sphere , 2005 .

[161]  Sangeeta N. Bhatia,et al.  Intracellular Delivery of Quantum Dots for Live Cell Labeling and Organelle Tracking , 2004 .

[162]  D. Balding,et al.  HLA Sequence Polymorphism and the Origin of Humans , 2006 .

[163]  D. Scherman,et al.  A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[164]  You Han Bae,et al.  Polymeric micelle for tumor pH and folate-mediated targeting. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[165]  Shuming Nie,et al.  Quantum dots and multifunctional nanoparticles: new contrast agents for tumor imaging. , 2006, Nanomedicine.

[166]  S. Nie,et al.  A systematic examination of surface coatings on the optical and chemical properties of semiconductor quantum dots. , 2006, Physical chemistry chemical physics : PCCP.

[167]  Rebekah Drezek,et al.  Evaluation of quantum dot cytotoxicity based on intracellular uptake. , 2006, Small.

[168]  R K Jain,et al.  Transport of molecules, particles, and cells in solid tumors. , 1999, Annual review of biomedical engineering.

[169]  T. Tuschl,et al.  Mechanisms of gene silencing by double-stranded RNA , 2004, Nature.

[170]  Ralph Weissleder,et al.  Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. , 2003, The New England journal of medicine.

[171]  Steven F Dowdy,et al.  Transmembrane delivery of protein and peptide drugs by TAT-mediated transduction in the treatment of cancer. , 2005, Advanced drug delivery reviews.

[172]  M. Bednarski,et al.  Tumor Regression by Targeted Gene Delivery to the Neovasculature , 2002, Science.

[173]  Nikolai Gaponik,et al.  THIOL-CAPPING OF CDTE NANOCRYSTALS: AN ALTERNATIVE TO ORGANOMETALLIC SYNTHETIC ROUTES , 2002 .

[174]  Shuming Nie,et al.  Alloyed semiconductor quantum dots: tuning the optical properties without changing the particle size. , 2003, Journal of the American Chemical Society.

[175]  Robert Langer,et al.  Quantum dot-aptamer conjugates for synchronous cancer imaging and therapy based on bi-fluorescence resonance energy transfer , 2007 .

[176]  P. Gönczy,et al.  Cytoplasmic Dynein Is Required for Distinct Aspects of Mtoc Positioning, Including Centrosome Separation, in the One Cell Stage Caenorhabditis elegans Embryo , 1999, The Journal of cell biology.

[177]  Vladimir P Torchilin,et al.  Intracellular delivery of large molecules and small particles by cell-penetrating proteins and peptides. , 2005, Advanced drug delivery reviews.