Multifunctional Quantum Dots for Personalized Medicine.

Successes in biomedical research and state-of-the-art medicine have undoubtedly improved the quality of life. However, a number of diseases, such as cancer, immunodeficiencies, and neurological disorders, still evade conventional diagnostic and therapeutic approaches. A transformation towards personalized medicine may help to combat these diseases. For this, identification of disease molecular fingerprints and their association with prognosis and targeted therapy must become available. Quantum dots (QDs), semiconductor nanocrystals with unique photo-physical properties, represent a novel class of fluorescence probes to address many of the needs of personalized medicine. This review outlines the properties of QDs that make them a suitable platform for advancing personalized medicine, examines several proof-of-concept studies showing utility of QDs for clinically relevant applications, and discusses current challenges in introducing QDs into clinical practice.

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

[2]  Tadashi Nagashima,et al.  Three-dimensional Imaging of the Intracellular Localization of Growth Hormone and Prolactin and Their mRNA Using Nanocrystal (Quantum Dot) and Confocal Laser Scanning Microscopy Techniques , 2005, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[3]  Yasushi Hiraoka,et al.  Multispectral imaging fluorescence microscopy for living cells. , 2002, Cell structure and function.

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

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

[6]  R. Nitschke,et al.  Quantum dots versus organic dyes as fluorescent labels , 2008, Nature Methods.

[7]  M. Haswell-Elkins,et al.  Safe levels of cadmium intake to prevent renal toxicity in human subjects. , 2000, The British journal of nutrition.

[8]  M Laird Forrest,et al.  Effects of nanomaterial physicochemical properties on in vivo toxicity. , 2009, Advanced drug delivery reviews.

[9]  K. Ritchie,et al.  Design of quantum dot-conjugated lipids for long-term, high-speed tracking experiments on cell surfaces. , 2008, Journal of the American Chemical Society.

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

[11]  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.

[12]  Ron C. Hardman.  A Toxicologic Review of Quantum Dots: Toxicity Depends on Physicochemical and Environmental Factors , 2005, Environmental health perspectives.

[13]  L. Hurst,et al.  Hearing silence: non-neutral evolution at synonymous sites in mammals , 2006, Nature Reviews Genetics.

[14]  Xinguo Jiang,et al.  Quantum dots bearing lectin-functionalized nanoparticles as a platform for in vivo brain imaging. , 2008, Bioconjugate chemistry.

[15]  Jeunghoon Lee,et al.  Labeling and intracellular tracking of functionally active plasmid DNA with semiconductor quantum dots. , 2006, Molecular therapy : the journal of the American Society of Gene Therapy.

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

[17]  L. True,et al.  Quantum dots for molecular pathology: their time has arrived. , 2007, The Journal of molecular diagnostics : JMD.

[18]  A. Alivisatos.  Perspectives on the Physical Chemistry of Semiconductor Nanocrystals , 1996 .

[19]  W. Law,et al.  Aqueous-phase synthesis of highly luminescent CdTe/ZnTe core/shell quantum dots optimized for targeted bioimaging. , 2009, Small.

[20]  K. Roth,et al.  Combined Tyramide Signal Amplification and Quantum Dots for Sensitive and Photostable Immunofluorescence Detection , 2003, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

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

[22]  John J Spinelli,et al.  HER-2/neu in Breast Cancer: Interobserver Variability and Performance of Immunohistochemistry with 4 Antibodies Compared with Fluorescent In Situ Hybridization , 2001, Modern Pathology.

[23]  David L. Schwartz,et al.  Imaging Epidermal Growth Factor Receptor Expression In vivo: Pharmacokinetic and Biodistribution Characterization of a Bioconjugated Quantum Dot Nanoprobe , 2008, Clinical Cancer Research.

[24]  Xiaohu Gao,et al.  Quantum dot-amphipol nanocomplex for intracellular delivery and real-time imaging of siRNA. , 2008, ACS nano.

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

[26]  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.

[27]  Yong Wang,et al.  Cell type–specific delivery of siRNAs with aptamer-siRNA chimeras , 2006, Nature Biotechnology.

[28]  N. Kotov,et al.  In vitro toxicity testing of nanoparticles in 3D cell culture. , 2009, Small.

[29]  E. Petricoin,et al.  Nanotechnology in clinical proteomics. , 2007, Nanomedicine.

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

[31]  U. Banin,et al.  Structural and spectroscopic investigations of CdS/HgS/CdS quantum-dot quantum wells. , 1996, Physical review. B, Condensed matter.

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

[33]  Liang Li,et al.  Highly Luminescent CuInS2/ZnS Core/Shell Nanocrystals: Cadmium-Free Quantum Dots for In Vivo Imaging , 2009 .

[34]  Chava Kimchi-Sarfaty,et al.  Silent polymorphisms speak: how they affect pharmacogenomics and the treatment of cancer. , 2007, Cancer research.

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

[36]  Warren C. W. Chan,et al.  Quantum Dots in Biological and Biomedical Research: Recent Progress and Present Challenges , 2006 .

[37]  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.

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

[39]  Betty Y. S. Kim,et al.  Biodegradable quantum dot nanocomposites enable live cell labeling and imaging of cytoplasmic targets. , 2008, Nano letters.

[40]  M. Bawendi,et al.  Selection of Quantum Dot Wavelengths for Biomedical Assays and Imaging , 2003, Molecular Imaging.

[41]  S. Nie,et al.  Quantum Dot Nanocrystals for In Vivo Molecular and Cellular Imaging¶ , 2004 .

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

[43]  L. True,et al.  Quantitative immunohistochemistry: a new tool for surgical pathology? , 1988, American journal of clinical pathology.

[44]  Graham Dellaire,et al.  Application of Quantum Dots as Probes for Correlative Fluorescence, Conventional, and Energy-filtered Transmission Electron Microscopy , 2004, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[45]  N. Monteiro-Riviere,et al.  Limitations and relative utility of screening assays to assess engineered nanoparticle toxicity in a human cell line. , 2009, Toxicology and applied pharmacology.

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

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

[48]  Peter E Barker,et al.  Semiconductor nanocrystal probes for human metaphase chromosomes. , 2004, Nucleic acids research.

[49]  D. Leslie-Pelecky,et al.  Iron oxide nanoparticles for sustained delivery of anticancer agents. , 2005, Molecular pharmaceutics.

[50]  Xiaohu Gao,et al.  Emerging application of quantum dots for drug delivery and therapy , 2008 .

[51]  B. Cui,et al.  One at a time, live tracking of NGF axonal transport using quantum dots , 2007, Proceedings of the National Academy of Sciences.

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

[53]  K K Jain,et al.  Personalised medicine for cancer: from drug development into clinical practice , 2005, Expert opinion on pharmacotherapy.

[54]  H. Dai,et al.  PEG branched polymer for functionalization of nanomaterials with ultralong blood circulation. , 2009, Journal of the American Chemical Society.

[55]  D. Price,et al.  Quantum dot semiconductor nanocrystals for immunophenotyping by polychromatic flow cytometry , 2006, Nature Medicine.

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

[57]  C. Tsang,et al.  Water‐Soluble Silicon Quantum Dots with Wavelength‐Tunable Photoluminescence , 2009 .

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

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

[60]  Xingyu Li,et al.  Intracellular delivery of quantum dots tagged antisense oligodeoxynucleotides by functionalized multiwalled carbon nanotubes. , 2007, Nano letters.

[61]  Raymond P. Molloy,et al.  In vivo multiphoton microscopy of deep brain tissue. , 2004, Journal of neurophysiology.

[62]  M. Dahan,et al.  High-affinity labeling and tracking of individual histidine-tagged proteins in live cells using Ni2+ tris-nitrilotriacetic acid quantum dot conjugates. , 2009, Nano letters (Print).

[63]  C. Larabell,et al.  Quantum dots as cellular probes. , 2005, Annual review of biomedical engineering.

[64]  Ning Wang,et al.  Mechanochemical delivery and dynamic tracking of fluorescent quantum dots in the cytoplasm and nucleus of living cells. , 2009, Nano letters.

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

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

[67]  K. Zedeler,et al.  Inter- and intraobserver variability in the histopathological diagnosis of medullary carcinoma of the breast, and its prognostic implications , 1989, Breast Cancer Research and Treatment.

[68]  Glenn Walter,et al.  Rapid and effective labeling of brain tissue using TAT-conjugated CdS:Mn/ZnS quantum dots. , 2005, Chemical communications.

[69]  R. Tsien,et al.  The Dynamic Control of Kiss-And-Run and Vesicular Reuse Probed with Single Nanoparticles , 2009, Science.

[70]  Thomas J Deerinck,et al.  Correlated light and electron microscopic imaging of multiple endogenous proteins using Quantum dots , 2005, Nature Methods.

[71]  Xiaogang Peng,et al.  High Quality ZnSe and ZnS Nanocrystals Formed by Activating Zinc Carboxylate Precursors , 2004 .

[72]  Tony Yuen,et al.  Method for multiplex cellular detection of mRNAs using quantum dot fluorescent in situ hybridization , 2005, Nucleic acids research.

[73]  S. Nie,et al.  Luminescent quantum dots for multiplexed biological detection and imaging. , 2002, Current opinion in biotechnology.

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

[75]  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.

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

[77]  S. Nie,et al.  Molecular profiling of single cells and tissue specimens with quantum dots. , 2003, Trends in biotechnology.

[78]  Shuming Nie,et al.  Oxidative quenching and degradation of polymer-encapsulated quantum dots: new insights into the long-term fate and toxicity of nanocrystals in vivo. , 2008, Journal of the American Chemical Society.

[79]  Huiguang Zhu,et al.  Quantum dot weathering results in microbial toxicity. , 2008, Environmental science & technology.

[80]  F Tokumasu,et al.  Development and application of quantum dots for immunocytochemistry of human erythrocytes , 2003, Journal of microscopy.

[81]  David Twomey,et al.  Imaging of multiple mRNA targets using quantum dot based in situ hybridization and spectral deconvolution in clinical biopsies. , 2006, Biochemical and biophysical research communications.

[82]  Hong Ding,et al.  Imaging pancreatic cancer using bioconjugated InP quantum dots. , 2009, ACS nano.

[83]  Arezou A Ghazani,et al.  High throughput quantification of protein expression of cancer antigens in tissue microarray using quantum dot nanocrystals. , 2006, Nano letters.

[84]  Sangjin Park,et al.  Carbon nanosyringe array as a platform for intracellular delivery. , 2009, Nano letters.

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

[86]  Michael J Sailor,et al.  Biodegradable luminescent porous silicon nanoparticles for in vivo applications. , 2009, Nature materials.

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