Functionalized quantum dots for biosensing and bioimaging and concerns on toxicity.

Considerable efforts have been devoted to the development of novel functionalized nanomaterials for bio-oriented applications. With unique optical properties and molar scale production, colloidal photoluminescent quantum dots (QDs) have been properly functionalized with controlled interfaces as new class of optical probes with extensive use in biomedical research. In this review, we present a brief summary on the current research interests of using fine engineered QDs as a nanoplatform for biomedical sensing and imaging applications. In addition, recent concerns on the potential toxic effects of QDs are described as a general guidance for the development on QD formulations in future studies.

[1]  M. Swihart,et al.  Preparation of Quantum Dot/Drug Nanoparticle Formulations for Traceable Targeted Delivery and Therapy , 2012, Theranostics.

[2]  Tamitake Itoh,et al.  Reversible dimerization of EGFR revealed by single-molecule fluorescence imaging using quantum dots. , 2010, Chemistry.

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

[4]  Moungi G Bawendi,et al.  A ratiometric CdSe/ZnS nanocrystal pH sensor. , 2006, Journal of the American Chemical Society.

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

[6]  V. Josserand,et al.  Effect of poly(ethylene glycol) length on the in vivo behavior of coated quantum dots. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[7]  A. Alivisatos,et al.  Improved efficiencies in light emitting diodes made with CdSe(CdS) core/shell type nanocrystals and a semiconducting polymer , 1997 .

[8]  Yanbin Li,et al.  Simultaneous detection of Escherichia coli O157:H7 and Salmonella Typhimurium using quantum dots as fluorescence labels. , 2006, The Analyst.

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

[10]  S. Pathak,et al.  Hydroxylated quantum dots as luminescent probes for in situ hybridization. , 2001, Journal of the American Chemical Society.

[11]  T. Pons,et al.  Synthesis and Characterization of Near-Infrared Cu−In−Se/ZnS Core/Shell Quantum Dots for In vivo Imaging , 2010 .

[12]  M. Dahan,et al.  Small and stable peptidic PEGylated quantum dots to target polyhistidine-tagged proteins with controlled stoichiometry. , 2009, Journal of the American Chemical Society.

[13]  Robert Sinclair,et al.  Particle size, surface coating, and PEGylation influence the biodistribution of quantum dots in living mice. , 2008, Small.

[14]  T. Pons,et al.  Comparing intracellular stability and targeting of sulfobetaine quantum dots with other surface chemistries in live cells. , 2012, Small.

[15]  Igor L. Medintz,et al.  Delivering quantum dots into cells: strategies, progress and remaining issues , 2009, Analytical and bioanalytical chemistry.

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

[17]  Yeh-Hsing Lao,et al.  A quantum dot-aptamer beacon using a DNA intercalating dye as the FRET reporter: application to label-free thrombin detection. , 2011, Biosensors & bioelectronics.

[18]  Y. Chai,et al.  Dual signal amplification for highly sensitive electrochemical detection of uropathogens via enzyme-based catalytic target recycling. , 2011, Biosensors & bioelectronics.

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

[20]  Z. Rosenzweig,et al.  Gold nanoparticle-quantum dot-polystyrene microspheres as fluorescence resonance energy transfer probes for bioassays. , 2011, Journal of the American Chemical Society.

[21]  M. Bawendi,et al.  Engineering InAs(x)P(1-x)/InP/ZnSe III-V alloyed core/shell quantum dots for the near-infrared. , 2005, Journal of the American Chemical Society.

[22]  K. Leong,et al.  Simultaneous Non-invasive Analysis of DNA Condensation and Stability by Two-step QD-FRET. , 2009, Nano today.

[23]  Chunhai Fan,et al.  The cytotoxicity of cadmium-based quantum dots. , 2012, Biomaterials.

[24]  Petras Juzenas,et al.  Quantum dots and nanoparticles for photodynamic and radiation therapies of cancer. , 2008, Advanced drug delivery reviews.

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

[26]  A Paul Alivisatos,et al.  Sorting fluorescent nanocrystals with DNA. , 2002, Journal of the American Chemical Society.

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

[28]  Alex Rhee,et al.  Convergence of quantum dot barcodes with microfluidics and signal processing for multiplexed high-throughput infectious disease diagnostics. , 2007, Nano letters.

[29]  Tza-Huei Wang,et al.  Multiplexed hybridization detection with multicolor colocalization of quantum dot nanoprobes. , 2005, Nano letters.

[30]  N. Yao,et al.  High-Quality Manganese-Doped ZnSe Nanocrystals , 2001 .

[31]  Masato Yasuhara,et al.  Physicochemical Properties and Cellular Toxicity of Nanocrystal Quantum Dots Depend on Their Surface Modification , 2004 .

[32]  Igor L. Medintz,et al.  Quantum dots as simultaneous acceptors and donors in time-gated Förster resonance energy transfer relays: characterization and biosensing. , 2012, Journal of the American Chemical Society.

[33]  Hong Ding,et al.  In vivo targeted cancer imaging, sentinel lymph node mapping and multi-channel imaging with biocompatible silicon nanocrystals. , 2011, ACS nano.

[34]  S. Yao,et al.  Label-free fluorescent detection of protein kinase activity based on the aggregation behavior of unmodified quantum dots. , 2011, Analytical chemistry.

[35]  J. Moan,et al.  Generation of Nitrogen Oxide and Oxygen Radicals by Quantum Dots , 2008 .

[36]  Klaas Nicolay,et al.  Magnetic quantum dots for multimodal imaging. , 2009, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[37]  A. Louie,et al.  Synthesis and characterization of manganese-doped silicon nanoparticles: bifunctional paramagnetic-optical nanomaterial. , 2007, Journal of the American Chemical Society.

[38]  Igor L. Medintz,et al.  Two‐Photon Excitation of Quantum‐Dot‐Based Fluorescence Resonance Energy Transfer and Its Applications , 2007 .

[39]  A. Anas,et al.  Photosensitized breakage and damage of DNA by CdSe-ZnS quantum dots. , 2008, The journal of physical chemistry. B.

[40]  Dai Fukumura,et al.  Multistage nanoparticle delivery system for deep penetration into tumor tissue , 2011, Proceedings of the National Academy of Sciences.

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

[42]  Dan Du,et al.  Quantum dot-based immunochromatographic fluorescent biosensor for biomonitoring trichloropyridinol, a biomarker of exposure to chlorpyrifos. , 2010, Analytical chemistry.

[43]  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.

[44]  D. Pang,et al.  Cell-targeting multifunctional nanospheres with both fluorescence and magnetism. , 2005, Small.

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

[46]  Duane E. Prasuhn,et al.  Quantum dot peptide biosensors for monitoring caspase 3 proteolysis and calcium ions. , 2010, ACS nano.

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

[48]  Xiaofei Hu,et al.  Electrochemiluminescence of CdTe quantum dots as labels at nanoporous gold leaf electrodes for ultrasensitive DNA analysis. , 2010, Talanta.

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

[50]  Jackie Y Ying,et al.  Silica-coated nanocomposites of magnetic nanoparticles and quantum dots. , 2005, Journal of the American Chemical Society.

[51]  Sung-jun Han,et al.  In situ visualization of gene expression using polymer-coated quantum-dot-DNA conjugates. , 2009, Small.

[52]  Rui Hu,et al.  A pilot study in non-human primates shows no adverse response to intravenous injection of quantum dots. , 2012, Nature nanotechnology.

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

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

[55]  Chunhai Fan,et al.  The cytotoxicity of CdTe quantum dots and the relative contributions from released cadmium ions and nanoparticle properties. , 2010, Biomaterials.

[56]  Igor L. Medintz,et al.  Quantum dot-based resonance energy transfer and its growing application in biology. , 2009, Physical chemistry chemical physics : PCCP.

[57]  Maxime Dahan,et al.  Velocity, processivity, and individual steps of single myosin V molecules in live cells. , 2009, Biophysical journal.

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

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

[60]  G. Cheon,et al.  Characterization and cancer cell specific binding properties of anti-EGFR antibody conjugated quantum dots. , 2010, Bioconjugate chemistry.

[61]  Hong Xu,et al.  Fluorescent, superparamagnetic nanospheres for drug storage, targeting, and imaging: a multifunctional nanocarrier system for cancer diagnosis and treatment. , 2010, ACS nano.

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

[63]  Jagjit Nanda,et al.  Single-exciton optical gain in semiconductor nanocrystals , 2007, Nature.

[64]  Hyungrak Kim,et al.  Synthesis and characterization of Co/CdSe core/shell nanocomposites: bifunctional magnetic-optical nanocrystals. , 2005, Journal of the American Chemical Society.

[65]  Nancy A Monteiro-Riviere,et al.  Mechanisms of quantum dot nanoparticle cellular uptake. , 2009, Toxicological sciences : an official journal of the Society of Toxicology.

[66]  Wei Chen,et al.  Simultaneous and sensitive determination of multiplex chemical residues based on multicolor quantum dot probes. , 2009, Biosensors & bioelectronics.

[67]  G. Sukhorukov,et al.  Luminescent polymer microcapsules addressable by a magnetic field. , 2004, Langmuir.

[68]  R. Meulenberg,et al.  Magnetic ordering in doped Cd(1-x)Co(x)Se diluted magnetic quantum dots. , 2002, Journal of the American Chemical Society.

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

[70]  Warren C W Chan,et al.  Rapid screening of genetic biomarkers of infectious agents using quantum dot barcodes. , 2011, ACS nano.

[71]  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.

[72]  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.

[73]  D. Slaaf,et al.  Optical and magnetic resonance imaging of cell death and platelet activation using annexin a5-functionalized quantum dots. , 2007, Nano letters.

[74]  Warren C W Chan,et al.  Mediating tumor targeting efficiency of nanoparticles through design. , 2009, Nano letters.

[75]  Miguel A. Correa-Duarte,et al.  Composite Silica Spheres with Magnetic and Luminescent Functionalities , 2006 .

[76]  Igor L. Medintz,et al.  Can luminescent quantum dots be efficient energy acceptors with organic dye donors? , 2005, Journal of the American Chemical Society.

[77]  F. Erogbogbo,et al.  Non-invasive tumor detection in small animals using novel functional Pluronic nanomicelles conjugated with anti-mesothelin antibody. , 2011, Nanoscale.

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

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

[80]  L. Balan,et al.  Folic acid-conjugated core/shell ZnS:Mn/ZnS quantum dots as targeted probes for two photon fluorescence imaging of cancer cells. , 2011, Acta biomaterialia.

[81]  Maung Kyaw Khaing Oo,et al.  Highly sensitive multiplexed heavy metal detection using quantum-dot-labeled DNAzymes. , 2010, ACS nano.

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

[83]  S. Chaudhuri,et al.  Optical and magnetic properties of manganese-incorporated zinc sulfide nanorods synthesized by a solvothermal process. , 2005, The journal of physical chemistry. B.

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

[85]  Igor L. Medintz,et al.  Quantum dot bioconjugates for imaging, labelling and sensing , 2005, Nature materials.

[86]  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.

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

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

[89]  Minghui Yang,et al.  Sensitive electrochemical immunosensor for the detection of cancer biomarker using quantum dot functionalized graphene sheets as labels , 2011 .

[90]  Hong Ding,et al.  Biocompatible near-infrared quantum dots as ultrasensitive probes for long-term in vivo imaging applications. , 2009, Small.

[91]  S. Weiss,et al.  Lighting up individual DNA binding proteins with quantum dots. , 2009, Nano letters.

[92]  Yue-Wern Huang,et al.  Intracellular delivery of quantum dots mediated by a histidine- and arginine-rich HR9 cell-penetrating peptide through the direct membrane translocation mechanism. , 2011, Biomaterials.

[93]  Bing Xu,et al.  Fluorescent magnetic nanocrystals by sequential addition of reagents in a one-pot reaction: a simple preparation for multifunctional nanostructures. , 2007, Journal of the American Chemical Society.

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

[95]  S. Ogale,et al.  Quantum dot bio-conjugate: as a western blot probe for highly sensitive detection of cellular proteins , 2012, Journal of Nanoparticle Research.

[96]  S. Nie,et al.  Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules , 2001, Nature Biotechnology.

[97]  Tetsuro Tanaka,et al.  Tumor targeting based on the effect of enhanced permeability and retention (EPR) and the mechanism of receptor-mediated endocytosis (RME). , 2004, International journal of pharmaceutics.

[98]  Shusheng Zhang,et al.  Versatile electrochemiluminescence assays for cancer cells based on dendrimer/CdSe-ZnS-quantum dot nanoclusters. , 2011, Analytical chemistry.

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

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

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

[102]  S. Gambhir,et al.  A novel clinically translatable fluorescent nanoparticle for targeted molecular imaging of tumors in living subjects. , 2012, Nano letters.

[103]  F. Guillemin,et al.  Visualisation of Sentinel Lymph Node with Indium-Based near Infrared Emitting Quantum Dots in a Murine Metastatic Breast Cancer Model , 2012, PloS one.

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

[105]  Yuesi Wang,et al.  Intracellular oxidative stress and cadmium ions release induce cytotoxicity of unmodified cadmium sulfide quantum dots. , 2009, Toxicology in vitro : an international journal published in association with BIBRA.

[106]  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.

[107]  Angelique Louie,et al.  Multimodality imaging probes: design and challenges. , 2010, Chemical reviews.

[108]  Kevin J. Wilkinson,et al.  Bioaccumulation and effects of CdTe/CdS quantum dots on Chlamydomonas reinhardtii - nanoparticles or the free ions? , 2011, Environmental science & technology.

[109]  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).

[110]  M. O'Connell,et al.  Novel mobilizable prokaryotic two-hybrid system vectors for high-throughput protein interaction mapping in Escherichia coli by bacterial conjugation , 2005, Nucleic acids research.

[111]  Jing-Juan Xu,et al.  Sensitive electrochemiluminescence detection of c-Myc mRNA in breast cancer cells on a wireless bipolar electrode. , 2012, Analytical chemistry.

[112]  Brian R. Long,et al.  Single particle quantum dot imaging achieves ultrasensitive detection capabilities for Western immunoblot analysis. , 2009, ACS nano.

[113]  Gallagher,et al.  Optical properties of manganese-doped nanocrystals of ZnS. , 1994, Physical review letters.

[114]  L. Cohn,et al.  Lymphatic Drainage of the Peritoneal Space: A Pattern Dependent on Bowel Lymphatics , 2007, Annals of Surgical Oncology.