Overview of Stabilizing Ligands for Biocompatible Quantum Dot Nanocrystals

Luminescent colloidal quantum dots (QDs) possess numerous advantages as fluorophores in biological applications. However, a principal challenge is how to retain the desirable optical properties of quantum dots in aqueous media while maintaining biocompatibility. Because QD photophysical properties are directly related to surface states, it is critical to control the surface chemistry that renders QDs biocompatible while maintaining electronic passivation. For more than a decade, investigators have used diverse strategies for altering the QD surface. This review summarizes the most successful approaches for preparing biocompatible QDs using various chemical ligands.

[1]  Andreas Kornowski,et al.  Dynamic distribution of growth rates within the ensembles of colloidal II-VI and III-V semiconductor nanocrystals as a factor governing their photoluminescence efficiency. , 2002, Journal of the American Chemical Society.

[2]  X. Lou,et al.  Surface Modification of CdSe and CdSe/ZnS Semiconductor Nanocrystals with Poly(N,N-dimethylaminoethyl methacrylate) , 2006 .

[3]  Z. Rosenzweig,et al.  Luminescent CdSe Quantum Dot Doped Stabilized Micelles , 2002 .

[4]  Chia-Chun Chen,et al.  Self-Assembly of Monolayers of Cadmium Selenide Nanocrystals with Dual Color Emission , 1999 .

[5]  Hao Yan,et al.  A facile one-step in situ functionalization of quantum dots with preserved photoluminescence for bioconjugation. , 2007, Journal of the American Chemical Society.

[6]  Shuming Nie,et al.  Minimizing the hydrodynamic size of quantum dots with multifunctional multidentate polymer ligands. , 2008, Journal of the American Chemical Society.

[7]  A. Sutherland,et al.  Quantum dots as luminescent probes in biological systems , 2002 .

[8]  A. Miyawaki Visualization of the spatial and temporal dynamics of intracellular signaling. , 2003, Developmental cell.

[9]  Michel De Waard,et al.  Compact and highly stable quantum dots through optimized aqueous phase transfer , 2011, BiOS.

[10]  T. A. Hatton,et al.  Bilayer Surfactant Stabilized Magnetic Fluids: Synthesis and Interactions at Interfaces , 1999 .

[11]  Bernhardt L Trout,et al.  Modified ligand-exchange for efficient solubilization of CdSe/ZnS quantum dots in water: a procedure guided by computational studies. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[12]  A. R. Clapp,et al.  Dithiocarbamates as capping ligands for water-soluble quantum dots. , 2010, ACS applied materials & interfaces.

[13]  D. Wright,et al.  Monoclonal Antibody Recognition of Histidine-Rich Peptide Encapsulated Nanoclusters , 2002 .

[14]  E. Wang,et al.  One-pot synthesis of CdTe nanocrystals and shape control of luminescent CdTe-cystine nanocomposites. , 2006, Small.

[15]  C. Bustamante,et al.  Conjugation of DNA to Silanized Colloidal Semiconductor Nanocrystalline Quantum Dots , 2002 .

[16]  F. Mizukami,et al.  Highly Luminescent Flexible Quantum Dot–Clay Films , 2008 .

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

[18]  T. Livache,et al.  Biotinylated CdSe/ZnSe nanocrystals for specific fluorescent labeling , 2004 .

[19]  Igor L. Medintz,et al.  Quantum-dot/dopamine bioconjugates function as redox coupled assemblies for in vitro and intracellular pH sensing. , 2010, Nature materials.

[20]  A. Rogach,et al.  Colloidally Prepared CdHgTe and HgTe Quantum Dots with Strong Near‐Infrared Luminescence , 2001 .

[21]  A. Nozik Quantum dot solar cells , 2002 .

[22]  G. Scholes,et al.  Surface passivation of luminescent colloidal quantum dots with poly(dimethylaminoethyl methacrylate) through a ligand exchange process. , 2004, Journal of the American Chemical Society.

[23]  M. S. Thakur,et al.  Photoabsorption and resonance energy transfer phenomenon in CdTe-protein bioconjugates: an insight into QD-biomolecular interactions. , 2011, Bioconjugate chemistry.

[24]  Hedi Mattoussi,et al.  Capping of CdSe–ZnS quantum dots with DHLA and subsequent conjugation with proteins , 2006, Nature Protocols.

[25]  Igor L. Medintz,et al.  Potential clinical applications of quantum dots , 2008, International journal of nanomedicine.

[26]  Supramolecular control of complexation-induced fluorescence change of water-soluble, beta-cyclodextrin-modified CdS quantum dots. , 2004, Chemical communications.

[27]  Igor L. Medintz,et al.  Quantum-dot-based multiplexed fluorescence resonance energy transfer , 2005, SPIE BiOS.

[28]  Igor L. Medintz,et al.  Hydrodynamic dimensions, electrophoretic mobility, and stability of hydrophilic quantum dots. , 2006, The journal of physical chemistry. B.

[29]  J. Ying,et al.  Synthesis and Cell‐Imaging Applications of Glutathione‐Capped CdTe Quantum Dots , 2007 .

[30]  Katsuyuki Nobusada,et al.  Glutathione-protected gold clusters revisited: bridging the gap between gold(I)-thiolate complexes and thiolate-protected gold nanocrystals. , 2005, Journal of the American Chemical Society.

[31]  Thomas Nann,et al.  Single quantum dots in spherical silica particles. , 2004, Angewandte Chemie.

[32]  Igor Nabiev,et al.  Highly Stable Fluorescent Nanocrystals as a Novel Class of Labels for Immunohistochemical Analysis of Paraffin-Embedded Tissue Sections , 2002, Laboratory Investigation.

[33]  J. Matthew Mauro,et al.  Self-Assembly of CdSe−ZnS Quantum Dot Bioconjugates Using an Engineered Recombinant Protein , 2000 .

[34]  Shimon Weiss,et al.  Bioactivation and cell targeting of semiconductor CdSe/ZnS nanocrystals with phytochelatin-related peptides. , 2004, Journal of the American Chemical Society.

[35]  A Paul Alivisatos,et al.  Semiconductor quantum rods as single molecule fluorescent biological labels. , 2007, Nano letters.

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

[37]  A. Pron,et al.  Chelating ligands for nanocrystals' surface functionalization. , 2004, Journal of the American Chemical Society.

[38]  R. Advíncula,et al.  Conjugated Oligothiophene-Dendron-Capped CdSe Nanoparticles: Synthesis and Energy Transfer , 2004 .

[39]  P. K. Mandal,et al.  A simple and versatile route to stable quantum dot-dye hybrids in nonaqueous and aqueous solutions. , 2008, Journal of the American Chemical Society.

[40]  P. Seeberger,et al.  In vitro imaging and in vivo liver targeting with carbohydrate capped quantum dots. , 2009, Journal of the American Chemical Society.

[41]  T. Vlugt,et al.  Adsorption and Binding of Ligands to CdSe Nanocrystals , 2009 .

[42]  P. Snee,et al.  Water-soluble semiconductor nanocrystals cap exchanged with metalated ligands. , 2011, ACS nano.

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

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

[45]  Xiaogang Peng,et al.  Stabilization of inorganic nanocrystals by organic dendrons. , 2002, Journal of the American Chemical Society.

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

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

[48]  Jagjit Nanda,et al.  Effect of the thiol-thiolate equilibrium on the photophysical properties of aqueous CdSe/ZnS nanocrystal quantum dots. , 2005, Journal of the American Chemical Society.

[49]  Igor L. Medintz,et al.  Modification of Poly(ethylene glycol)-Capped Quantum Dots with Nickel Nitrilotriacetic Acid and Self-Assembly with Histidine-Tagged Proteins , 2010 .

[50]  T. Nann,et al.  Single Quantum Dots in Silica Spheres by Microemulsion Synthesis , 2005 .

[51]  Xiaogang Peng,et al.  Size-dependent dissociation pH of thiolate ligands from cadmium chalcogenide nanocrystals. , 2005, Journal of the American Chemical Society.

[52]  Huifeng Qian,et al.  Facile one-pot synthesis of luminescent, water-soluble, and biocompatible glutathione-coated CdTe nanocrystals. , 2006, Small.

[53]  Jung Ho Yu,et al.  Magnetic fluorescent delivery vehicle using uniform mesoporous silica spheres embedded with monodisperse magnetic and semiconductor nanocrystals. , 2006, Journal of the American Chemical Society.

[54]  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.

[55]  Vaidyanathan Subramanian,et al.  Quantum dot solar cells. harvesting light energy with CdSe nanocrystals molecularly linked to mesoscopic TiO2 films. , 2006, Journal of the American Chemical Society.

[56]  G Ulrich Nienhaus,et al.  Zwitterionic biocompatible quantum dots for wide pH stability and weak nonspecific binding to cells. , 2009, ACS nano.

[57]  Chad A. Mirkin,et al.  Programmed Assembly of DNA Functionalized Quantum Dots , 1999 .

[58]  Joachim O. Rädler,et al.  Hydrophobic Nanocrystals Coated with an Amphiphilic Polymer Shell: A General Route to Water Soluble Nanocrystals , 2004 .

[59]  H. Mattoussi,et al.  Multifunctional ligands based on dihydrolipoic acid and polyethylene glycol to promote biocompatibility of quantum dots , 2009, Nature Protocols.

[60]  E. Doris,et al.  A versatile strategy for quantum dot ligand exchange. , 2007, Journal of the American Chemical Society.

[61]  Hans C. Fischer,et al.  Design and characterization of lysine cross-linked mercapto-acid biocompatible quantum dots , 2006 .

[62]  M. Sastry,et al.  Phase Transfer of Aqueous Gold Colloidal Particles Capped with Inclusion Complexes of Cyclodextrin and Alkanethiol Molecules into Chloroform , 2001 .

[63]  M. Sastry,et al.  Formation of Water-Dispersible Gold Nanoparticles Using a Technique Based on Surface-Bound Interdigitated Bilayers , 2003 .

[64]  Horst Weller,et al.  Photochemistry of colloidal semiconductors. 20. Surface modification and stability of strong luminescing CdS particles , 1987 .

[65]  Igor L. Medintz,et al.  Multidentate poly(ethylene glycol) ligands provide colloidal stability to semiconductor and metallic nanocrystals in extreme conditions. , 2010, Journal of the American Chemical Society.

[66]  Igor L. Medintz,et al.  Enhancing the stability and biological functionalities of quantum dots via compact multifunctional ligands. , 2007, Journal of the American Chemical Society.

[67]  R. Demadrille,et al.  Carbodithioate-Containing Oligo- and Polythiophenes for Nanocrystals' Surface Functionalization , 2006 .

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

[69]  N. Felorzabihi,et al.  Water-Soluble CdSe Quantum Dots Passivated by a Multidentate Diblock Copolymer , 2007 .

[70]  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.

[71]  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.

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

[73]  Christine M. Micheel,et al.  Biological applications of colloidal nanocrystals , 2003 .

[74]  Hong Yang,et al.  “Pulling” Nanoparticles into Water: Phase Transfer of Oleic Acid Stabilized Monodisperse Nanoparticles into Aqueous Solutions of α-Cyclodextrin , 2003 .

[75]  G. Müller,et al.  Adjustment of the Band Gap Energies of Biostabilized CdS Nanoparticles by Application of Statistical Design of Experiments , 2004 .

[76]  Masanori Ando,et al.  Highly Luminescent Water-Soluble InP/ZnS Nanocrystals Prepared via Reactive Phase Transfer and Photochemical Processing , 2008 .

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

[78]  Igor Nabiev,et al.  Biocompatible fluorescent nanocrystals for immunolabeling of membrane proteins and cells. , 2004, Analytical biochemistry.

[79]  Rebekah Drezek,et al.  Forming biocompatible and nonaggregated nanocrystals in water using amphiphilic polymers. , 2007, Journal of the American Chemical Society.

[80]  A. Surolia,et al.  Sugar-quantum dot conjugates for a selective and sensitive detection of lectins. , 2007, Bioconjugate chemistry.

[81]  M. Bawendi,et al.  Compact cysteine-coated CdSe(ZnCdS) quantum dots for in vivo applications. , 2007, Journal of the American Chemical Society.

[82]  Moungi G Bawendi,et al.  Oligomeric ligands for luminescent and stable nanocrystal quantum dots. , 2003, Journal of the American Chemical Society.

[83]  T. Emrick,et al.  The use of 4-substituted pyridines to afford amphiphilic, pegylated cadmium selenide nanoparticles. , 2003, Chemical communications.

[84]  Y. Qian,et al.  InP nanocrystals via surfactant-aided hydrothermal synthesis , 2004 .

[85]  Xiaohu Gao,et al.  Silica-polymer dual layer-encapsulated quantum dots with remarkable stability. , 2010, ACS nano.

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

[87]  G. Nienhaus,et al.  Quenching of CdSe-ZnS Core-Shell Quantum Dot Luminescence by Water-Soluble Thiolated Ligands , 2007 .

[88]  G. Konstantatos,et al.  Solution-processed PbS quantum dot infrared photodetectors and photovoltaics , 2005, Nature materials.

[89]  Brad A. Kairdolf,et al.  Minimizing nonspecific cellular binding of quantum dots with hydroxyl-derivatized surface coatings. , 2008, Analytical chemistry.

[90]  J. Hainfeld,et al.  Ni-NTA-gold clusters target His-tagged proteins. , 1999, Journal of structural biology.

[91]  H. Vogel,et al.  Highly fluorescent streptavidin-coated CdSe nanoparticles: preparation in water, characterization, and micropatterning. , 2004, Langmuir : the ACS journal of surfaces and colloids.

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

[93]  Xiaogang Peng,et al.  Highly luminescent, stable, and water-soluble CdSe/CdS core-shell dendron nanocrystals with carboxylate anchoring groups. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[94]  Jianghong Rao,et al.  Quantum dot bioconjugates for in vitro diagnostics & in vivo imaging. , 2008, Cancer biomarkers : section A of Disease markers.

[95]  Mingyuan Gao,et al.  Enhancement Effect of Illumination on the Photoluminescence of Water-Soluble CdTe Nanocrystals: Toward Highly Fluorescent CdTe/CdS Core−Shell Structure , 2004 .

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

[97]  Michael C. Wilson,et al.  Surfactant-assisted synthesis of water-soluble and biocompatible semiconductor quantum dot micelles. , 2005, Nano letters.

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

[99]  K Dane Wittrup,et al.  Monovalent, reduced-size quantum dots for imaging receptors on living cells , 2008, Nature Methods.

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

[101]  Igor L. Medintz,et al.  Synthesis of compact multidentate ligands to prepare stable hydrophilic quantum dot fluorophores. , 2005, Journal of the American Chemical Society.

[102]  F. Pinaud,et al.  Comparison of photophysical and colloidal properties of biocompatible semiconductor nanocrystals using fluorescence correlation spectroscopy. , 2005, Analytical chemistry.