Design and Engineering of Multifunctional Quantum Dot-Based Nanoparticles for Simultaneous Therapeutic-Diagnostic Applications

Quantum dots (QD) are semiconducting nanocrystals that have recently received a lot of interest because of their efficacy as fluorescent probes. They offer a significant increase in photostability and fluorescence lifetime compared to more traditional organic dye-based probes; however, some concern from their potential in vivo use due to their chemical composition and their nanoscale dimensions exists. Within this chapter, we discuss current knowledge about the fluorescence properties and pharmacological profile of quantum dots, showing how these characteristics can be altered after incorporation within previously established drug delivery systems for the formation of novel hybrid systems. The incorporation of therapeutic agents into such hybrid systems can further result in the construction of theranostic devices, namely, QD-based theranostics. Alternatively, conjugation of quantum dots to therapeutic moieties can be used as a scaffold for theranostic device design. This chapter will discuss the current progress in QD-based theranostics.

[1]  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.

[2]  Andreas Kornowski,et al.  Highly Luminescent Monodisperse CdSe and CdSe/ZnS Nanocrystals Synthesized in a Hexadecylamine-Trioctylphosphine Oxide-Trioctylphospine Mixture. , 2001, Nano letters.

[3]  Shuming Nie,et al.  Bioconjugated quantum dots for in vivo molecular and cellular imaging. , 2008, Advanced drug delivery reviews.

[4]  Alexander M Seifalian,et al.  Quantum dots and their potential biomedical applications in photosensitization for photodynamic therapy. , 2009, Nanomedicine.

[5]  Kostas Kostarelos,et al.  Lipid-quantum dot bilayer vesicles enhance tumor cell uptake and retention in vitro and in vivo. , 2008, ACS nano.

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

[7]  R. E. Schaak,et al.  ZnO-templated synthesis of wurtzite-type ZnS and ZnSe nanoparticles. , 2009, Journal of the American Chemical Society.

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

[9]  D. Tomalia,et al.  Dendronization of gold and CdSe/cdS (core–shell) quantum dots with tomalia type, thiol core, functionalized poly(amidoamine) (PAMAM) dendrons , 2005 .

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

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

[12]  Kostas Kostarelos,et al.  Functionalized-quantum-dot-liposome hybrids as multimodal nanoparticles for cancer. , 2008, Small.

[13]  Sung Ju Cho,et al.  Quantum dot-induced cell death involves Fas upregulation and lipid peroxidation in human neuroblastoma cells , 2007, Journal of nanobiotechnology.

[14]  Kevin C Weng,et al.  Targeted tumor cell internalization and imaging of multifunctional quantum dot-conjugated immunoliposomes in vitro and in vivo. , 2008, Nano letters.

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

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

[17]  Tian-Cai Liu,et al.  Study on molecular interactions between proteins on live cell membranes using quantum dot-based fluorescence resonance energy transfer , 2008, Analytical and bioanalytical chemistry.

[18]  Kostas Kostarelos,et al.  Tumor targeting of functionalized quantum dot-liposome hybrids by intravenous administration. , 2009, Molecular pharmaceutics.

[19]  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.

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

[21]  M. Bawendi,et al.  (CdSe)ZnS Core-Shell Quantum Dots - Synthesis and Characterization of a Size Series of Highly Luminescent Nanocrystallites , 1997 .

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

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

[24]  Frank W. Wise,et al.  Optical Properties of Colloidal PbSe Nanocrystals , 2002 .

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

[26]  Rajan P. Kulkarni,et al.  Quantum dots are powerful multipurpose vital labeling agents in zebrafish embryos , 2005, Developmental dynamics : an official publication of the American Association of Anatomists.

[27]  Michael J Sailor,et al.  Micellar hybrid nanoparticles for simultaneous magnetofluorescent imaging and drug delivery. , 2008, Angewandte Chemie.

[28]  Weiwei Guo,et al.  Glutathione-mediated release of functional plasmid DNA from positively charged quantum dots. , 2008, Biomaterials.

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

[30]  Hong Qing,et al.  Quantum dot-labeled aptamer nanoprobes specifically targeting glioma cells , 2008, Nanotechnology.

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

[32]  Julie W. Fitzpatrick,et al.  Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy , 2005, Particle and Fibre Toxicology.

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

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

[35]  M. Moffitt,et al.  Semiconductor Quantum Dots with Environmentally Responsive Mixed Polystyrene/Poly(methyl methacrylate) Brush Layers , 2007 .

[36]  Karolin F Meyer,et al.  Quantum dot-carrier peptide conjugates suitable for imaging and delivery applications. , 2008, Bioconjugate chemistry.

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

[38]  Xiaogang Peng,et al.  Formation of high-quality CdTe, CdSe, and CdS nanocrystals using CdO as precursor. , 2001, Journal of the American Chemical Society.

[39]  Nikolai Gaponik,et al.  Comparative examination of the stability of semiconductor quantum dots in various biochemical buffers. , 2006, The journal of physical chemistry. B.

[40]  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.

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

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

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

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

[45]  Sanjiv S Gambhir,et al.  microPET-Based Biodistribution of Quantum Dots in Living Mice , 2007, Journal of Nuclear Medicine.

[46]  A. Schildan,et al.  18F- and 11C-labelling of quantum dots with n.c.a. [18F]fluoroethyltosylate and [11C]methyliodide: a feasibility study , 2010 .

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

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

[49]  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.

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

[51]  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.

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

[53]  David Sinton,et al.  Formation and shear-induced processing of quantum dot colloidal assemblies in a multiphase microfluidic chip. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[54]  M. Beard,et al.  PbTe colloidal nanocrystals: synthesis, characterization, and multiple exciton generation. , 2006, Journal of the American Chemical Society.

[55]  M. E. Kenney,et al.  Observation of non-Förster-type energy-transfer behavior in quantum dot-phthalocyanine conjugates. , 2006, Journal of the American Chemical Society.

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

[57]  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.

[58]  Christophe Danelon,et al.  Multifunctional lipid/quantum dot hybrid nanocontainers for controlled targeting of live cells. , 2006, Angewandte Chemie.

[59]  L. Cohn,et al.  Sentinel Lymph Node Mapping of the Gastrointestinal Tract by Using Invisible Light , 2006, Annals of Surgical Oncology.

[60]  Hong Ding,et al.  Functionalized near-infrared quantum dots for in vivo tumor vasculature imaging , 2010, Nanotechnology.

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

[62]  V. Torchilin.  Recent advances with liposomes as pharmaceutical carriers , 2005, Nature Reviews Drug Discovery.

[63]  Kitae E. Park,et al.  Target specific intracellular delivery of siRNA/PEI-HA complex by receptor mediated endocytosis. , 2009, Molecular pharmaceutics.

[64]  Fu-Rong Chen,et al.  Multifunctional core-shell polymeric nanoparticles for transdermal DNA delivery and epidermal Langerhans cells tracking. , 2010, Biomaterials.

[65]  R. Ewing,et al.  Conjugation of quantum dots and Fe3O4 on carbon nanotubes for medical diagnosis and treatment , 2009 .

[66]  G. Lv,et al.  Imaging and inhibition of multi-drug resistance in cancer cells via specific association with negatively charged CdTe quantum dots. , 2010, Biomaterials.

[67]  Diana Suffern,et al.  Photophysics of dopamine-modified quantum dots and effects on biological systems , 2006, Nature materials.

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

[69]  Kan Wang,et al.  Anti-HIF-1alpha antibody-conjugated pluronic triblock copolymers encapsulated with Paclitaxel for tumor targeting therapy. , 2010, Biomaterials.

[70]  Xiaogang Peng,et al.  Formation of high-quality CdS and other II-VI semiconductor nanocrystals in noncoordinating solvents: tunable reactivity of monomers. , 2002, Angewandte Chemie.

[71]  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.

[72]  Uri Banin,et al.  Synthesis of Size-Selected, Surface-Passivated InP Nanocrystals , 1996 .

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

[74]  D. Sinton,et al.  Controlled self-assembly of quantum dot-block copolymer colloids in multiphase microfluidic reactors. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[75]  Yi-Ping Ho,et al.  Quantum dot-based theranostics. , 2010, Nanoscale.

[76]  Andrey L Rogach,et al.  Drug nanocarriers labeled with near-infrared-emitting quantum dots (quantoplexes): imaging fast dynamics of distribution in living animals. , 2009, Molecular therapy : the journal of the American Society of Gene Therapy.

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

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

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

[80]  David H. Thompson,et al.  Cytosolic drug delivery using pH- and light-sensitive liposomes. , 1999, Advanced drug delivery reviews.

[81]  P. Guyot-Sionnest,et al.  Bright UV-Blue Luminescent Colloidal ZnSe Nanocrystals , 1998 .

[82]  Matthias Selke,et al.  Singlet oxygen generation from water-soluble quantum dot-organic dye nanocomposites. , 2006, Journal of the American Chemical Society.

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

[84]  K. Leong,et al.  Quantitative comparison of intracellular unpacking kinetics of polyplexes by a model constructed from quantum dot-FRET. , 2008, Molecular therapy : the journal of the American Society of Gene Therapy.

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

[86]  Jim E Riviere,et al.  Surface coatings determine cytotoxicity and irritation potential of quantum dot nanoparticles in epidermal keratinocytes. , 2007, The Journal of investigative dermatology.

[87]  Hong Ding,et al.  Biocompatible magnetofluorescent probes: luminescent silicon quantum dots coupled with superparamagnetic iron(III) oxide. , 2010, ACS nano.

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

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

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

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

[92]  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.

[93]  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 .

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

[95]  Xiaogang Peng,et al.  Kinetics of II-VI and III-V Colloidal Semiconductor Nanocrystal Growth: “Focusing” of Size Distributions , 1998 .

[96]  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.

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

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

[99]  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.

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

[101]  Kostas Kostarelos,et al.  Liposome-nanoparticle hybrids for multimodal diagnostic and therapeutic applications. , 2007, Nanomedicine.

[102]  Kostas Kostarelos,et al.  Blood circulation and tissue biodistribution of lipid--quantum dot (L-QD) hybrid vesicles intravenously administered in mice. , 2009, Bioconjugate chemistry.

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

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

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

[106]  Xiaogang Peng,et al.  Alternative Routes toward High Quality CdSe Nanocrystals , 2001 .

[107]  Xiaogang Peng,et al.  Experimental Determination of the Extinction Coefficient of CdTe, CdSe, and CdS Nanocrystals , 2003 .

[108]  P. Upadhyay.  Enhanced transdermal-immunization with diptheria-toxoid using local hyperthermia. , 2006, Vaccine.

[109]  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.

[110]  W. Wang,et al.  In vivo Imaging and Drug Storage by Quantum‐Dot‐Conjugated Carbon Nanotubes , 2008 .

[111]  T. Jovin,et al.  Targeted cellular delivery of quantum dots loaded on and in biotinylated liposomes. , 2010, Bioconjugate chemistry.

[112]  K. Leong,et al.  Evaluating the intracellular stability and unpacking of DNA nanocomplexes by quantum dots-FRET. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[113]  Hong Ding,et al.  Optically and Magnetically Doped Organically Modified Silica Nanoparticles as Efficient Magnetically Guided Biomarkers for Two-Photon Imaging of Live Cancer Cells† , 2008 .

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

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

[116]  G. Sukhorukov,et al.  Cytotoxicity of nanoparticle-loaded polymer capsules. , 2005, Talanta.

[117]  J. Benoit,et al.  Non-viral nanosystems for systemic siRNA delivery. , 2010, Pharmacological research.

[118]  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.

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

[120]  Feng Zhang,et al.  Excitation dynamics in polymer-coated semiconductor quantum dots with integrated dye molecules: The role of reabsorption , 2009 .

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

[122]  C. Maldonado,et al.  Effective photoreduction of a Pt(IV) complex with quantum dots: a feasible new light-induced method of releasing anticancer Pt(II) drugs. , 2009, Chemical communications.

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

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

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

[126]  H. Tseng,et al.  Selective inhibition of human brain tumor cells through multifunctional quantum-dot-based siRNA delivery. , 2010, Angewandte Chemie.

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

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

[129]  A. Eychmüller,et al.  Investigations on the stability of thiol stabilized semiconductor nanoparticles , 2002 .

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

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

[132]  Yan Zhang,et al.  Protease-modulated cellular uptake of quantum dots. , 2006, Nano letters.

[133]  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.

[134]  T. Giorgio,et al.  Quantitative measurement of multifunctional quantum dot binding to cellular targets using flow cytometry , 2009, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[135]  A. Anas,et al.  Clathrin-mediated endocytosis of quantum dot-peptide conjugates in living cells. , 2009, ACS nano.

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

[137]  Amane Shiohara,et al.  On the Cyto‐Toxicity Caused by Quantum Dots , 2004, Microbiology and immunology.

[138]  Andrew D. Miller,et al.  Synthetic, self-assembly ABCD nanoparticles; a structural paradigm for viable synthetic non-viral vectors. , 2005, Chemical Society Reviews.

[139]  Hak Soo Choi,et al.  Tissue- and organ-selective biodistribution of NIR fluorescent quantum dots. , 2009, Nano letters.