Micelle-Encapsulated Quantum Dot-Porphyrin Assemblies as in Vivo Two-Photon Oxygen Sensors.

Micelles have been employed to encapsulate the supramolecular assembly of quantum dots with palladium(II) porphyrins for the quantification of O2 levels in aqueous media and in vivo. Förster resonance energy transfer from the quantum dot (QD) to the palladium porphyrin provides a means for signal transduction under both one- and two-photon excitation. The palladium porphyrins are sensitive to O2 concentrations in the range of 0-160 Torr. The micelle-encapsulated QD-porphyrin assemblies have been employed for in vivo multiphoton imaging and lifetime-based oxygen measurements in mice with chronic dorsal skinfold chambers or cranial windows. Our results establish the utility of the QD-micelle approach for in vivo biological sensing applications.

[1]  Sung-Woo Park,et al.  Encapsulation of CdSe/ZnS quantum dots in poly(ethylene glycol)-poly(D,L-lactide) micelle for biomedical imaging and detection , 2007 .

[2]  R. Jain,et al.  Metabolic tumor profiling with pH, oxygen, and glucose chemosensors on a quantum dot scaffold. , 2013, Inorganic chemistry.

[3]  R. Jain.  Normalizing tumor microenvironment to treat cancer: bench to bedside to biomarkers. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  P. Okunieff,et al.  Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. , 1989, Cancer research.

[5]  Suhua Wang,et al.  Nitric oxide switches on the photoluminescence of molecularly engineered quantum dots. , 2009, Journal of the American Chemical Society.

[6]  R. Battino,et al.  The Solubility of Oxygen and Ozone in Liquids , 1983 .

[7]  W.Phillip Helman,et al.  Quantum Yields for the Photosensitized Formation of the Lowest Electronically Excited Singlet State of Molecular Oxygen in Solution , 1993 .

[8]  Euan R. Kay,et al.  Conformational control of energy transfer: a mechanism for biocompatible nanocrystal-based sensors. , 2013, Angewandte Chemie.

[9]  Rakesh K. Jain,et al.  Normalizing tumor vasculature with anti-angiogenic therapy: A new paradigm for combination therapy , 2001, Nature Medicine.

[10]  A. Losev,et al.  Absorbance and emission properties of palladium octaethylporphyrin and palladium tetrahexylporphyrin in solution and in phospholipid membranes , 1990 .

[11]  W. Webb,et al.  Nonlinear magic: multiphoton microscopy in the biosciences , 2003, Nature Biotechnology.

[12]  Shimon Weiss,et al.  Singlet oxygen production by Peptide-coated quantum dot-photosensitizer conjugates. , 2007, Journal of the American Chemical Society.

[13]  S. J. Chen,et al.  Direct determination of the refractive index and thickness of a biolayer based on coupled waveguide-surface plasmon resonance mode. , 2006, Optics letters.

[14]  Young S. Choi,et al.  One‐ and two‐photon fluorescence excitation spectra of the 2 1Ag states of linear tetraenes in free jet expansions , 1995 .

[15]  Chih-Wei Lai,et al.  The empirical correlation between size and two-photon absorption cross section of CdSe and CdTe quantum dots. , 2006, Small.

[16]  Horst Weller,et al.  Controlling the physical and biological properties of highly fluorescent aqueous quantum dots using block copolymers of different size and shape. , 2013, ACS nano.

[17]  R. Jain,et al.  Antiangiogenesis strategies revisited: from starving tumors to alleviating hypoxia. , 2014, Cancer cell.

[18]  John F. Callan,et al.  Water soluble quantum dots as hydrophilic carriers and two-photon excited energy donors in photodynamic therapy , 2012 .

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

[20]  Philippe Guyot-Sionnest,et al.  Photoluminescence of single semiconductor nanocrystallites by two-photon excitation microscopy , 1994 .

[21]  Dai Fukumura,et al.  Imaging angiogenesis and the microenvironment   , 2008, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[22]  Moungi G. Bawendi,et al.  On the Absorption Cross Section of CdSe Nanocrystal Quantum Dots , 2002 .

[23]  W. Denk,et al.  Deep tissue two-photon microscopy , 2005, Nature Methods.

[24]  E. Rofstad,et al.  Acidic extracellular pH promotes experimental metastasis of human melanoma cells in athymic nude mice. , 2006, Cancer research.

[25]  K. Bonin,et al.  Two-photon electric-dipole selection rules , 1984 .

[26]  A. N. Bashkatov,et al.  Optical properties of human skin, subcutaneous and mucous tissues in the wavelength range from 400 to 2000 nm , 2005 .

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

[28]  John E. Bercaw,et al.  NMR Chemical Shifts of Trace Impurities: Common Laboratory Solvents, Organics, and Gases in Deuterated Solvents Relevant to the Organometallic Chemist , 2010 .

[29]  P. Barthélémy,et al.  Quantum dot lipid oligonucleotide bioconjugates: toward a new anti-microRNA nanoplatform. , 2013, Bioconjugate chemistry.

[30]  R. Jain,et al.  Compact biocompatible quantum dots via RAFT-mediated synthesis of imidazole-based random copolymer ligand. , 2009, Journal of the American Chemical Society.

[31]  M. Intaglietta,et al.  pO2Measurements in Arteriolar Networks , 1996 .

[32]  I. Z. Steinberg.  Long-range nonradiative transfer of electronic excitation energy in proteins and polypeptides. , 1971, Annual review of biochemistry.

[33]  R. Jain,et al.  Angiogenesis, microvascular architecture, microhemodynamics, and interstitial fluid pressure during early growth of human adenocarcinoma LS174T in SCID mice. , 1992, Cancer research.

[34]  A. Adler,et al.  Mechanistic Investigations of Porphyrin Syntheses. I. Preliminary Studies on ms-Tetraphenylporphin , 1964 .

[35]  Geoffrey F. Strouse,et al.  Nanosecond exciton recombination dynamics in colloidal CdSe quantum dots under ambient conditions , 2003 .

[36]  Feng Gao,et al.  Oxygen microscopy by two-photon-excited phosphorescence. , 2008, Chemphyschem : a European journal of chemical physics and physical chemistry.

[37]  Marcos Intaglietta,et al.  Oxygen gradients in the microcirculation. , 2003, Physiological reviews.

[38]  M. Nurunnabi,et al.  Oral delivery of near-infrared quantum dot loaded micelles for noninvasive biomedical imaging. , 2012, ACS applied materials & interfaces.

[39]  Daniel G Nocera,et al.  Photo-ribonucleotide reductase β2 by selective cysteine labeling with a radical phototrigger , 2011, Proceedings of the National Academy of Sciences.

[40]  M. Bawendi,et al.  Two-photon oxygen sensing with quantum dot-porphyrin conjugates. , 2013, Inorganic chemistry.

[41]  M. Bawendi,et al.  Two-photon absorbing nanocrystal sensors for ratiometric detection of oxygen. , 2009, Journal of the American Chemical Society.

[42]  J. Horwitz,et al.  Two‐photon excitation spectroscopy and excited state decay kinetics of isolated diphenylbutadiene , 1985 .

[43]  A. Adler,et al.  A simplified synthesis for meso-tetraphenylporphine , 1967 .

[44]  Dai Fukumura,et al.  Tumor Microvasculature and Microenvironment: Novel Insights Through Intravital Imaging in Pre‐Clinical Models , 2010, Microcirculation.

[45]  R. Winslow,et al.  Microvascular and tissue oxygen distribution. , 1996, Cardiovascular research.

[46]  R. Jain.  Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy , 2005, Science.

[47]  Jerome Mertz,et al.  Epifluorescence collection in two-photon microscopy. , 2002, Applied optics.

[48]  Kemin Wang,et al.  Single nanoparticle imaging and characterization of different phospholipid-encapsulated quantum dot micelles. , 2012, Langmuir : the ACS journal of surfaces and colloids.

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

[50]  Zhihong Liu,et al.  Construction of a molecular beacon based on two-photon excited fluorescence resonance energy transfer with quantum dot as donor. , 2011, Chemical communications.

[51]  J. Callis,et al.  Porphyrins XXII: Fast fluorescence, delayed fluorescence, and quasiline structure in palladium and platinum complexes☆ , 1971 .

[52]  S. Jacques.  Optical properties of biological tissues: a review , 2013, Physics in medicine and biology.

[53]  Yiyong Mai,et al.  Selective localization of preformed nanoparticles in morphologically controllable block copolymer aggregates in solution. , 2012, Accounts of chemical research.

[54]  J. Lakowicz.  Principles of fluorescence spectroscopy , 1983 .

[55]  Claudia Calcagno,et al.  Nanocrystal core high-density lipoproteins: a multimodality contrast agent platform. , 2008, Nano letters.

[56]  I SUMEGI,et al.  [The porphyrins]. , 1954, Orvosi hetilap.

[57]  Triantafyllos Stylianopoulos,et al.  Delivery of molecular and nanoscale medicine to tumors: transport barriers and strategies. , 2011, Annual review of chemical and biomolecular engineering.

[58]  V. Torchilin,et al.  Quantum dots encapsulated in phospholipid micelles for imaging and quantification of tumors in the near-infrared region. , 2009, Nanomedicine : nanotechnology, biology, and medicine.

[59]  Rakesh K. Jain,et al.  Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases , 2011, Nature Reviews Drug Discovery.

[60]  J Folkman,et al.  Transplacental carcinogenesis by stilbestrol. , 1971, The New England journal of medicine.

[61]  Th. Förster.  Zwischenmolekulare Energiewanderung und Fluoreszenz , 1948 .

[62]  N. Turro.  Modern Molecular Photochemistry , 1978 .

[63]  R. Jain,et al.  A Nanocrystal-based Ratiometric pH Sensor for Natural pH Ranges. , 2012, Chemical Science.

[64]  J. Folkman.  Opinion: Angiogenesis: an organizing principle for drug discovery? , 2007, Nature Reviews Drug Discovery.

[65]  Delyle Eastwood,et al.  Porphyrins: XVIII. Luminescence of (Co), (Ni), Pd, Pt complexes☆ , 1970 .

[66]  P. Carmeliet,et al.  Angiogenesis in cancer and other diseases , 2000, Nature.

[67]  W. Webb,et al.  Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[68]  Quynh-Thu Le,et al.  Lysyl oxidase is essential for hypoxia-induced metastasis , 2006, Nature.

[69]  R. Jain,et al.  Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy , 2012, Proceedings of the National Academy of Sciences.

[70]  Atsushi Kobayashi,et al.  Reevaluation of absolute luminescence quantum yields of standard solutions using a spectrometer with an integrating sphere and a back-thinned CCD detector. , 2009, Physical chemistry chemical physics : PCCP.

[71]  Bradley B. Collier,et al.  Microparticle ratiometric oxygen sensors utilizing near-infrared emitting quantum dots. , 2011, The Analyst.

[72]  D. Nocera,et al.  Excited-state dynamics of cofacial pacman porphyrins , 2002 .

[73]  Ute Resch-Genger,et al.  Determination of the Fluorescence Quantum Yield of Quantum Dots: Suitable Procedures and Achievable Uncertainties , 2009 .

[74]  C. Tomes.  CHEMISTRY AND PHYSICS , 1903 .

[75]  Rakesh K. Jain,et al.  Interstitial pH and pO2 gradients in solid tumors in vivo: High-resolution measurements reveal a lack of correlation , 1997, Nature Medicine.

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

[77]  Marc Dellian,et al.  Acid production in glycolysis-impaired tumors provides new insights into tumor metabolism. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[78]  P. Comoglio,et al.  Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. , 2003, Cancer cell.

[79]  M. Sinaasappel,et al.  Calibration of Pd-porphyrin phosphorescence for oxygen concentration measurements in vivo. , 1996, Journal of applied physiology.

[80]  T. Pons,et al.  Synthesis, encapsulation, purification and coupling of single quantum dots in phospholipid micelles for their use in cellular and in vivo imaging , 2007, Nature Protocols.

[81]  Thomas Pons,et al.  Fluorine-18-labeled phospholipid quantum dot micelles for in vivo multimodal imaging from whole body to cellular scales. , 2008, Bioconjugate chemistry.

[82]  M. Ducros,et al.  Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels , 2011, Nature Medicine.

[83]  R K Jain,et al.  Vascular permeability and microcirculation of gliomas and mammary carcinomas transplanted in rat and mouse cranial windows. , 1994, Cancer research.

[84]  Dai Fukumura,et al.  Tumor microenvironment abnormalities: Causes, consequences, and strategies to normalize , 2007, Journal of cellular biochemistry.

[85]  Hongyou Fan,et al.  Surfactant-assisted synthesis of water-soluble and biocompatible semiconductor quantum dot-micelles , 2005, SPIE BiOS.

[86]  P. Merkel,et al.  Remarkable solvent effects on the lifetime of 1.DELTA.g oxygen , 1972 .

[87]  Moungi G Bawendi,et al.  Compact biocompatible quantum dots functionalized for cellular imaging. , 2008, Journal of the American Chemical Society.

[88]  Li-wei Liu,et al.  Optimizing the synthesis of red- and near-infrared CuInS2 and AgInS2 semiconductor nanocrystals for bioimaging. , 2013, The Analyst.

[89]  Emiri T. Mandeville,et al.  Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue , 2010, Nature Methods.

[90]  D. Nocera,et al.  Deciphering radical transport in the large subunit of class I ribonucleotide reductase. , 2011, Journal of the American Chemical Society.

[91]  Dai Fukumura,et al.  Tumor microvasculature and microenvironment: targets for anti-angiogenesis and normalization. , 2007, Microvascular research.

[92]  Xiaobo Chen,et al.  Semiconductor quantum dots for photodynamic therapy. , 2003, Journal of the American Chemical Society.

[93]  W. Law,et al.  Synthesis of cRGD-peptide conjugated near-infrared CdTe/ZnSe core-shell quantum dots for in vivo cancer targeting and imaging. , 2010, Chemical communications.