Advertisement

NIR-Fluorescent Multidye Silica Nanoparticles with Large Stokes Shifts for Versatile Biosensing Applications

  • Gala ChapmanEmail author
  • Gabor Patonay
ORIGINAL ARTICLE
  • 31 Downloads

Abstract

We have synthesized and characterized of a series of single and multidye copolymerized nanoparticles with large to very large Stokes shifts (100 to 255 nm) for versatile applications as standalone or multiplexed probes in biological matrices. Nanoparticles were prepared via the Stöber method and covalently copolymerized with various combinations of three dyes, including one novel aminocyanine dye. Covalently encapsulated dyes exhibited no significant leakage from the nanoparticle matrix after more than 200 days of storage in ethanol. Across multiple batches of nanoparticles with varying dye content, the average yields and average radii were found to be highly reproducible. Furthermore, the batch to batch variability in the relative amounts of dye incorporated was small (relative standard deviations <2.3%). Quantum yields of dye copolymerized nanoparticles were increased 50% to 1000% relative to those of their respective dye-silane conjugates, and fluorescence intensities were enhanced by approximately three orders of magnitude. Prepared nanoparticles were surface modified with polyethylene glycol and biotin and bound to streptavidin microspheres as a proof of concept. Under single wavelength excitation, microsphere-bound nanoparticles displayed readily distinguishable fluorescence signals at three different emission wavelengths, indicating their potential applications to multicolor sensing. Furthermore, nanoparticles modified with polyethylene glycol and biotin demonstrated hematoprotective qualities and reduced nonspecific binding of serum proteins, indicating their potential suitability to in vivo imaging applications.

Keywords

Fluorescent silica nanoparticles Resonance energy transfer Large stokes shift Near-infrared fluorescence Multicolor assay Biocompatible nanoparticles 

Notes

Acknowledgements

We would like to thank Dr. Robert Simmons for supplying TEM spectra, Sharon Flores and Gyliann Peña for providing hematology samples, Maksim Kvetny and Dr. Gangli Wang for assisting with fluorescence microscopy instrumentation and image collection, Dr. Rudolph Johnson for providing spectrofluorometer access, and Stephanie Negrete and Dr. Jonas Perez for facilitating the usage of this instrument. This research was supported in part with a Georgia State University Dissertation Grant.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

10895_2018_2339_MOESM1_ESM.pdf (548 kb)
ESM 1 (PDF 548 kb)

References

  1. 1.
    Fluorescence Microscopy and Fluorescent Probes (1998), vol 2. Plenum Press, New York & LondonGoogle Scholar
  2. 2.
    Lakowicz JR (2006) Principles of fluorescence spectroscopy, 3rd edn. Springer Science+Business Media, LLC, New YorkGoogle Scholar
  3. 3.
    Doré K, Leclerc M, Boudreau D (2006) Investigation of a fluorescence signal amplification mechanism used for the direct molecular detection of nucleic acids. J Fluoresc 16:259–265.  https://doi.org/10.1007/s10895-006-0098-4 Google Scholar
  4. 4.
    Estévez MC, O’Donoghue MB, Chen X, Tan W (2009) Highly fluorescent dye-doped silica nanoparticles increase flow cytometry sensitivity for cancer cell monitoring. Nano Res 2(6):448–461.  https://doi.org/10.1007/s12274-009-9041-8 Google Scholar
  5. 5.
    Weissleder R, Tung C-H, Mahmood U, Bogdanov A Jr (1999) In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nat Biotechnol 17:375–378.  https://doi.org/10.1038/7933 Google Scholar
  6. 6.
    Shalon D, Smith SJ, Brown PO (1996) A DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization. Genome Res 6(7):639–645.  https://doi.org/10.1101/gr.6.7.639 Google Scholar
  7. 7.
    Lanz E, Gregor M, Slavík J, Kotyk A (1997) Use of FITC as a fluorescent probe for intracellular pH measurement. J Fluoresc 7(4):317–319.  https://doi.org/10.1023/A:1022586127784 Google Scholar
  8. 8.
    Dawson PL, Acton JC (2018) 22 - impact of proteins on food color. In: Yada RY (ed) Proteins in food processing, Second edn. Woodhead Publishing, Cambridge, pp 599–638.  https://doi.org/10.1016/B978-0-08-100722-8.00023-1
  9. 9.
    Zipfel WR, Williams RM, Christie R, Nikitin AY, Hyman BT, Webb WW (2003) Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation. Proc Natl Acad Sci U S A 100(12):7075–7080.  https://doi.org/10.1073/pnas.0832308100 Google Scholar
  10. 10.
    Pastrana E (2012) Near-infrared probes. Nat Methods 10:36.  https://doi.org/10.1038/nmeth.2294 Google Scholar
  11. 11.
    Swamy A, Mason J, Lee H, Meadows F, Baars M, Strekowski L, Patonay G (2006) Near-infrared Absorption/Luminescence Measurements. In: Meyers RA, Warner IM (eds) Encyclopedia of Analytical Chemistry.  https://doi.org/10.1002/9780470027318.a5410
  12. 12.
    Williams ATR, Winfield SA, Miller JN (1983) Relative fluorescence quantum yields using a computer-controlled luminescence spectrometer. Analyst 108(1290):1067–1071.  https://doi.org/10.1039/AN9830801067 Google Scholar
  13. 13.
    Jares-Erijman EA, Jovin TM (2003) FRET imaging. Nat Biotechnol 21:1387–1395.  https://doi.org/10.1038/nbt896 Google Scholar
  14. 14.
    Wu X, Sun X, Guo Z, Tang J, Shen Y, James TD, Tian H, Zhu W (2014) In vivo and in situ tracking Cancer chemotherapy by highly Photostable NIR fluorescent Theranostic prodrug. J Am Chem Soc 136(9):3579–3588.  https://doi.org/10.1021/ja412380j Google Scholar
  15. 15.
    Lee H, Mason JC, Achilefu S (2008) Synthesis and spectral properties of near-infrared Aminophenyl-, Hydroxyphenyl-, and phenyl-substituted Heptamethine Cyanines. J Org Chem 73(2):723–725.  https://doi.org/10.1021/jo701793h Google Scholar
  16. 16.
    Levitz A, Marmarchi F, Henary M (2018) Synthesis and optical properties of near-infrared meso-phenyl-substituted symmetric Heptamethine cyanine dyes. Molecules 23(2).  https://doi.org/10.3390/molecules23020226
  17. 17.
    Matichak JD, Hales JM, Barlow S, Perry JW, Marder SR (2011) Dioxaborine- and indole-terminated Polymethines: effects of bridge substitution on absorption spectra and third-order polarizabilities. J Phys Chem A 115(11):2160–2168.  https://doi.org/10.1021/jp110425r Google Scholar
  18. 18.
    Dewar MJS (1950) 478. Colour and constitution. Part I. Basic dyes. J Chem Soc (0):2329–2334.  https://doi.org/10.1039/JR9500002329
  19. 19.
    Knott EB (1951) 227. The colour of organic compounds. Part I. A general colour rule. J Chem Soc (0):1024–1028.  https://doi.org/10.1039/JR9510001024
  20. 20.
    Peng X, Song F, Lu E, Wang Y, Zhou W, Fan J, Gao Y (2005) Heptamethine cyanine dyes with a large stokes shift and strong fluorescence: a paradigm for excited-state intramolecular charge transfer. J Am Chem Soc 127(12):4170–4171.  https://doi.org/10.1021/ja043413z Google Scholar
  21. 21.
    Gorris HH, Saleh SM, Groegel DBM, Ernst S, Reiner K, Mustroph H, Wolfbeis OS (2011) Long-wavelength absorbing and fluorescent chameleon labels for proteins, peptides, and amines. Bioconjug Chem 22(7):1433–1437.  https://doi.org/10.1021/bc200192k Google Scholar
  22. 22.
    Menéndez GO, Eva Pichel M, Spagnuolo CC, Jares-Erijman EA (2013) NIR fluorescent biotinylated cyanine dye: optical properties and combination with quantum dots as a potential sensing device. Photochemical & Photobiological Sciences 12(2):236–240.  https://doi.org/10.1039/C2PP25174D Google Scholar
  23. 23.
    Liu A, Wu L, He Z, Zhou J (2011) Development of highly fluorescent silica nanoparticles chemically doped with organic dye for sensitive DNA microarray detection. Anal Bioanal Chem 401(6):2003–2011.  https://doi.org/10.1007/s00216-011-5258-y Google Scholar
  24. 24.
    Zhang W-H, Hu X-X, Zhang X-B (2016) Dye-doped fluorescent silica nanoparticles for live cell and in vivo bioimaging. Nanomaterials 6(81):1–17.  https://doi.org/10.3390/nano6050081 Google Scholar
  25. 25.
    Nooney RI, McCormack E, McDonagh C (2012) Optimization of size, morphology and colloidal stability of fluorescein dye-doped silica NPs for application in immunoassays. Anal Bioanal Chem 404(10):2807–2818.  https://doi.org/10.1007/s00216-012-6224-z Google Scholar
  26. 26.
    Larson DR, Ow H, Vishwasrao HD, Heikal AA, Wiesner U, Webb WW (2008) Silica nanoparticle architecture determines radiative properties of encapsulated fluorophores. Chem Mater 20(8):2677–2684.  https://doi.org/10.1021/cm7026866 Google Scholar
  27. 27.
    Wang L, Yang C, Tan W (2005) Dual-Luminophore-doped silica nanoparticles for multiplexed signaling. Nano Lett 5(1):37–43.  https://doi.org/10.1021/nl048417g Google Scholar
  28. 28.
    Wang L, Zhao W, O’Donoghu MB, Tan W (2007) Fluorescent nanoparticles for multiplexed Bacteria monitoring. Bioconjug Chem 18(2):297–301.  https://doi.org/10.1021/bc060255n Google Scholar
  29. 29.
    Nakamura M, Shono M, Ishimura K (2007) Synthesis, characterization, and biological applications of multifluorescent silica nanoparticles. Anal Chem 79(17):6507–6514.  https://doi.org/10.1021/ac070394d Google Scholar
  30. 30.
    Biffi S, Petrizza L, Rampazzo E, Voltan R, Sgarzi M, Garrovo C, Prodi L, Andolfi L, Agnoletto C, Zauli G, Secchiero P (2014) Multiple dye-doped NIR-emitting silica nanoparticles for both flow cytometry and in vivo imaging. RSC Adv 4(35):18278–18285.  https://doi.org/10.1039/C4RA01535E Google Scholar
  31. 31.
    Kumar R, Roy I, Ohulchanskyy TY, Goswami LN, Bonoiu AC, Bergey EJ, Tramposch KM, Maitra A, Prasad PN (2008) Covalently dye-linked, surface-controlled, and bioconjugated organically modified silica nanoparticles as targeted probes for optical imaging. ACS Nano 2(3):449–456.  https://doi.org/10.1021/nn700370b Google Scholar
  32. 32.
    Wang Z, Hong X, Zong S, Tang C, Cui Y, Zheng Q (2015) BODIPY-doped silica nanoparticles with reduced dye leakage and enhanced singlet oxygen generation. Sci Rep 5(12602).  https://doi.org/10.1038/srep12602
  33. 33.
    Labéguerie-Egéa J, McEvoy HM, McDonagh C (2011) Synthesis, characterisation and functionalisation of luminescent silica nanoparticles. J Nanopart Res 13(12):6455–6465.  https://doi.org/10.1007/s11051-011-0539-0 Google Scholar
  34. 34.
    Edelstein A, Amodaj N, Hoover K, Vale R, Stuurman N (2010) Computer control of microscopes using μManager. Curr Protoc Mol Biol 92(1):14.20.11–14.20.17.  https://doi.org/10.1002/0471142727.mb1420s92 Google Scholar
  35. 35.
    Edelstein AD, Tsuchida MA, Amodaj N, Pinkard H, Vale RD, Stuurman N (2014) Advanced methods of microscope control using μManager software. J Biol Methods 1(2):e10.  https://doi.org/10.14440/jbm.2014.36 Google Scholar
  36. 36.
    Meijering EHW, Niessen WJ, Viergever MA (2001) Quantitative evaluation of convolution-based methods for medical image interpolation. Med Image Anal 5(2):111–126.  https://doi.org/10.1016/S1361-8415(00)00040-2 Google Scholar
  37. 37.
    Landini G Advanced shape analysis with ImageJ. In: Proceedings of the second ImageJ user and developer conference, Luxembourg, 6–7 November 2008. pp 116–121Google Scholar
  38. 38.
    Stöber W, Fink A, Bohn E (1968) Controlled growth of monodisperse silica spheres in the micron size range. J Colloid Interface Sci 26(1):62–69.  https://doi.org/10.1016/0021-9797(68)90272-5 Google Scholar
  39. 39.
    Nooney RI, McCahey CMN, Stranik O, Le Guevel X, McDonagh C, MacCraith BD (2009) Experimental and theoretical studies of the optimisation of fluorescence from near-infrared dye-doped silica nanoparticles. Anal Bioanal Chem 393(4):1143–1149.  https://doi.org/10.1007/s00216-008-2418-9 Google Scholar
  40. 40.
    Jung H-S, Moon D-S, Lee J-K (2012) Quantitative analysis and efficient surface modification of silica nanoparticles. J Nanomater 2012:8.  https://doi.org/10.1155/2012/593471 Google Scholar
  41. 41.
    Seminar on Adsorption BEL Japan, Inc. http://www.microtrac-bel.com/en/tech/bel/seminar06.html. Accessed 26 March 2018
  42. 42.
    Zielinski JM, Kettle L (2013) Physical Characterization: Surface Area and Porosity. Intertek Chemicals and Pharmaceuticals. www.intertek.com/chemical-physical-characterization-surface-area-and-porosity/. Accessed 19 August 2018
  43. 43.
    Murali VS, Wang R, Mikoryak CA, Pantano P, Draper R (2015) Rapid detection of polyethylene glycol sonolysis upon functionalization of carbon nanomaterials. Exp Biol Med (Maywood) 240(9):1147–1151.  https://doi.org/10.1177/1535370214567615 Google Scholar
  44. 44.
    Benson RA, Kues HA (1978) Fluorescence properties of indocyanine green as related to angiography. Phys Med Biol 23(1):159–163Google Scholar
  45. 45.
    Ornelas CL, Durandin A, Canary JW, Pennell R, Liebes LF, Weck M (2011) Combining Aminocyanine dyes with polyamide Dendrons: a promising strategy for imaging in the near-infrared region. Chem Eur J 17:3619–3629Google Scholar
  46. 46.
    Mchedlov-Petrossyan NO, Kukhtik VI, Bezugliy VD (2003) Dissociation, tautomerism and electroreduction of xanthene and sulfonephthalein dyes in N,N-dimethylformamide and other solvents. J Phys Org Chem 16(7):380–397.  https://doi.org/10.1002/poc.654 Google Scholar
  47. 47.
    Valeur B (2001) Molecular fluorescence: principles and applications. Wiley-VCH, WeinheimGoogle Scholar
  48. 48.
    Nyffenegger R, Quellet C, Ricka J (1993) Synthesis of fluorescent, monodisperse, colloidal silica particles. J Colloid Interface Sci 159(1):150–157.  https://doi.org/10.1006/jcis.1993.1306 Google Scholar
  49. 49.
    Palantavida S, Tang R, Sudlow GP, Akers WJ, Achilefu S, Sokolov I (2014) Ultrabright NIR fluorescent mesoporous silica nanoparticles. J Mater Chem B 2(20):3107–3114.  https://doi.org/10.1039/C4TB00287C Google Scholar
  50. 50.
    Bhattacharyya S, Prashanthi S, Bangal PR, Patra A (2013) Photophysics and dynamics of dye-doped conjugated polymer nanoparticles by time-resolved and fluorescence correlation spectroscopy. J Phys Chem C 117(50):26750–26759.  https://doi.org/10.1021/jp409570f Google Scholar
  51. 51.
    Chen X, Zhang X, Xia L-Y, Wang H-Y, Chen Z, Wu F-G (2018) One-step synthesis of Ultrasmall and Ultrabright Organosilica Nanodots with 100% photoluminescence quantum yield: long-term lysosome imaging in living, fixed, and Permeabilized cells. Nano Lett 18(2):1159–1167.  https://doi.org/10.1021/acs.nanolett.7b04700 Google Scholar
  52. 52.
    Soper SA, Nutter HL, Keller RA, Davis LM, Shera EB (1993) The photophysical constants of several fluorescent dyes pertaining to ultrasensitive fluorescence spectroscopy. Photochem Photobiol 57(s1):972–977.  https://doi.org/10.1111/j.1751-1097.1993.tb02957.x Google Scholar
  53. 53.
    Unruh JR, Gokulrangan G, Wilson GS, Johnson CK (2005) Fluorescence properties of fluorescein, Tetramethylrhodamine and Texas red linked to a DNA aptamer. Photochem Photobiol 81(3):682–690.  https://doi.org/10.1111/j.1751-1097.2005.tb00244.x Google Scholar
  54. 54.
    Martin MM, Lindqvist L (1975) The pH dependence of fluorescein fluorescence. J Lumin 10(6):381–390.  https://doi.org/10.1016/0022-2313(75)90003-4 Google Scholar
  55. 55.
    Klonis N, Sawyer WH (2003) The Thiourea group modulates the fluorescence emission decay of fluorescein-labeled molecules. Photochem Photobiol 77(5):502–509.  https://doi.org/10.1562/0031-8655(2003)0770502TTGMTF2.0.CO2 Google Scholar
  56. 56.
    Miura T, Urano Y, Tanaka K, Nagano T, Ohkubo K, Fukuzumi S (2003) Rational design principle for modulating fluorescence properties of fluorescein-based probes by Photoinduced Electron transfer. J Am Chem Soc 125(28):8666–8671.  https://doi.org/10.1021/ja035282s Google Scholar
  57. 57.
    Hu Z, Tan J, Lai Z, Zheng R, Zhong J, Wang Y, Li X, Yang N, Li J, Yang W, Huang Y, Zhao Y, Lu X (2017) Aptamer combined with fluorescent silica nanoparticles for detection of hepatoma cells. Nanoscale Res Lett 12(96):96.  https://doi.org/10.1186/s11671-017-1890-6 Google Scholar
  58. 58.
    Jokerst JV, Lobovkina T, Zare RN, Gambhir SS (2011) Nanoparticle PEGylation for imaging and therapy. Nanomedicine 6(4):715–728.  https://doi.org/10.2217/nnm.11.19 Google Scholar
  59. 59.
    Wilchek M, Bayer EA (eds) (1990) Avidin-biotin technology. Methods in Enzymology, vol, vol 184. Academic Press, San DiegoGoogle Scholar
  60. 60.
    Lesniak A, Fenaroli F, Monopoli MP, Åberg C, Dawson KA, Salvati A (2012) Effects of the presence or absence of a protein Corona on silica nanoparticle uptake and impact on cells. ACS Nano 6(7):5845–5857.  https://doi.org/10.1021/nn300223w Google Scholar
  61. 61.
    Zhou G, Li L, Xing J, Cai J, Chen J, Liu P, Gu N, Ji M (2017) Layer-by-layer construction of lipid bilayer on mesoporous silica nanoparticle to improve its water suspensibility and hemocompatibility. J Sol-Gel Sci Technol 82(2):490–499.  https://doi.org/10.1007/s10971-017-4330-2 Google Scholar
  62. 62.
    Abdelwahab WM, Phillips E, Patonay G (2018) Preparation of fluorescently labeled silica nanoparticles using an amino acid-catalyzed seeds regrowth technique: application to latent fingerprints detection and hemocompatibility studies. J Colloid Interface Sci 512:801–811.  https://doi.org/10.1016/j.jcis.2017.10.062 Google Scholar
  63. 63.
    Slowing II, Wu C-W, Vivero-Escoto JL, Lin VS-Y (2009) Mesoporous silica nanoparticles for reducing hemolytic activity towards mammalian red blood cells. Small 5(1):57–62.  https://doi.org/10.1002/smll.200800926 Google Scholar
  64. 64.
    Lundqvist M, Sethson I, Jonsson B-H (2004) Protein adsorption onto silica nanoparticles: conformational changes depend on the Particles' curvature and the protein stability. Langmuir 20(24):10639–10647.  https://doi.org/10.1021/la0484725 Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of ChemistryGeorgia State UniversityAtlantaUSA

Personalised recommendations