Skip to main content
SpringerLink
Log in

Core–shell polymeric nanoparticles comprising BODIPY and fluorescein as ultra-bright ratiometric fluorescent pH sensors

  • Paper
  • Published:
Photochemical & Photobiological Sciences Aims and scope Submit manuscript

Abstract

A new ratiometric fluorescent pH nanosensor is presented. It is based on ultrabright nanoparticles containing two spatially separated fluorophores: BODIPY covalently linked to the polystyrene core and fluorescein grafted to the nanoparticle shell. The nanoparticles comprise a large number (≥2500) of both fluorescent moieties. Their spectroscopic characteristics were studied at different pH and ionic strength. They could successfully be used to determine the solution pH between 5.5 and 7.5 by measuring the fluorescence intensity ratio of the sensor molecule (fluorescein) relative to the reference dye (BODIPY).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Notes and references

  1. C. McDonagh, C. S. Burke and B. D. MacCraith, Optical Chemical Sensors, Chem. Rev., 2008, 108, 400–422.

    Article  CAS  PubMed  Google Scholar 

  2. H. Qazi, A. Mohammad and M. Akram, Recent Progress in Optical Chemical Sensors, Sensors, 2012, 12, 16522.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. S. T. Whitten, B. García-Moreno E. and V. J. Hilser, Local conformational fluctuations can modulate the coupling between proton binding and global structural transitions in proteins, Proc. Natl. Acad. Sci. U. S. A., 2005, 102, 4282–4287.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. J. R. Griffiths, Are cancer cells acidic?, Br. J. Cancer, 1991, 64, 425–427.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. L. Yuan, W. Lin, K. Zheng, L. He and W. Huang, Far-red to near infrared analyte-responsive fluorescent probes based on organic fluorophore platforms for fluorescence imaging, Chem. Soc. Rev., 2013, 42, 622–661.

    Article  CAS  PubMed  Google Scholar 

  6. T. Terai and T. Nagano, Fluorescent probes for bioimaging applications, Curr. Opin. Chem. Biol., 2008, 12, 515–521.

    Article  CAS  PubMed  Google Scholar 

  7. J. E. Whitaker, R. P. Haugland and F. G. Prendergast, Spectral and photophysical studies of benzo[c]xanthene dyes: Dual emission pH sensors, Anal. Biochem., 1991, 194, 330–344.

    Article  CAS  PubMed  Google Scholar 

  8. J. Han and K. Burgess, Fluorescent Indicators for Intracellular pH, Chem. Rev., 2010, 110, 2709–2728.

    Article  CAS  PubMed  Google Scholar 

  9. H. Koo, M. S. Huh, J. H. Ryu, D.-E. Lee, I.-C. Sun, K. Choi, K. Kim and I. C. Kwon, Nanoprobes for biomedical imaging in living systems, Nano Today, 2011, 6, 204–220.

    Article  CAS  Google Scholar 

  10. N. Hildebrandt, C. M. Spillmann, W. R. Algar, T. Pons, M. H. Stewart, E. Oh, K. Susumu, S. A. Díaz, J. B. Delehanty and I. L. Medintz, Energy Transfer with Semiconductor Quantum Dot Bioconjugates: A Versatile Platform for Biosensing, Energy Harvesting, and Other Developing Applications, Chem. Rev., 2017, 117, 536–711.

    Article  CAS  PubMed  Google Scholar 

  11. S. Sharifi, S. Behzadi, S. Laurent, M. Laird Forrest, P. Stroeve and M. Mahmoudi, Toxicity of nanomaterials, Chem. Soc. Rev., 2012, 41, 2323–2343.

    Article  CAS  PubMed  Google Scholar 

  12. S. Bonacchi, D. Genovese, R. Juris, M. Montalti, L. Prodi, E. Rampazzo and N. Zaccheroni, Luminescent Silica Nanoparticles: Extending the Frontiers of Brightness, Angew. Chem., Int. Ed., 2011, 50, 4056–4066.

    Article  CAS  Google Scholar 

  13. S. W. Bae, W. Tan and J.-I. Hong, Fluorescent dye-doped silica nanoparticles: new tools for bioapplications, Chem. Commun., 2012, 48, 2270–2282.

    Article  CAS  Google Scholar 

  14. C. Li and S. Liu, Polymeric assemblies and nanoparticles with stimuli-responsive fluorescence emission characteristics, Chem. Commun., 2012, 48, 3262–3278.

    Article  CAS  Google Scholar 

  15. T. Doussineau, A. Schulz, A. Lapresta-Fernandez, A. Moro, S. Körsten, S. Trupp and G. J. Mohr, On the Design of Fluorescent Ratiometric Nanosensors, Chem. – Eur. J., 2010, 16, 10290–10299.

    Article  CAS  PubMed  Google Scholar 

  16. H. Sun, K. Almdal and T. L. Andresen, Expanding the dynamic measurement range for polymeric nanoparticle pH sensors, Chem. Commun., 2011, 47, 5268–5270.

    Article  CAS  Google Scholar 

  17. R. V. Benjaminsen, H. Sun, J. R. Henriksen, N. M. Christensen, K. Almdal and T. L. Andresen, Evaluating Nanoparticle Sensor Design for Intracellular pH Measurements, ACS Nano, 2011, 5, 5864–5873.

    Article  CAS  PubMed  Google Scholar 

  18. E. Allard and C. Larpent, Core-shell type dually fluorescent polymer nanoparticles for ratiometric pH-sensing, J. Polym. Sci., Part A: Polym. Chem., 2008, 46, 6206–6213.

    Article  CAS  Google Scholar 

  19. S. Hornig, C. Biskup, A. Gräfe, J. Wotschadlo, T. Liebert, G. J. Mohr and T. Heinze, Biocompatible fluorescent nanoparticles for pH-sensoring, Soft Matter, 2008, 4, 1169–1172.

    Article  CAS  PubMed  Google Scholar 

  20. A. Schulz, J. Wotschadlo, T. Heinze and G. J. Mohr, Fluorescent nanoparticles for ratiometric pH-monitoring in the neutral range, J. Mater. Chem., 2010, 20, 1475–1482.

    Article  CAS  Google Scholar 

  21. H. Sun, A. M. Scharff-Poulsen, H. Gu and K. Almdal, Synthesis and Characterization of Ratiometric, pH Sensing Nanoparticles with Covalently Attached Fluorescent Dyes, Chem. Mater., 2006, 18, 3381–3384.

    Article  CAS  Google Scholar 

  22. C. Li, Y. Zhang, J. Hu, J. Cheng and S. Liu, Reversible Three-State Switching of Multicolor Fluorescence Emission by Multiple Stimuli Modulated FRET Processes within Thermoresponsive Polymeric Micelles, Angew. Chem., Int. Ed., 2010, 49, 5120–5124.

    Article  CAS  Google Scholar 

  23. K. Ouadahi, K. Sbargoud, E. Allard and C. Larpent, FRET-mediated pH-responsive dual fluorescent nanoparticles prepared via click chemistry, Nanoscale, 2012, 4, 727–732.

    Article  CAS  PubMed  Google Scholar 

  24. H.-s. Peng, J. A. Stolwijk, L.-N. Sun, J. Wegener and O. S. Wolfbeis, A Nanogel for Ratiometric Fluorescent Sensing of Intracellular pH Values, Angew. Chem., Int. Ed., 2010, 49, 4246–4249.

    Article  CAS  Google Scholar 

  25. J. Chen, Y. Tang, H. Wang, P. Zhang, Y. Li and J. Jiang, Design and fabrication of fluorescence resonance energy transfer-mediated fluorescent polymer nanoparticles for ratiometric sensing of lysosomal pH, J. Colloid Interface Sci., 2016, 484, 298–307.

    Article  CAS  PubMed  Google Scholar 

  26. P. Zhang, H. Wang, Y. Hong, M. Yu, R. Zeng, Y. Long and J. Chen, Selective visualization of endogenous hypochlorous acid in zebrafish during lipopolysaccharide-induced acute liver injury using a polymer micelles-based ratiometric fluorescent probe, Biosens. Bioelectron., 2018, 99, 318–324.

    Article  CAS  PubMed  Google Scholar 

  27. M. Ryvolova, J. Chomoucka, J. Drbohlavova, P. Kopel, P. Babula, D. Hynek, V. Adam, T. Eckschlager, J. Hubalek, M. Stiborova, J. Kaiser and R. Kizek, Modern micro and nanoparticle-based imaging techniques, Sensors, 2012, 12, 14792–14820.

    Article  PubMed  PubMed Central  Google Scholar 

  28. C. Grazon, J. Rieger, R. Méallet-Renault, G. Clavier and B. Charleux, One-Pot Synthesis of Pegylated Fluorescent Nanoparticles by RAFT Miniemulsion Polymerization Using a Phase Inversion Process, Macromol. Rapid Commun., 2011, 32, 699–705.

    Article  CAS  PubMed  Google Scholar 

  29. C. Grazon, J. Rieger, R. Méallet-Renault, B. Charleux and G. Clavier, Ultrabright Fluorescent Polymeric Nanoparticles Made from a New Family of BODIPY Monomers, Macromolecules, 2013, 46, 5167–5176.

    Article  CAS  Google Scholar 

  30. R. Sjöback, J. Nygren and M. Kubista, Absorption and fluorescence properties of fluorescein, Spectrochim. Acta, Part A, 1995, 51, L7–L21.

  31. C. Munkholm, D. R. Parkinson and D. R. Walt, Intramolecular fluorescence self-quenching of fluoresceinamine, J. Am. Chem. Soc., 1990, 112, 2608–2612.

    Article  CAS  Google Scholar 

  32. D. H. Ma, D. Kim, T. Akisawa, K.-H. Lee, K.-T. Kim and K. H. Ahn, An FITC-BODIPY FRET Couple: Application to Selective, Ratiometric Detection and Bioimaging of Cysteine, Chem. – Asian J., 2015, 10, 894–902.

    Article  CAS  PubMed  Google Scholar 

  33. L. Couvreur, C. Lefay, J. Belleney, B. Charleux, O. Guerret and S. Magnet, First Nitroxide-Mediated Controlled Free-Radical Polymerization of Acrylic Acid, Macromolecules, 2003, 36, 8260–8267.

    Article  CAS  Google Scholar 

  34. R. Birge, Kodak laser dyes, Eastman Kodak Company, Rochester, NY, 1987.

  35. B. Valeur and M. N. Berberan-Santos, Molecular fluorescence: principles and applications, John Wiley & Sons, 2012.

  36. S. Boissé, J. Rieger, K. Belal, A. Di-Cicco, P. Beaunier, M.-H. Li and B. Charleux, Amphiphilic block copolymer nano-fibers via RAFT-mediated polymerization in aqueous dispersed system, Chem. Commun., 2010, 46, 1950–1952.

    Article  Google Scholar 

  37. C. Grazon, J. Rieger, P. Beaunier, R. Méallet-Renault and G. Clavier, Fluorescent core–shell nanoparticles and nanocapsules using comb-like macromolecular RAFT agents: synthesis and functionalization thereof, Polym. Chem., 2016, 7, 4272–4283.

    Article  CAS  Google Scholar 

  38. J. B. McLeary and B. Klumperman, RAFT mediated polymerisation in heterogeneous media, Soft Matter, 2006, 2, 45–53.

    Article  CAS  PubMed  Google Scholar 

  39. P. B. Zetterlund, Y. Kagawa and M. Okubo, Controlled/Living Radical Polymerization in Dispersed Systems, Chem. Rev., 2008, 108, 3747–3794.

    Article  CAS  PubMed  Google Scholar 

  40. Y. Si, C. Grazon, G. Clavier, J. Rieger, J.-F. Audibert, B. Sclavi and R. Méallet-Renault, Rapid and accurate detection of Escherichia coli growth by fluorescent pH-sensitive organic nanoparticles for high-throughput screening applications, Biosens. Bioelectron., 2016, 75, 320–327.

    Article  CAS  PubMed  Google Scholar 

  41. C. A. G. N. Montalbetti and V. Falque, Amide bond formation and peptide coupling, Tetrahedron, 2005, 61, 10827–10852.

    Article  CAS  Google Scholar 

  42. F. A. Tobiesen and S. Michielsen, Method for grafting poly (acrylic acid) onto nylon 6,6 using amine end groups on nylon surface, J. Polym. Sci., Part A: Polym. Chem., 2002, 40, 719–728.

    Article  CAS  Google Scholar 

  43. S. Yang, X. Yu, L. Wang, Y. Tu, J. X. Zheng, J. Xu, R. M. Van Horn and S. Z. D. Cheng, Hydrogen-Bonding-Driven Complexation of Polystyrene-block-poly(ethylene oxide) Micelles with Poly(acrylic acid), Macromolecules, 2010, 43, 3018–3026.

    Article  CAS  Google Scholar 

  44. A. Ranjan, N. Pothayee, M. Seleem, N. Jain, N. Sriranganathan, J. S. Riffle and R. Kasimanickam, Drug delivery using novel nanoplexes against a Salmonella mouse infection model, J. Nanopart. Res., 2010, 12, 905–914.

    Article  CAS  Google Scholar 

  45. M. Carvell, I. D. Robb and P. W. Small, The influence of labelling mechanisms on the fluorescence behaviour of polymers bearing fluorescein labels, Polymer, 1998, 39, 393–398.

    Article  CAS  Google Scholar 

  46. C. Déjugnat, D. Haložan and G. B. Sukhorukov, Defined Picogram Dose Inclusion and Release of Macromolecules using Polyelectrolyte Microcapsules, Macromol. Rapid Commun., 2005, 26, 961–967.

    Article  CAS  Google Scholar 

  47. A. Reisch and A. S. Klymchenko, Fluorescent Polymer Nanoparticles Based on Dyes: Seeking Brighter Tools for Bioimaging, Small, 2016, 12, 1968–1992.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. G. Sun, M. Y. Berezin, J. Fan, H. Lee, J. Ma, K. Zhang, K. L. Wooley and S. Achilefu, Bright fluorescent nanoparticles for developing potential optical imaging contrast agents, Nanoscale, 2010, 2, 548–558.

    Article  CAS  PubMed  Google Scholar 

  49. R. Méallet-Renault, A. Hérault, J.-J. Vachon, R. B. Pansu, S. Amigoni-Gerbier and C. Larpent, Fluorescent nanoparticles as selective Cu(ii) sensors, Photochem. Photobiol. Sci., 2006, 5, 300–310.

    Article  PubMed  Google Scholar 

  50. U. Resch-Genger, M. Grabolle, S. Cavaliere-Jaricot, R. Nitschke and T. Nann, Quantum dots versus organic dyes as fluorescent labels, Nat. Methods, 2008, 5, 763.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. PPSM, ENS Cachan, CNRS, Université Paris-Saclay, 94235, Cachan, France

    Chloé Grazon, Yang Si, Jean-Pierre Placial, Rachel Méallet-Renault & Gilles Clavier

  2. Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire, UMR 8232, Team: Chimie des Polymères, 75005, Paris, France

    Jutta Rieger

  3. Laboratoire de Chimie des Polymères Organiques (LCPO), CNRS UMR 5629, Université de Bordeaux, Bordeaux-INP, Pessac, 33607, Cedex, France

    Chloé Grazon

  4. Institut des Sciences Moléculaires d’Orsay (ISMO), CNRS, Univ. Paris-Sud, Université Paris-Saclay, F-91405, Orsay, France

    Rachel Méallet-Renault

Authors
  1. Chloé Grazon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yang Si
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jean-Pierre Placial
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jutta Rieger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rachel Méallet-Renault
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gilles Clavier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chloé Grazon.

Additional information

Electronic supplementary information (ESI) available: Additional equations, scheme of the synthesis of FNP, additional characterizations of FNP (including TEM images), additional absorption and emission spectra of FNP and calibrations curves. See DOI: 10.1039/c8pp00457a

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Grazon, C., Si, Y., Placial, JP. et al. Core–shell polymeric nanoparticles comprising BODIPY and fluorescein as ultra-bright ratiometric fluorescent pH sensors. Photochem Photobiol Sci 18, 1156–1165 (2019). https://doi.org/10.1039/c8pp00457a

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1039/c8pp00457a

Search

Navigation