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A fluorescent nanoprobe for real-time monitoring of intracellular singlet oxygen during photodynamic therapy

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Abstract

Sensing of intracellular singlet oxygen (1O2) is required in order to optimize photodynamic therapy (PDT). An optical nanoprobe is reported here for the optical determination of intracellular 1O2. The probe consists of a porous particle core doped with the commercial 1O2 probe 1,3-diphenylisobenzofuran (DPBF) and a layer of poly-L-lysine. The nanoparticle probes have a particle size of ~80 nm in diameter, exhibit good biocompatibility, improved photostability and high sensitivity for 1O2 in both absorbance (peak at 420 nm) and fluorescence (with excitation/emission peaks at 405/458 nm). Nanoprobes doped with 20% of DPBF are best suited even though they suffer from concentration quenching of fluorescence. In comparison with the commercial fluorescent 1O2 probe SOSG, 20%-doped DPBF-NPs (aged) shows higher sensitivity for 1O2 generated at an early stage. The best nanoprobes were used to real-time monitor the PDT-triggered generation of 1O2 inside live cells, and the generation rate is found to depend on the supply of intracellular oxygen.

A fluorescent nanoprobe featured with refined selectivity and improved sensitivity towards 1O2 was prepared from the absorption-based probe DBPF and used to real-time monitoring of the generation of intracellular 1O2 produced during PDT.

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References

  1. Sanabria LM, Rodríguez ME, Cogno IS, Vittar NBR, Pansa MF, Lamberti MJ et al (2013) Direct and indirect photodynamic therapy effects on the cellular and molecular components of the tumor microenvironment. Biochimica et Biophysica Acta (BBA)-reviews on. Cancer 1835:36–45

    Google Scholar 

  2. Dolmans DE, Fukumura D, Jain RK (2003) Photodynamic therapy for cancer. Nat Rev Cancer 3:380–387

    Article  CAS  PubMed  Google Scholar 

  3. Vaupel P, Mayer A (2007) Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev 26:225–239

    Article  CAS  PubMed  Google Scholar 

  4. Busch TM, Xing X, Yu G, Yodh A, Wileyto EP, Wang H-W, Durduran T, Zhu TC, Wang KKH (2009) Fluence rate-dependent intratumor heterogeneity in physiologic and cytotoxic responses to Photofrin photodynamic therapy. Photochem Photobiol Sci 8:1683–1693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Niedre M, Patterson MS, Wilson BC (2002) Direct near-infrared luminescence detection of singlet oxygen generated by photodynamic therapy in cells in vitro and tissues in vivo¶. Photochem Photobiol 75:382–391

    Article  CAS  PubMed  Google Scholar 

  6. da Silva EF, Pedersen BW, Breitenbach T, Toftegaard R, Kuimova MK, Arnaut LG et al (2011) Irradiation-and sensitizer-dependent changes in the lifetime of intracellular singlet oxygen produced in a photosensitized process. J Phys Chem B 116:445–461

    Article  CAS  PubMed  Google Scholar 

  7. Celli JP, Spring BQ, Rizvi I, Evans CL, Samkoe KS, Verma S, Pogue BW, Hasan T (2010) Imaging and photodynamic therapy: mechanisms, monitoring, and optimization. Chem Rev 110:2795–2838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Schlothauer J, Hackbarth S, Röder B (2008) A new benchmark for time-resolved detection of singlet oxygen luminescence–revealing the evolution of lifetime in living cells with low dose illumination. Laser Phys Lett 6:216

    Article  CAS  Google Scholar 

  9. Scholz M, Dědic R, Hála J (2017) Microscopic time-resolved imaging of singlet oxygen by delayed fluorescence in living cells. Photochem Photobiol Sci 16:1643–1653

    Article  CAS  PubMed  Google Scholar 

  10. Chen X, Wang F, Hyun JY, Wei T, Qiang J, Ren X, Shin I, Yoon J (2016) Recent progress in the development of fluorescent, luminescent and colorimetric probes for detection of reactive oxygen and nitrogen species. Chem Soc Rev 45:2976–3016

    Article  CAS  PubMed  Google Scholar 

  11. Wang H-S (2016) Development of fluorescent and luminescent probes for reactive oxygen species. TrAC Trends Anal Chem 85:181–202

    Article  CAS  Google Scholar 

  12. Flors C, Fryer MJ, Waring J, Reeder B, Bechtold U, Mullineaux PM, Nonell S, Wilson MT, Baker NR (2006) Imaging the production of singlet oxygen in vivo using a new fluorescent sensor, singlet oxygen sensor green®. J Exp Bot 57:1725–1734

    Article  CAS  PubMed  Google Scholar 

  13. Lin H, Shen Y, Chen D, Lin L, Wilson BC, Li B, Xie S (2013) Feasibility study on quantitative measurements of singlet oxygen generation using singlet oxygen sensor green. J Fluoresc 23:41–47

    Article  CAS  PubMed  Google Scholar 

  14. Ragàs X, Jiménez-Banzo A, Sánchez-García D, Batllori X, Nonell S (2009) Singlet oxygen photosensitisation by the fluorescent probe singlet oxygen sensor green®. Chem Commun:2920–2922

  15. Gollmer A, Arnbjerg J, Blaikie FH, Pedersen BW, Breitenbach T, Daasbjerg K, Glasius M, Ogilby PR (2011) Singlet oxygen sensor green®: photochemical behavior in solution and in a mammalian cell. Photochem Photobiol 87:671–679

    Article  CAS  PubMed  Google Scholar 

  16. Kim S, Fujitsuka M, Majima T (2013) Photochemistry of singlet oxygen sensor green. J Phys Chem B 117:13985–13992

    Article  CAS  PubMed  Google Scholar 

  17. Ruiz-González R, Bresolí-Obach R, Gulías Ò, Agut M, Savoie H, Boyle RW et al (2017) NanoSOSG: a nanostructured fluorescent probe for the detection of intracellular singlet oxygen. Angew Chem Int Ed 56:2931–2934

    Article  Google Scholar 

  18. Pedersen SK, Holmehave J, Blaikie FH, Gollmer A, Breitenbach T, Jensen HH, Ogilby PR (2014) Aarhus sensor green: a fluorescent probe for singlet oxygen. J Org Chem 79:3079–3087

    Article  CAS  PubMed  Google Scholar 

  19. Dai Z, Tian L, Xiao Y, Ye Z, Zhang R, Yuan J (2013) A cell-membrane-permeable europium complex as an efficient luminescent probe for singlet oxygen. J Mater Chem B 1:924–927

    Article  CAS  Google Scholar 

  20. Song D, Cho S, Han Y, You Y, Nam W (2013) Ratiometric fluorescent probes for detection of intracellular singlet oxygen. Org Lett 15:3582–3585

    Article  CAS  PubMed  Google Scholar 

  21. Yuan Y, Zhang C-J, Xu S, Liu B (2016) A self-reporting AIE probe with a built-in singlet oxygen sensor for targeted photodynamic ablation of cancer cells. Chem Sci 7:1862–1866

    Article  CAS  PubMed  Google Scholar 

  22. Kim S, Tachikawa T, Fujitsuka M, Majima T (2014) Far-red fluorescence probe for monitoring singlet oxygen during photodynamic therapy. J Am Chem Soc 136:11707–11715

    Article  CAS  PubMed  Google Scholar 

  23. Liu H-W, Xu S, Wang P, Hu X-X, Zhang J, Yuan L, Zhang XB, Tan W (2016) An efficient two-photon fluorescent probe for monitoring mitochondrial singlet oxygen in tissues during photodynamic therapy. Chem Commun 52:12330–12333

    Article  CAS  Google Scholar 

  24. Ping J-T, Peng H-S, Duan W-B, You F-T, Song M, Wang Y-Q (2016) Synthesis and optimization of ZnPc-loaded biocompatible nanoparticles for efficient photodynamic therapy. J Mater Chem B 4:4482–4489

    Article  CAS  Google Scholar 

  25. Jenie SA, Plush SE, Voelcker NH (2017) Singlet oxygen detection on a nanostructured porous silicon thin film via photonic luminescence enhancements. Langmuir 33:8606–8613

    Article  CAS  PubMed  Google Scholar 

  26. Frausto F, Thomas SW III (2017) Ratiometric singlet oxygen detection in water using acene-doped conjugated polymer nanoparticles. ACS Appl Mater Interfaces 9:15768–15775

    Article  CAS  PubMed  Google Scholar 

  27. Gao J, Wang C, Tan H (2017) Dual-emissive polystyrene@zeolitic imidazolate framework-8 composite for ratiometric detection of singlet oxygen. J Mater Chem B 5:9175–9182

    Article  CAS  Google Scholar 

  28. Tanielian C, Schweitzer C, Mechin R, Wolff C (2001) Quantum yield of singlet oxygen production by monomeric and aggregated forms of hematoporphyrin derivative. Free Radic Biol Med 30:208–212

    Article  CAS  PubMed  Google Scholar 

  29. Aubry J-M, Pierlot C, Rigaudy J, Schmidt R (2003) Reversible binding of oxygen to aromatic compounds. Acc Chem Res 36:668–675

    Article  CAS  PubMed  Google Scholar 

  30. Zhang X-F, Li X (2011) The photostability and fluorescence properties of diphenylisobenzofuran. J Lumin 131:2263–2266

    Article  CAS  Google Scholar 

  31. Adams DR, Wilkinson F (1972) Lifetime of singlet oxygen in liquid solution. J Chem Soc Faraday Trans 2: Mol Chem Phys 68:586–593

    Article  CAS  Google Scholar 

  32. Wozniak M, Tanfani F, Bertoli E, Zolese G, Antosiewicz J (1991) A new fluorescence method to detect singlet oxygen inside phospholipid model membranes. Biochim Biophys Acta 1082:94–100

    Article  CAS  PubMed  Google Scholar 

  33. Peng H-S, Chiu DT (2015) Soft fluorescent nanomaterials for biological and biomedical imaging. Chem Soc Rev 44:4699–4722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Gomes A, Fernandes E, Lima JLFC (2005) Fluorescence probes used for detection of reactive oxygen species. J Biochem Biophys Methods 65:45–80

    Article  CAS  PubMed  Google Scholar 

  35. Wang XH, Peng HS, Yang L, You FT, Teng F, Hou LL, Wolfbeis OS (2014) Targetable phosphorescent oxygen nanosensors for the assessment of tumor mitochondrial dysfunction by monitoring the respiratory activity. Angew Chem 126:12679–12683

    Article  Google Scholar 

  36. Kuimova MK, Yahioglu G, Ogilby PR (2009) Singlet oxygen in a cell: spatially dependent lifetimes and quenching rate constants. J Am Chem Soc 131:332–340

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was financially supported by the NSFC (Grants 61775245, 61627814, 61675238) and the MUC 111 project.

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Authors and Affiliations

  1. School of Science, Minzu University of China, Beijing, 100081, China

    Jian-tao Ping, Hong-shang Peng, Jinglei Qin, Yi-quan Wang, Gen-xiang Chen & Min Song

  2. Key Laboratory of Luminescence and Optical Information, Ministry of Education, Institute of Optoelectronic Technology, Beijing Jiaotong University, Beijing, 100044, China

    Jian-tao Ping & Fang-tian You

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  1. Jian-tao Ping
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  2. Hong-shang Peng
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Correspondence to Hong-shang Peng.

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Ping, Jt., Peng, Hs., Qin, J. et al. A fluorescent nanoprobe for real-time monitoring of intracellular singlet oxygen during photodynamic therapy. Microchim Acta 185, 269 (2018). https://doi.org/10.1007/s00604-018-2815-5

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