Microchimica Acta

, 186:842 | Cite as

Polylysine modified conjugated polymer nanoparticles loaded with the singlet oxygen probe 1,3-diphenylisobenzofuran and the photosensitizer indocyanine green for use in fluorometric sensing and in photodynamic therapy

  • Xiao-hui WangEmail author
  • Yin-xiao Yu
  • Kun Cheng
  • Wei Yang
  • Yuan-an Liu
  • Hong-shang PengEmail author
Original Paper


Conjugated polymer hybrid nanoparticles (NPs) loaded with both indocyanine green (ICG) and 1,3-diphenylisobenzofuran (DPBF) are described. The NPs are dually functional in that ICG acts as the photosensitizer, and DPBF as a probe for singlet oxygen (1O2 probe). The nanoparticle core consists of the energy donating host poly(9,9-dioctylfluorenyl-2,7-diyl)-co-(2,5-p-xylene) (PFP). The polymer is doped with the energy acceptor DPBF. Ratiometric fluorometric detection of singlet oxygen is accomplished by measurement of fluorescence at wavelengths of 415 and 458 nm. In addition, the shell of the positively charged polymeric nanoparticles was modified, via electrostatic interaction, with negatively charged PDT drugs ICG. The integrated nanoparticles of type ICG-DPBF-PFP display effective photodynamic performance under 808-nm laser irradiation. The 1O2 sensing behaviors of samples are evaluated based on the ratiometric fluorescent responses produced by DPBF and PFP. 1O2 can be fluorimetically sensed with a detection limit of 28 μM. The multifunctional nanoprobes exhibit effortless cellular uptake, superior photodynamic activity and a rapid ratiometric response to 1O2.

Graphical abstract

Schematic of a dual-functional nanoplatform for photodynamic therapy (PDT) and singlet oxygen (1O2) feedback. It offers a new strategy for self-monitoring photodynamic ablation. FRET: fluorescence resonance energy transfer. Indocyanine green is attached in the shell of nanoparticles, and 1,3-diphenylisobenzofuran is doped into the energy donating host conjugated polymer.


Singlet oxygen detection Photodynamic effects DPBF Ratiometric assay Fluorescent probe 



This work was financially supported from the National Nature Science Foundation of China (Grant No. 61605014, 61775245 and 61821001), and the Fundamental Research Funds for the Central Universities (Grant No. 2018RC18 and 2018RC17).

Supplementary material

604_2019_3924_MOESM1_ESM.docx (408 kb)
ESM 1 (DOCX 408 kb)


  1. 1.
    Dolmans DE, Fukumura D, Jain RK (2003) Photodynamic therapy for Cancer. Nat Rev Cancer 3:380–387CrossRefGoogle Scholar
  2. 2.
    Cai Y, Liang P, Tang Q, Yang X, Si W, Huang W, Zhang Q, Dong X (2017) Diketopyrrolopyrrole-Triphenylamine organic nanoparticles as multifunctional reagents for Photoacoustic imaging-guided photodynamic/Photothermal synergistic tumor therapy. ACS Nano 11:1054–1063CrossRefGoogle Scholar
  3. 3.
    Ethirajan M, Chen Y, Joshi P, Pandey RK (2011) The role of Porphyrin chemistry in tumor imaging and photodynamic therapy. Chem Soc Rev 40:340–362CrossRefGoogle Scholar
  4. 4.
    Ding H, Cai YJ, Chen JX, Lu T, Wen WP, Nie GH, Wang XJ (2019) Cryodesiccation-driven crystallization preparation approach for zinc(II)-phthalocyanine nanodots in cancer photodynamic therapy and photoacoustic imaging. Microchim Acta 186:237–244CrossRefGoogle Scholar
  5. 5.
    Clement S, Chen W, Anwer AG, Goldys EM (2017) Verteprofin conjugated to gold nanoparticles for fluorescent cellular bioimaging and X-ray mediated photodynamic therapy. Microchim Acta 184:1765–1771CrossRefGoogle Scholar
  6. 6.
    Wang H, Li X, Tse BW (2018) Indocyanine green-incorporating nanoparticles for cancer theranostics. Theranostics 8:1227–1242CrossRefGoogle Scholar
  7. 7.
    Hu H, Chen J, Yang H, Huang X, Wu H, Wu Y, Li F, Yi Y, Xiao C, Li Y, Tang Y, Li Z, Zhang B, Yang X (2019) Potentiating photodynamic therapy of ICG-loaded nanoparticles by depleting GSH with PEITC. Nanoscale 11:6384–6393CrossRefGoogle Scholar
  8. 8.
    Tang Y, Chen H, Chang K, Liu Z, Wang Y, Qu S, Xu H, Wu C (2017) Photocrosslinkable polymer dots with stable sensitizer loading and amplified singlet oxygen generation for photodynamic therapy. ACS Appl Mater Interfaces 9:3419–3431CrossRefGoogle Scholar
  9. 9.
    Chen R, Wang X, Yao X, Zheng X, Wang J, Jiang X (2013) Near-IR-triggered photothermal/photodynamic dual-modality therapy system via chitosan hybrid nanospheres. Biomaterials 34:8314–8322CrossRefGoogle Scholar
  10. 10.
    Barth BM, Altinoglu E, Shanmugavelandy SS, Kaiser JM, Crespo-Gonzalez D, DiVittore NA, McGovern C, Goff TM, Keasey NR, Adair JH, Loughran TP, Claxton DF, Kester M (2011) Targeted Indocyanine-green-loaded calcium Phosphosilicate nanoparticles for in vivo photodynamic therapy of leukemia. ACS Nano 5:5325–5337CrossRefGoogle Scholar
  11. 11.
    Vaupel P, Mayer A (2007) Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev 26:225–239CrossRefGoogle Scholar
  12. 12.
    Kim J, Cho HR, Jeon H, Kim D, Song C, Lee N, Choi SH, Hyeon T (2017) Continuous O2-evolving MnFe2O4 nanoparticle-anchored Mesoporous silica nanoparticles for efficient photodynamic therapy in hypoxic Cancer. J Am Chem Soc 139:10992–10995CrossRefGoogle Scholar
  13. 13.
    Sharma BR (2007) Infection in patients with severe burns: causes and prevention thereof. Infect Dis Clin N Am 21:745–759CrossRefGoogle Scholar
  14. 14.
    Zhang P, Steelant W, Kumar M, Scholfield M (2007) Versatile photosensitizers for photodynamic therapy at infrared excitation. J Am Chem Soc 129:4526–4527CrossRefGoogle Scholar
  15. 15.
    Yan F, Kopelman R (2003) The embedding of Meta-tetra(Hydroxyphenyl)-Chlorin into silica nanoparticle platforms for photodynamic therapy and their singlet oxygen production and pH-dependent optical properties. Photochem Photobiol 78:587–591CrossRefGoogle Scholar
  16. 16.
    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 75:382–391CrossRefGoogle Scholar
  17. 17.
    Schweitzer C, Schmidt R (2003) Physical mechanisms of generation and deactivation of singlet oxygen. Chem Rev 103:1685–1757CrossRefGoogle Scholar
  18. 18.
    Kim S, Fujitsuka M, Majima T (2003) Photochemistry of singlet oxygen sensor green. J Phys Chem B 117:13985–13992CrossRefGoogle Scholar
  19. 19.
    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 87:671–679CrossRefGoogle Scholar
  20. 20.
    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 45:2976–3016CrossRefGoogle Scholar
  21. 21.
    Bresolí-Obach R, Nos J, Mora M, Sagristà ML, Ruiz-González R, Nonell S (2016) Anthracene-based fluorescent nanoprobes for singlet oxygen detection in biological media. Methods 109:64–72CrossRefGoogle Scholar
  22. 22.
    Frausto F, Thomas SW (2017) Ratiometric singlet oxygen detection in water using acene-doped conjugated polymer nanoparticles. ACS Appl Mater Interfaces 9:15768–15775CrossRefGoogle Scholar
  23. 23.
    Zhang J, Sarrafpour S, Pawle RH, Thomas SW (2011) Acene-linked conjugated polymers with ratiometric fluorescent responsebto 1O2. Chem Commun 47:3445–3447CrossRefGoogle Scholar
  24. 24.
    Ping J, Peng H, Qin J, You F, Wang Y, Chen G, Song M (2018) A fluorescent nanoprobe for real-time monitoring of intracellular singlet oxygen during photodynamic therapy. Microchim Acta 185:269–277CrossRefGoogle Scholar
  25. 25.
    Zhang XF, Li X (2011) The photostability and fluorescence properties of diphenylisobenzofuran. J Lumin 131:2263–2266CrossRefGoogle Scholar
  26. 26.
    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 5:9175–9182CrossRefGoogle Scholar
  27. 27.
    Zhang T, Li Y, Zheng Z, Ye R, Zhang Y, Kwok RTK, Lam JWY, Tang BZ (2019) In-situ monitoring apoptosis process by a self-reporting photosensitizer. J Am Chem Soc 14:5612–5616. CrossRefGoogle Scholar
  28. 28.
    Suo H, Zhao X, Zhang Z, Wu Y, Guo C (2018) Up-converting LuVO4: Nd3+/Yb3+/Er3+@SiO2@Cu2S hollow Nanoplatforms for self-monitored Photothermal ablation. ACS Appl Mater Interfaces 10:39912–39920CrossRefGoogle Scholar
  29. 29.
    Zhu X, Feng W, Chang J, Tan Y, Li J, Chen M, Sun Y, Li F (2016) Temperature-feedback upconversion nanocomposite for accurate photothermal therapy at facile temperature. Nat Commun 7:10437–10446CrossRefGoogle Scholar
  30. 30.
    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 Int Ed 126:12679–12683CrossRefGoogle Scholar
  31. 31.
    Wang XH, Peng HS, Yang W, Ren ZD, Liu XM, Liu YA (2017) Indocyanine green-platinum porphyrins integrated conjugated polymer hybrid nanoparticles for near-infrared-triggered photothermal and two-photon photodynamic therapy. J Mater Chem B 5:1856–1862CrossRefGoogle Scholar
  32. 32.
    Wang X, Meier RJ, Schäferling M, Bange S, Lupton JM, Sperber M, Wegener J, Ondrus V, Beifuss U, Henne U, Klein C, Wolfbeis OS (2016) Two-photon excitation temperature nanosensors based on a conjugated fluorescent polymer doped with a europium probe. Adv Opt Mater 4:1854–1859CrossRefGoogle Scholar
  33. 33.
    Thomas AP, Saneesh Babu PS, Asha Nair S, Ramakrishnan S, Ramaiah D, Chandrashekar TK, Srinivasan A, Radhakrishna Pillai M (2012) Meso-tetrakis(p-sulfonatophenyl) N-confused Porphyrin Tetrasodium salt: a potential sensitizer for photodynamic therapy. J Med Chem 55:5110–5120CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Beijing Key Laboratory of Work Safety Intelligent Monitoring, School of Electronic EngineeringBeijing University of Posts and TelecommunicationsBeijingChina
  2. 2.School of ScienceMinzu University of ChinaBeijingChina

Personalised recommendations