Microchimica Acta

, Volume 184, Issue 6, pp 1765–1771 | Cite as

Verteprofin conjugated to gold nanoparticles for fluorescent cellular bioimaging and X-ray mediated photodynamic therapy

  • Sandhya Clement
  • Wenjie Chen
  • Ayad G. Anwer
  • Ewa M. Goldys
Original Paper

Abstract

Photodynamic therapy (PDT) uses photosensitizers, light and molecular oxygen to generate cytotoxic reactive oxygen species. Its effectiveness is limited to <1 cm due to the limited penetration depth of light. The present study compares the PDT effectivity of the photosensitizer verteporfin (VP) conjugated to gold nanoparticles (AuNPs) (a) by using deeply penetrating X-rays administered in standard radiotherapy doses, and (b) by using red light (690 nm). VP was conjugated to AuNPs of around 12 nm size to enhance the interaction of ionizing radiation with PS. For comparison, VP also was directly exposed to X-rays. It is found that VP alone is stimulated by X-rays to generate singlet oxygen. The conjugate to AuNPs also generated a significant amount of singlet oxygen on irradiation with X-rays in comparison to illumination with 690-nm light. It is also found that the rate of singlet oxygen generation is amplified in case of AuNP-conjugated VP compared to VP alone. The performance of the AuNP-VP conjugate and of the VP alone was tested in Panc 1 cells. Their viability was impaired much more in these two scenarios than with the X-ray radiation only. This suggests excellent perspectives for PDT based on VP and with X-ray stimulation, both as a stand-alone photosensitizer and in Au-NP conjugates. Moreover, both VP and AuNP-VP conjugates show bright fluorescence in physiological media for excitation/emission wavelengths in the range of 405/690 nm; hence they can also be used for simultaneous bioimaging.

Graphical abstract

Pancreatic cancer cells (Panc 1) administered with gold nanoparticle- verteporfin conjugate (AuNP-VP) showed an efficient cell killing effect with the generation of singlet oxygen (1O2 ) from triplet oxygen (3O2 ) under 690 nm irradiation and X-ray radiation.

Keywords

PDT Photosensitizer Gold nanoparticle X-ray Bioimaging Fluorescence SOSG probe Singlet oxygen Cell uptake Cell toxicity 

Notes

Acknowledgements

The authors thank Mr. Vaughan Moutrie and Mr. Daniel Santos from Genesis Cancer Care for helping us with X-ray radiation experiment. All fluorescence measurements were performed in the Optical Characterization Facility, Linked Laboratory to AMMRF (Australian Microscopy and Microanalysis Research Facility). Authors Sandhya Clement and Wenjie Chen acknowledge the support of an iMQRES scholarship from Macquarie University. This work is partially supported by Australian Research Council (ARC) through its Centre of Excellence scheme (CE140100003) to E.M.G.

Compliance with ethical standards

The author(s) declare that they have no competing interests.

Supplementary material

604_2017_2145_MOESM1_ESM.docx (351 kb)
ESM 1(DOCX 350 kb)

References

  1. 1.
    Dougherty TJ, Gomer CJ, Henderson BW, Jori G, Kessel D, Korbelik M, Moan J, Peng Q (1998) Photodynamic therapy. J Natl Cancer Inst 90(12):889–905CrossRefGoogle Scholar
  2. 2.
    Macdonald IJ, Dougherty TJ (2001) Basic principles of photodynamic therapy. J Porphyrins Phthalocyanines 5(02):105–129CrossRefGoogle Scholar
  3. 3.
    DeRosa MC, Crutchley RJ (2002) Photosensitized singlet oxygen and its applications. Coord Chem Rev 233:351–371CrossRefGoogle Scholar
  4. 4.
    Khaing Oo MK, Yang Y, Hu Y, Gomez M, Du H, Wang H (2012) Gold nanoparticle-enhanced and size- dependent generation of reactive oxygen species from protoporphyrin IX. ACS Nano 6(3):1939–1947CrossRefGoogle Scholar
  5. 5.
    Savarimuthu WP, Gananathan P, Rao AP, Manickam E, Singaravelu G (2015) Protoporphyrin IX-gold nanoparticle conjugates for targeted photodynamic therapy–an In-vitro study. J Nanosci Nanotechnol 15(8):5577–5584CrossRefGoogle Scholar
  6. 6.
    Lucky SS, Soo KC, Zhang Y (2015) Nanoparticles in photodynamic therapy. Chem Rev 115(4):1990–2042CrossRefGoogle Scholar
  7. 7.
    Lucky SS, Muhammad Idris N, Li Z, Huang K, Soo KC, Zhang Y (2015) Titania coated upconversion nanoparticles for near-infrared light triggered photodynamic therapy. ACS Nano 9(1):191–205CrossRefGoogle Scholar
  8. 8.
    Jacques SL (2013) Optical properties of biological tissues: a review. Phys Med Biol 58(11):R37CrossRefGoogle Scholar
  9. 9.
    Yu J, Hsu C-H, Huang C-C, Chang P-Y (2014) Development of therapeutic Au–methylene blue nanoparticles for targeted photodynamic therapy of cervical cancer cells. ACS Appl Mater Interfaces 7(1):432–441CrossRefGoogle Scholar
  10. 10.
    Ferrari M (2005) Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer 5(3):161–171CrossRefGoogle Scholar
  11. 11.
    Clement S, Sobhan M, Deng W, Camilleri E, Goldys EM (2017) Nanoparticle-mediated singlet oxygen generation from photosensitizers. J Photochem Photobiol A Chem 332:66–71CrossRefGoogle Scholar
  12. 12.
    Maeda H, Wu J, Sawa T, Matsumura Y, Hori K (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65(1):271–284CrossRefGoogle Scholar
  13. 13.
     Li W-T (2009) Nanotechology-based strategies to enhance the efficacy of photodynamic therapy for cancers. Curr Drug Metab 10(8):851–860Google Scholar
  14. 14.
    da Silva CL, Ciampo D, Orestes J, Rossetti FC, Bentley MVLB, Pierre MBR (2013) PLGA nanoparticles as delivery systems for protoporphyrin IX in topical PDT: cutaneous penetration of photosensitizer observed by fluorescence microscopy. J Nanosci Nanotechnol 13(10):6533–6540CrossRefGoogle Scholar
  15. 15.
    Thienot E, Germain M, Piejos K, Simon V, Darmon A, Marill J, Borghi E, Levy L, Hochepied J-F, Pottier A (2010) One pot synthesis of new hybrid versatile nanocarrier exhibiting efficient stability in biological environment for use in photodynamic therapy. J Photochem Photobiol B Biol 100(1):1–9CrossRefGoogle Scholar
  16. 16.
    Hsu C-Y, Chen C-W, Yu H-P, Lin Y-F, Lai P-S (2013) Bioluminescence resonance energy transfer using luciferase-immobilized quantum dots for self-illuminated photodynamic therapy. Biomaterials 34(4):1204–1212CrossRefGoogle Scholar
  17. 17.
    Wang X, Liu K, Yang G, Cheng L, He L, Liu Y, Li Y, Guo L, Liu Z (2014) Near-infrared light triggered photodynamic therapy in combination with gene therapy using upconversion nanoparticles for effective cancer cell killing. Nanoscale 6(15):9198–9205CrossRefGoogle Scholar
  18. 18.
    Chen H, Wang GD, Chuang Y-J, Zhen Z, Chen X, Biddinger P, Hao Z, Liu F, Shen B, Pan Z (2015) Nanoscintillator-mediated X-ray inducible photodynamic therapy for in vivo cancer treatment. Nano Lett 15(4):2249–2256CrossRefGoogle Scholar
  19. 19.
    Clement S, Deng W, Camilleri E, Wilson BC, Goldys EM (2016) X-ray induced singlet oxygen generation by nanoparticle-photosensitizer conjugates for photodynamic therapy: determination of singlet oxygen quantum yield. Sci Rep 6. doi:10.1038/srep19954
  20. 20.
    El-Sayed IH, Huang X, El-Sayed MA (2006) Selective laser photo-thermal therapy of epithelial carcinoma using anti-EGFR antibody conjugated gold nanoparticles. Cancer Lett 239(1):129–135CrossRefGoogle Scholar
  21. 21.
    C-k K, Ghosh P, Rotello VM (2009) Multimodal drug delivery using gold nanoparticles. Nanoscale 1(1):61–67CrossRefGoogle Scholar
  22. 22.
    Yeh Y-C, Creran B, Rotello VM (2012) Gold nanoparticles: preparation, properties, and applications in bionanotechnology. Nanoscale 4(6):1871–1880CrossRefGoogle Scholar
  23. 23.
    Ashjari M, Dehfuly S, Fatehi D, Shabani R, Koruji M (2015) Efficient functionalization of gold nanoparticles using cysteine conjugated protoporphyrin IX for singlet oxygen production in vitro. RSC Adv 5(127):104621–104628CrossRefGoogle Scholar
  24. 24.
    Liu-Chittenden Y, Huang B, Shim JS, Chen Q, Lee S-J, Anders RA, Liu JO, Pan D (2012) Genetic and pharmacological disruption of the TEAD–YAP complex suppresses the oncogenic activity of YAP. Genes Dev 26(12):1300–1305CrossRefGoogle Scholar
  25. 25.
    Manson J, Kumar D, Meenan BJ, Dixon D (2011) Polyethylene glycol functionalized gold nanoparticles: the influence of capping density on stability in various media. Gold Bull 44(2):99–105CrossRefGoogle Scholar
  26. 26.
    Kim S, Fujitsuka M, Majima T (2013) Photochemistry of singlet oxygen sensor green. J Phys Chem B 117(45):13985–13992CrossRefGoogle Scholar
  27. 27.
    Shen Y, Lin H, Huang Z, Xiao L, Chen D, Li B, Xie S (2010) Kinetic analysis of singlet oxygen generation in a living cell using Singlet Oxygen Sensor Green. Proc. SPIE 7845, Optics in Health Care and Biomedical Optics IV, 78451FGoogle Scholar
  28. 28.
    Storhoff JJ, Elghanian R, Mucic RC, Mirkin CA, Letsinger RL (1998) One-pot colorimetric differentiation of polynucleotides with single base imperfections using gold nanoparticle probes. J Am Chem Soc 120(9):1959–1964CrossRefGoogle Scholar
  29. 29.
    Shenoy D, Fu W, Li J, Crasto C, Jones G, DiMarzio C, Sridhar S, Amiji M (2006) Surface functionalization of gold nanoparticles using hetero-bifunctional poly (ethylene glycol) spacer for intracellular tracking and delivery. Int J Nanomedicine 1(1):51CrossRefGoogle Scholar
  30. 30.
    Gao J, Huang X, Liu H, Zan F, Ren J (2012) Colloidal stability of gold nanoparticles modified with thiol compounds: bioconjugation and application in cancer cell imaging. Langmuir 28(9):4464–4471CrossRefGoogle Scholar
  31. 31.
    Lee SH, Bae KH, Kim SH, Lee KR, Park TG (2008) Amine-functionalized gold nanoparticles as non-cytotoxic and efficient intracellular siRNA delivery carriers. Int J Pharm 364(1):94–101CrossRefGoogle Scholar
  32. 32.
    Zhang Y, Aslan K, Malyn SN, Geddes CD (2006) Metal-enhanced phosphorescence (MEP). Chem Phys Lett 427(4):432–437CrossRefGoogle Scholar
  33. 33.
    Zhang Y, Aslan K, Previte MJ, Malyn SN, Geddes CD (2006) Metal-enhanced phosphorescence: interpretation in terms of triplet-coupled radiating plasmons. J Phys Chem B 110(49):25108–25114CrossRefGoogle Scholar
  34. 34.
    Mesbahi A (2010) A review on gold nanoparticles radiosensitization effect in radiation therapy of cancer. Rep Pract Oncol Radiother 15(6):176–180CrossRefGoogle Scholar
  35. 35.
    Jeremic B, Aguerri AR, Filipovic N (2013) Radiosensitization by gold nanoparticles. Clin Transl Oncol 15(8):593–601CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2017

Authors and Affiliations

  • Sandhya Clement
    • 1
  • Wenjie Chen
    • 1
  • Ayad G. Anwer
    • 1
  • Ewa M. Goldys
    • 1
  1. 1.ARC Centre for Nanoscale BioPhotonics (CNBP)Macquarie UniversitySydneyAustralia

Personalised recommendations