Skip to main content
SpringerLink
Log in

Gold nanoparticle/ZnO nanorod hybrids for enhanced reactive oxygen species generation and photodynamic therapy

  • Research Article
  • Published:
Nano Research Aims and scope Submit manuscript

Abstract

Gold nanoparticle (Au NP)@ZnO nanorod (NR) (Au@ZnO) hybrids with various ZnO:Au molar ratios were developed to enhance the generation of reactive oxygen species (ROS) in photodynamic therapy (PDT) applications. Introducing a metal/semiconductor heterostructure interface between Au NPs and ZnO NRs modulated electron transfer under ultraviolet (UV) irradiation, which dramatically suppressed the electron-hole recombination in ZnO and simultaneously increased the amount of excited electrons with high energy at Au NP surfaces. Hence, the ROS yield of the nanohybrid was considerably improved over those of pristine Au NPs or ZnO NRs alone and demonstrated a “1 + 1 > 2 effect.” This enhancement was strengthened with increases in the proportion of Au in the hybrid. The results showed that the Au@ZnO nanohybrids with a ZnO:Au ratio of 20:1 generated the highest ROS yield because they had the largest interface area between Au and ZnO, which in turn led to the lowest cell viability for HeLa and C2C12 cells during PDT. Furthermore, both ROS generation and cell destruction were positively correlated with nanohybrid dosage. The Au@ZnO hybrid (20:1, 100 μg/mL) resulted in HeLa cell viability as low as 28% after UV exposure for 2 min, which indicated its promising potential to improve the therapeutic efficacy of PDT.

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

References

  1. Guo, H. C.; Qian, H. S.; Idris, N. M.; Zhang, Y. Singlet oxygen-induced apoptosis of cancer cells using upconversion fluorescent nanoparticles as a carrier of photosensitizer. Nanomedicine 2010, 6, 486–495.

    Article  Google Scholar 

  2. Bae, B. C.; Na, K. Self-quenching polysaccharide-based nanogels of pullulan/folate-photosensitizer conjugates for photodynamic therapy. Biomaterials 2010, 31, 6325–6335.

    Article  Google Scholar 

  3. Idris, N. M.; Gnanasammandhan, M. K.; Zhang, J.; Ho, P. C.; Mahendran, R.; Zhang, Y. In vivo photodynamic therapy using upconversion nanoparticles as remote-controlled nanotransducers. Nat. Med. 2012, 18, 1580–1585.

    Article  Google Scholar 

  4. Kato, H. Photodynamic therapy for lung cancer—a review of 19 years’ experience. J. Photochem. Photobiol. B 1998, 42, 96–99.

    Article  Google Scholar 

  5. Schuller, D. E.; McCaughan J. S.; Rock, R. P. Photodynamic therapy in head and neck cancer. Arch. Otolaryngol. 1985, 111, 351–355.

    Article  Google Scholar 

  6. Skyrme, R. J.; French, A. J.; Datta, S. N.; Allman, R.; Mason, M. D.; Matthews, P. N. A phase-1 study of sequential mitomycin C and 5-aminolaevulinic acid-mediated photodynamic therapy in recurrent superficial bladder carcinoma. BJU Int. 2005, 95, 1206–1210.

    Article  Google Scholar 

  7. Rhodes, L. E.; de Rie, M.; Enstrom, Y.; Groves, R.; Morken, T.; Goulden, V.; Wong, G. A.; Grob, J. J.; Varma, S.; Wolf, P. Photodynamic therapy using topical methyl aminolevulinate vs. surgery for nodular basal cell carcinoma: Results of a multi-center randomized prospective trial. Arch. Dermatol. 2004, 140, 17–23.

    Google Scholar 

  8. Henderson, B. W.; Dougherty, T. J. How does photodynamic therapy work? Photochem. Photobiol. 1992, 55, 145–157.

    Article  Google Scholar 

  9. He, X. X.; Wu, X.; Wang, K. M.; Shi, B. H.; Hai, L. Methylene blue-encapsulated phosphonate-terminated silica nanoparticles for simultaneous in vivo imaging and photodynamic therapy. Biomaterials 2009, 30, 5601–5609.

    Article  Google Scholar 

  10. Celli, J. P.; Spring, B. Q.; Rizvi, I.; Evans, C. L.; Samkoe, K. S.; Verma, S.; Pogue, B. W.; Hasan, T. Imaging and photodynamic therapy: Mechanisms, monitoring, and optimization. Chem. Rev. 2010, 110, 2795–2838.

    Article  Google Scholar 

  11. Dougherty, T. J.; Gomer, C. J.; Henderson, B. W.; Jori, G.; Kessel, D.; Korbelik, M.; Moan, J.; Peng, Q. Photodynamic therapy. J. Nat. Cancer Inst. 1998, 90, 889–905.

    Article  Google Scholar 

  12. Foote, C. S. Photosensitized oxygenations and the role of singlet oxygen. Acc. Chem. Res. 1968, 1, 104–110.

    Article  Google Scholar 

  13. Buttke, T. M.; Sandstrom, P. A. Oxidative stress as a mediator of apoptosis. Immunol. Today 1994, 15, 7–10.

    Article  Google Scholar 

  14. Brown, S. B.; Brown, E. A.; Walker, I. The present and future role of photodynamic therapy in cancer treatment. Lancet Oncol. 2004, 5, 497–508.

    Article  Google Scholar 

  15. Zhang, H. J.; Chen, B. A.; Jiang, H.; Wang, C. L.; Wang, H. P.; Wang, X. M. A strategy for ZnO nanorod mediated multi-mode cancer treatment. Biomaterials 2011, 32, 1906–1914.

    Article  Google Scholar 

  16. Guo, D. D.; Wu, C. H.; Jiang, H.; Li, Q. N.; Wang, X. M.; Chen, B. A. Synergistic cytotoxic effect of different sized ZnO nanoparticles and daunorubicin against leukemia cancer cells under UV irradiation. J. Photochem. Photobiol. B 2008, 93, 119–126.

    Article  Google Scholar 

  17. Ostrovsky, S.; Kazimirsky, G.; Gedanken, A.; Brodie, C. Selective cytotoxic effect of ZnO nanoparticles on glioma cells. Nano Res. 2009, 2, 882–890.

    Article  Google Scholar 

  18. Li, J. Y.; Guo, D. D.; Wang, X. M.; Wang, H. P.; Jiang, H.; Chen, B. A. The photodynamic effect of different size ZnO nanoparticles on cancer cell proliferation in vitro. Nanoscale Res. Lett. 2010, 5, 1063–1071.

    Article  Google Scholar 

  19. Zhang, Y. B.; Chen, W.; Wang, S. P.; Liu, Y. F.; Pope, C. Phototoxicity of zinc oxide nanoparticle conjugatesin human ovarian cancer NIH: OVCAR-3 cells. J. Biomed. Nanotechnol. 2008, 4, 432–438.

    Article  Google Scholar 

  20. Ahamed, M.; Akhtar, M. J.; Raja, M.; Ahmad, I.; Siddiqui, M. K. J.; AlSalhi, M. S.; Alrokayan, S. A. ZnO nanorod-induced apoptosis in human alveolar adenocarcinoma cells via P53, survivin and Bax/Bcl-2 pathways: Role of oxidative stress. Nanomedicine 2011, 7, 904–913.

    Article  Google Scholar 

  21. Dutta, R. K.; Nenavathu, B. P.; Gangishetty, M. K.; Reddy, A. V. R. Studies on antibacterial activity of ZnO nanoparticles by ROS induced lipid peroxidation. Colloids Surf. B 2012, 94, 143–150.

    Article  Google Scholar 

  22. Misawa, M.; Takahashi, J. Generation of reactive oxygen species induced by gold nanoparticles under X-ray and UV irradiations. Nanomedicine 2011, 7, 604–614.

    Article  Google Scholar 

  23. Khaing Oo, M. K.; Yang, Y. M.; Hu, Y.; Gomez, M.; Du, H.; Wang, H. J. Gold nanoparticle-enhanced and size-dependent generation of reactive oxygen species from protoporphyrin IX. ACS Nano 2012, 6, 1939–1947.

    Article  Google Scholar 

  24. Minai, L.; Yeheskely-Hayon, D.; Yelin, D. High levels of reactive oxygen species in gold nanoparticle-targeted cancer cells following femtosecond pulse irradiation. Sci. Rep. 2013, 3. 2146.

    Article  Google Scholar 

  25. Wang, S. T.; Chen, K. J.; Wu, T. H.; Wang, H.; Lin, W. Y.; Ohashi, M.; Chiou, P. Y.; Tseng, H. R. Photothermal effects of supramolecularly assembled gold nanoparticles for the targeted treatment of cancer cells. Angew. Chem. Int. Edit. 2010, 49, 3777–3781.

    Article  Google Scholar 

  26. Zhao, Y. Y.; Jiang, X. Y. Multiple strategies to activate gold nanoparticles as antibiotics. Nanoscale 2013, 5, 8340–8350.

    Article  Google Scholar 

  27. Khaing Oo, M. K.; Yang, X. C.; Du, H.; Wang, H. J. 5-Aminolevulinic acid-conjugated gold nanoparticles for photodynamic therapy of cancer. Nanomedicine 2008, 3, 777–786.

    Article  Google Scholar 

  28. Wang, J.; Zhu, G. Z.; You, M. X.; Song, E. Q.; Shukoor, M. I.; Zhang, K. J.; Altman, M. B.; Chen, Y.; Zhu, Z.; Huang, C. Z. et al. Assembly of aptamer switch probes and photosensitizer on gold nanorods for targeted photothermal and photodynamic cancer therapy. ACS Nano 2012, 6, 5070–5077.

    Article  Google Scholar 

  29. Tong, L.; Zhao, Y.; Huff, T. B.; Hansen, M. N.; Wei, A.; Cheng, J. X. Gold nanorods mediate tumor cell death by compromising membrane integrity. Adv. Mater. 2007, 19, 3136–3141.

    Article  Google Scholar 

  30. Li, J. L.; Day, D.; Gu, M. Ultra-low energy threshold for cancer photothermal therapy using transferrin-conjugated gold nanorods. Adv. Mater. 2008, 20, 3866–3871.

    Article  Google Scholar 

  31. Jang, B.; Park, J. Y.; Tung, C. H.; Kim, I. H.; Choi, Y. Gold nanorod-photosensitizer complex for near-infrared fluorescence imaging and photodynamic/photothermal therapy in vivo. ACS Nano 2011, 5, 1086–1094.

    Article  Google Scholar 

  32. Choi, W. I.; Kim, J. Y.; Kang, C.; Byeon, C. C.; Kim, Y. H.; Tae, G. Tumor regression in vivo by photothermal therapy based on gold-nanorod-loaded, functional nanocarriers. ACS Nano 2011, 5, 1995–2003.

    Article  Google Scholar 

  33. Wang, N. N.; Zhao, Z. L.; Lv, Y. F.; Fan, H. H.; Bai, H. R.; Meng, H. M.; Long, Y. Q.; Fu, T.; Zhang, X. B.; Tan, W. H. Gold nanorod-photosensitizer conjugate with extracellular pH-driven tumor targeting ability for photothermal/photodynamic therapy. Nano Res. 2014, 7, 1291–1301.

    Article  Google Scholar 

  34. Terentyuk, G.; Panfilova, E.; Khanadeev, V.; Chumakov, D.; Genina, E.; Bashkatov, A.; Tuchin, V.; Bucharskaya, A.; Maslyakova, G.; Khlebtsov, N. et al. Gold nanorods with a hematoporphyrin-loaded silica shell for dual-modality photodynamic and photothermal treatment of tumors in vivo. Nano Res. 2014, 7, 325–337.

    Article  Google Scholar 

  35. Gao, L.; Fei, J. B.; Zhao, J.; Li, H.; Cui, Y.; Li, J. B. Hypocrellin-loaded gold nanocages with high two-photon efficiency for photothermal/photodynamic cancer therapy in vitro. ACS Nano 2012, 6, 8030–8040.

    Article  Google Scholar 

  36. Xia, Y. N.; Li, W. Y.; Cobley, C. M.; Chen, J. Y.; Xia, X. H.; Zhang, Q.; Yang, M. X.; Cho, E. C.; Brown, P. K. Gold nanocages: From synthesis to theranostic applications. Acc. Chem. Res. 2011, 44, 914–924.

    Article  Google Scholar 

  37. Liu, H. Y.; Chen, D.; Tang, F. Q.; Du, G. J.; Li, L. L.; Meng, X. W.; Liang, W.; Zhang, Y. D.; Teng, X.; Li, Y. Photothermal therapy of lewis lung carcinoma in mice using gold nanoshells on carboxylated polystyrene spheres. Nanotechnology 2008, 19, 455101.

    Article  Google Scholar 

  38. Li, C. M.; Chen, T.; Ocsoy, I.; Zhu, G. Z.; Yasun, E.; You, M. X.; Wu, C. C.; Zheng, J.; Song, E.; Huang, C. Z.; Tan, W. H. Gold-coated Fe3O4 nanoroses with five unique functions for cancer cell targeting, imaging, and therapy. Adv. Func. Mater. 2014, 24, 1772–1780.

    Article  Google Scholar 

  39. He, W. W.; Kim, H. K.; Wamer, W. G.; Melka, D.; Callahan, J. H.; Yin, J. J. Photogenerated charge carriers and reactive oxygen species in ZnO/Au hybrid nanostructures with enhanced photocatalytic and antibacterial activity. J. Am. Chem. Soc. 2013, 136, 750–757.

    Article  Google Scholar 

  40. Chatterjee, D. K.; Fong, L. S.; Zhang, Y. Nanoparticles in photodynamic therapy: An emerging paradigm. Adv. Drug Deliv. Rev. 2008, 60, 1627–1637.

    Article  Google Scholar 

  41. Paszko, E.; Ehrhardt, C.; Senge, M. O.; Kelleher, D. P.; Reynolds, J. V. Nanodrug applications in photodynamic therapy. Photodiagn. Photodyn. 2011, 8, 14–29.

    Article  Google Scholar 

  42. Shan, J. N.; Budijono, S. J.; Hu, G. H.; Yao, N.; Kang, Y. B.; Ju, Y. G.; Prud’homme, R. K. Pegylated composite nanoparticles containing upconverting phosphors and meso-tetraphenyl porphine (TPP) for photodynamic therapy. Adv. Func. Mater. 2011, 21, 2488–2495.

    Article  Google Scholar 

  43. Diebold, U.; Koplitz, L. V.; Dulub, O. Atomic-scale properties of low-index ZnO surfaces. Appl. Surf. Sci. 2004, 237, 336–342.

    Article  Google Scholar 

  44. Zhang, W. Q.; Lu, Y.; Zhang, T. K.; Xu, W. P.; Zhang, M.; Yu, S. H. Controlled synthesis and biocompatibility of water-soluble ZnO nanorods/Au nanocomposites with tunable UV and visible emission intensity. J. Phys. Chem. C 2008, 112, 19872–19877.

    Article  Google Scholar 

  45. Fu, Q.; Saltsburg, H.; Flytzani-Stephanopoulos, M. Active nonmetallic Au and Pt species on ceria-based water-gas shift catalysts. Science 2003, 301, 935–938.

    Article  Google Scholar 

  46. Soh, N. Recent advances in fluorescent probes for the detection of reactive oxygen species. Anal. Bioanal. Chem. 2006, 386, 532–543.

    Article  Google Scholar 

  47. Crow, J. P. Dichlorodihydrofluorescein and dihydrorhodamine 123 are sensitive indicators of peroxynitrite in vitro: Implications for intracellular measurement of reactive nitrogen and oxygen species. Nitric Oxide 1997, 1, 145–157.

    Article  Google Scholar 

  48. Bai, X. D.; Wang, E. G.; Gao, P. X.; Wang, Z. L. Measuring the work function at a nanobelt tip and at a nanoparticle surface. Nano Lett. 2003, 3, 1147–1150.

    Article  Google Scholar 

  49. Wang, X. D.; Summers, C. J.; Wang, Z. L. Self-attraction among aligned Au/ZnO nanorods under electron beam. Appl. Phys. Lett. 2005, 86, 013111.

    Article  Google Scholar 

  50. Wang, X.; Kong, X. G.; Yu, Y.; Zhang, H. Synthesis and characterization of water-soluble and bifunctional ZnO-Au nanocomposites. J. Phys. Chem. C 2007, 111, 3836–3841.

    Article  Google Scholar 

  51. Cui, S. S.; Yin, D. Y.; Chen, Y. Q.; Di, Y. F.; Chen, H. Y.; Ma, Y. X.; Achilefu, S.; Gu, Y. Q. In vivo targeted deep-tissue photodynamic therapy based on near-infrared light triggered upconversion nanoconstruct. ACS Nano 2012, 7, 676–688.

    Article  Google Scholar 

  52. Zhao, F.; Zhao, Y.; Liu, Y.; Chang, X. L.; Chen, C. Y.; Zhao, Y. L. Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials. Small 2011, 7, 1322–1337.

    Article  Google Scholar 

  53. Chithrani, B. D.; Ghazani, A. A.; Chan, W. C. Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett. 2006, 6, 662–668.

    Article  Google Scholar 

  54. Zhang, Y.; Yan, X. Q.; Yang, Y.; Huang, Y. H.; Liao, Q. L. Scanning probe study on the piezoelectric effect in ZnO nanomaterials and nanodevices. Adv. Mater. 2012, 24, 4647–4655.

    Article  Google Scholar 

  55. Zhao, Y. G.; Fang, X. F.; Gu, Y. S.; Yan, X. Q.; Kang, Z.; Zheng, X.; Lin, P.; Zhao, L. C.; Zhang, Y. Gold nanoparticles coated zinc oxide nanorods as the matrix for enhanced l-lactate sensing. Colloids Surf. B 2015, 126, 476–480.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. State Key Laboratory for Advanced Metals and Materials, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing, 100083, China

    Zhuo Kang, Xiaoqin Yan, Qingliang Liao, Kun Zhao, Xiaohui Zhang & Yue Zhang

  2. Department of Biotechnology, School of Chemistry and Biology Engineering, University of Science and Technology Beijing, Beijing, 100083, China

    Lanqing Zhao & Hongwu Du

  3. Research Center for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 100083, China

    Xueji Zhang

  4. Key Laboratory of New Energy Materials and Technologies, University of Science and Technology Beijing, Beijing, 100083, China

    Yue Zhang

Authors
  1. Zhuo Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaoqin Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lanqing Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qingliang Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kun Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hongwu Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiaohui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xueji Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yue Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yue Zhang.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kang, Z., Yan, X., Zhao, L. et al. Gold nanoparticle/ZnO nanorod hybrids for enhanced reactive oxygen species generation and photodynamic therapy. Nano Res. 8, 2004–2014 (2015). https://doi.org/10.1007/s12274-015-0712-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12274-015-0712-3

Keywords

Search

Navigation