Skip to main content
SpringerLink
Log in

Visual dual chemodynamic/photothermal therapeutic nanoplatform based on superoxide dismutase plus Prussian blue

Nano Research Aims and scope Submit manuscript

Abstract

Enzyme-based anticancer therapy is more attractive for the less side effect than conventional chemotherapy. However, the poor stability and low membrane permeability of enzymes during the intracellular delivery are constraints for its practical applications. In this work, we synthesized novel near-infrared (NIR)-responsive core–shell-structured Prussian blue@fibrous SiO2 (PBFS) nanoparticles as the carrier of superoxide dismutase (SOD) and a glutathione (GSH)-activated Fenton reagent (DiFe). The PBFS nanoparticles are further modified with a GSH-responsive cationic polymer (poly(2-(acryloyloxy)-N,N-dimethyl-N-(4-(((2-((2-(((4-methyl-2-oxo-2H-chromen-7-yl)carbamoyl)oxy)ethyl)disulfaneyl) ethoxy)carbonyl)amino)benzyl)ethan-1-aminium, PSS) containing disulfide bonds and fluorophores. After SOD and DiFe are loaded on the PBFS-PSS nanoparticles, dual chemodynamic/photothermal therapeutic nanoparticulate systems (PBFS-PSS/DiFe/SOD) are obtained. In vitro experiments show that PBFS-PSS/DiFe/SOD nanoparticles have good biocompatibility and can be tracked under fluorescence microscope during the intracellular delivery process in MCF-7 tumor cells due to the GSH-activated release of fluorophores. They also exhibit high efficiency in NIR photothermal conversion and GSH-activated Fenton reaction in tumor cells, thus achieving high-efficient killing effect of tumor cells based on the combination of photothermal and chemodynamic therapeutic performance (PTT and CDT). This work offers a novel pathway to construct a visual multifunctional nanomedicine platform for future cancer therapy.

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

Access this article

Log in via an institution

Price includes VAT (France)

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Yan, M.; Du, J. J.; Gu, Z.; Liang, M.; Hu, Y. F.; Zhang, W. J.; Priceman, S.; Wu, L.; Zhou, Z. H.; Liu, Z. et al. A novel intracellular protein delivery platform based on single-protein nanocapsules. Nat. Nanotech. 2010, 5, 48–53.

    Article  Google Scholar 

  2. Trachootham, D.; Alexandre, J.; Huang, P. Targeting cancer cells by ROS-mediated mechanisms: A radical therapeutic approach? Nat. Rev. Drug Discov. 2009, 8, 579–591.

    Article  Google Scholar 

  3. Nelson, S. K.; Bose, S. K.; Grunwald, G. K.; Myhill, P.; McCord, J. M. The induction of human superoxide dismutase and catalase in vivo: A fundamentally new approach to antioxidant therapy. Free Radical Biol. Med. 2006, 40, 341–347.

    Article  Google Scholar 

  4. Tsang, C. K.; Liu, Y.; Thomas, J.; Zhang, Y. J.; Zheng, X. F. S. Superoxide dismutase 1 acts as a nuclear transcription factor to regulate oxidative stress resistance. Nat. Commun. 2014, 5, 3446.

    Article  Google Scholar 

  5. Cerutti, P. A. Prooxidant states and tumor promotion. Science 1985, 227, 375–381.

    Article  Google Scholar 

  6. Ma, P. A.; Xiao, H. H.; Yu, C.; Liu, J. H.; Cheng, Z. Y.; Song, H. Q.; Zhang, X. Y.; Li, C. X.; Wang, J. Q.; Gu, Z. et al. Enhanced cisplatin chemotherapy by iron oxide nanocarrier-mediated generation of highly toxic reactive oxygen species. Nano Lett. 2017, 17, 928–937.

    Article  Google Scholar 

  7. Dai, Y. L.; Yang, Z.; Cheng, S. Y.; Wang, Z. L.; Zhang, R. L.; Zhu, G. Z.; Wang, Z. T.; Yung, B. C.; Tian, R.; Jacobson, O. et al. Toxic reactive oxygen species enhanced synergistic combination therapy by self-assembled metal-phenolic network nanoparticles. Adv. Mater. 2018, 30, 1704877.

    Article  Google Scholar 

  8. Yang, Z.; Dai, Y. L.; Yin, C.; Fan, Q. L.; Zhang, W. S.; Song, J.; Yu, G. C.; Tang, W.; Fan, W. P.; Yung, B. C. et al. Activatable semiconducting theranostics: Simultaneous generation and ratiometric photoacoustic imaging of reactive oxygen species in vivo. Adv. Mater. 2018, 30, 1707509.

    Article  Google Scholar 

  9. Imlay, J.; Chin, S. M.; Linn, S. Toxic DNA damage by hydrogen peroxide through the Fenton reaction in vivo and in vitro. Science 1988, 240, 640–642.

    Article  Google Scholar 

  10. Kwon, B.; Han, E.; Yang, W.; Cho, W.; Yoo, W.; Hwang, J.; Kwon, B. M.; Lee, D. Nano-fenton reactors as a new class of oxidative stress amplifying anticancer therapeutic agents. ACS Appl. Mater. Interfaces 2016, 8, 5887–5897.

    Article  Google Scholar 

  11. Zhang, C.; Bu, W. B.; Ni, D. L.; Zhang, S. J.; Li, Q.; Yao, Z. W.; Zhang, J. W.; Yao, H. L.; Wang, Z.; Shi, J. L. Synthesis of iron nanometallic glasses and their application in cancer therapy by a localized Fenton reaction. Angew. Chem., Int. Ed. 2016, 55, 2101–2106.

    Article  Google Scholar 

  12. Kartha, S.; Yan, L. S.; Weisshaar, C. L.; Ita, M. E.; Shuvaev, V. V.; Muzykantov, V. R.; Tsourkas, A.; Winkelstein, B. A.; Cheng, Z. L. Superoxide dismutase-loaded porous polymersomes as highly efficient antioxidants for treating neuropathic pain. Adv. Healthcare Mater. 2017, 6, 1700500.

    Article  Google Scholar 

  13. Chen, Y. P.; Chen, C. T.; Hung, Y.; Chou, C. M.; Liu, T. P.; Liang, M. R.; Chen, C. T.; Mou, C. Y. A new strategy for intracellular delivery of enzyme using mesoporous silica nanoparticles: Superoxide dismutase. J. Am. Chem. Soc. 2013, 135, 1516–1523.

    Article  Google Scholar 

  14. Wang, X.; Niu, D. C.; Li, P.; Wu, Q.; Bo, X. W.; Liu, B. J.; Bao, S.; Su, T.; Xu, H. X.; Wang, Q. G. Dual-enzyme-loaded multifunctional hybrid nanogel system for pathological responsive ultrasound imaging and T2-weighted magnetic resonance imaging. ACS Nano 2015, 9, 5646–5656.

    Article  Google Scholar 

  15. Liu, W. L.; Liu, T.; Zou, M. Z.; Yu, W. Y.; Li, C. X.; He, Z. Y.; Zhang, M. K.; Liu, M. D.; Li, Z. H.; Feng, J. et al. Aggressive man-made red blood cells for hypoxia-resistant photodynamic therapy. Adv. Mater. 2018, 30, 1802006.

    Article  Google Scholar 

  16. Nukolova, N. V.; Aleksashkin, A. D.; Abakumova, T. O.; Morozova, A. Y.; Gubskiy, I. L.; Kirzhanova, E. A.; Abakumov, M. A.; Chekhonin, V. P.; Klyachko, N. L.; Kabanov, A. V. Multilayer polyion complex nanoformulations of superoxide dismutase 1 for acute spinal cord injury. J. Control. Release 2018, 270, 226–236.

    Article  Google Scholar 

  17. Huang, L.; Ao, L. J.; Hu, D. H.; Wang, W.; Sheng, Z. H.; Su, W. Magnetoplasmonic nanocapsules for multimodal-imaging and magnetically guided combination cancer therapy. Chem. Mater. 2016, 28, 5896–5904.

    Article  Google Scholar 

  18. Li, Z. L.; Hu, Y.; Miao, Z.; Xu, H.; Li, C.; Zhao, Y.; Li, Z.; Chang, M.; Ma, Z.; Sun, Y. et al. Dual-stimuli responsive bismuth nanoraspberries for multimodal imaging and combined cancer therapy. Nano Lett. 2018, 18, 6778–6788.

    Article  Google Scholar 

  19. Wang, Y. Z.; Song, Y. J.; Zhu, G. X.; Zhang, D. C.; Liu, X. W. Highly biocompatible BSA-MnO2 nanoparticles as an efficient near-infrared photothermal agent for cancer therapy. Chin. Chem. Lett. 2018, 29, 1685–1688.

    Article  Google Scholar 

  20. Wang, Z. R.; He, Q.; Zhao, W. G.; Luo, J. W.; Gao, W. P. Tumor-homing, pH- and ultrasound-responsive polypeptide-doxorubicin nanoconjugates overcome doxorubicin resistance in cancer therapy. J. Control. Release 2017, 264, 66–75.

    Article  Google Scholar 

  21. Cho, H. Y.; Lee, T.; Yoon, J.; Han, Z. L.; Rabie, H.; Lee, K. B.; Su, W. W.; Choi, J. W. Magnetic oleosome as a functional lipophilic drug carrier for cancer therapy. ACS Appl. Mater. Interfaces 2018, 10, 9301–9309.

    Article  Google Scholar 

  22. Lai, J. P.; Shah, B. P.; Garfunkel, E.; Lee, K. B. Versatile fluorescence resonance energy transfer-based mesoporous silica nanoparticles for real-time monitoring of drug release. ACS Nano 2013, 7, 2741–2750.

    Article  Google Scholar 

  23. Xu, Z. G.; Liu, S. Y.; Kang, Y. J.; Wang, M. F. Glutathione- and pH-responsive nonporous silica prodrug nanoparticles for controlled release and cancer therapy. Nanoscale 2015, 7, 5859–5868.

    Article  Google Scholar 

  24. Xie, Y. Y.; Wang, J.; Wang, M. Z.; Ge, X. W. Fabrication of fibrous amidoxime-functionalized mesoporous silica microsphere and its selectively adsorption property for Pb2+ in aqueous solution. J. Hazard. Mater. 2015, 297, 66–73.

    Article  Google Scholar 

  25. Chen, J. X.; Lei, S.; Xie, Y. Y.; Wang, M. Z.; Yang, J.; Ge, X. W. Fabrication of high-performance magnetic lysozyme-imprinted microsphere and its NIR-responsive controlled release property. ACS Appl. Mater. Interfaces 2015, 7, 28606–28615.

    Article  Google Scholar 

  26. Chen, J. X; Lei, S.; Zeng, K.; Wang, M. Z.; Asif, A.; Ge, X. W. Catalase-imprinted Fe3O4/Fe@fibrous SiO2/polydopamine nanoparticles: An integrated nanoplatform of magnetic targeting, magnetic resonance imaging, and dual-mode cancer therapy. Nano Res. 2017, 10, 2351–2363.

    Article  Google Scholar 

  27. Marzenell, P.; Hagen, H.; Sellner, L.; Zenz, T.; Grinyte, R.; Pavlov, V.; Daum, S.; Mokhir, A. Aminoferrocene-based prodrugs and their effects on human normal and cancer cells as well as bacterial cells. J. Med. Chem. 2013, 56, 6935–6944.

    Article  Google Scholar 

  28. Hagen, H.; Marzenell, P.; Jentzsch, E.; Wenz, F.; Veldwijk, M. R.; Mokhir, A. Aminoferrocene-based prodrugs activated by reactive oxygen species. J. Med. Chem. 2012, 55, 924–934.

    Article  Google Scholar 

  29. Wu, Q.; He, Z. G.; Wang, X.; Zhang, Q.; Wei, Q. C.; Ma, S. Q.; Ma, C.; Li, J. Y.; Wang, Q. G. Cascade enzymes within self-assembled hybrid nanogel mimicked neutrophil lysosomes for singlet oxygen elevated cancer therapy. Nat. Commun 2019, 10, 240.

    Article  Google Scholar 

  30. Li, W. P.; Su, C. H.; Tsao, L. C.; Chang, C. T.; Hsu, Y. P.; Yeh, C. S. Controllable CO release following near-infrared light-induced cleavage of iron carbonyl derivatized prussian blue nanoparticles for CO-assisted synergistic treatment. ACS Nano 2016, 10, 11027–11036.

    Article  Google Scholar 

  31. Chen, W. S.; Zeng, K.; Liu, H.; Ouyang, J.; Wang, L. Q.; Liu, Y.; Wang, H.; Deng, L.; Liu, Y. N. Cell membrane camouflaged hollow Prussian blue nanoparticles for synergistic photothermal-/chemotherapy of cancer. Adv. Funct. Mater. 2017, 27, 1605795.

    Article  Google Scholar 

  32. Zhou, B.; Jiang, B. P.; Sun, W. Y.; Wei, F. M.; He, Y.; Liang, H.; Shen, X. C. Water-dispersible Prussian blue hyaluronic acid nanocubes with near-infrared photoinduced singlet oxygen production and photothermal activities for cancer theranostics. ACS Appl. Mater. Interfaces 2018, 10, 18036–18049.

    Article  Google Scholar 

  33. Sing, K. S. W. Reporting physisorption data for gas/solid systems with special reference to the determination of surface area and porosity (Recommendations 1984). Pure Appl. Chem. 1985, 57, 603–619.

    Article  Google Scholar 

  34. Brunauer, S.; Deming, L. S.; Deming, W. E.; Teller, E. On a theory of the van der Waals adsorption of gases. J. Am. Chem. Soc. 1940, 62, 1723–1732.

    Article  Google Scholar 

  35. Mandel, R.; Ryser, H. J. P.; Niaki, B.; Ghani, F.; Shen, W. C. Isolation of variants of Chinese hamster ovary cells with abnormally low levels of GSH: Decreased ability to cleave endocytosed disulfide bonds. J. Cell. Physiol. 1991, 149, 60–65.

    Article  Google Scholar 

  36. Gandra, N.; Wang, D. D.; Zhu, Y.; Mao, C. B. Virus-mimetic cytoplasmcleavable magnetic/silica nanoclusters for enhanced gene delivery to mesenchymal stem cells. Angew. Chem., Int. Ed. 2013, 52, 11278–11281.

    Article  Google Scholar 

  37. Staben, L. R.; Koenig, S. G.; Lehar, S. M.; Vandlen, R.; Zhang, D. L.; Chuh, J.; Yu, S. F.; Ng, C.; Guo, J.; Liu, Y. Z. et al. Targeted drug delivery through the traceless release of tertiary and heteroaryl amines from antibody-drug conjugates. Nat. Chem. 2016, 8, 1112–1119.

    Article  Google Scholar 

  38. Liu, X.; Xiang, J. J.; Zhu, D. C.; Jiang, L. M.; Zhou, Z. X.; Tang, J. B.; Liu, X. R.; Huang, Y. Z.; Shen, Y. Q. Fusogenic reactive oxygen species triggered charge-reversal vector for effective gene delivery. Adv. Mater. 2016, 28, 1743–1752.

    Article  Google Scholar 

  39. Truong, N. P.; Jia, Z. F.; Burges, M.; McMillan, N. A. J.; Monteiro, M. J. Self-catalyzed degradation of linear cationic poly(2-dimethylaminoethyl acrylate) in water. Biomacromolecules 2011, 12, 1876–1882.

    Article  Google Scholar 

  40. Truong, N. P.; Gu, W. Y.; Prasadam, I.; Jia, Z. F.; Crawford, R.; Xiao, Y.; Monteiro, M. J. An influenza virus-inspired polymer system for the timed release of siRNA. Nat. Commun. 2013, 4, 1902.

    Article  Google Scholar 

  41. Kaneti, Y. V.; Chen, C. Y.; Liu, M. S.; Wang, X. C.; Yang, J. L.; Taylor, R. A.; Jiang, X. C.; Yu, A. B. Carbon-coated gold nanorods: A facile route to biocompatible materials for photothermal applications. ACS Appl. Mater. Interfaces 2015, 7, 25658–25668.

    Article  Google Scholar 

  42. Zhang, R. L.; Zhao, J.; Han, G. M.; Liu, Z. J.; Liu, C.; Zhang, C.; Liu, B. H.; Jiang, C. L.; Liu, R. Y.; Zhao, T. T. et al. Real-time discrimination and versatile profiling of spontaneous reactive oxygen species in living organisms with a single fluorescent probe. J. Am. Chem. Soc. 2016, 138, 3769–3778.

    Article  Google Scholar 

  43. Wang, Q.; Tian, S. L.; Ning, P. Degradation mechanism of methylene blue in a heterogeneous Fenton-like reaction catalyzed by ferrocene. Ind. Eng. Chem. Res. 2014, 53, 643–649.

    Article  Google Scholar 

  44. Lin, F. X.; Zeng, K.; Yang, W. X.; Wang, M. Z.; Rong, J. L.; Xie, J.; Zhao, Y.; Ge, X. W. γ-Ray-radiation-scissioned chitosan as a gene carrier and its improved in vitro gene transfection performance. Chin. J. Chem. Phys. 2017, 30, 231–238.

    Article  Google Scholar 

  45. Lin, M. T.; Beal, M. F. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 2006, 443, 787–795.

    Article  Google Scholar 

  46. Wang, S. H.; Shang, L.; Li, L. L.; Yu, Y. J.; Chi, C. W.; Wang, K.; Zhang, J.; Shi, R.; Shen, H. Y.; Waterhouse, G. I. N. et al. Metal-organic-frameworkderived mesoporous carbon nanospheres containing porphyrin-like metal centers for conformal phototherapy. Adv. Mater. 2016, 28, 8379–8387.

    Article  Google Scholar 

  47. Qu, X. W.; Qiu, P. H.; Zhu, Y.; Yang, M. Y.; Mao, C. B. Guiding nanomaterials to tumors for breast cancer precision medicine: From tumor-targeting small-molecule discovery to targeted nanodrug delivery. NPG Asia Mater. 2017, 9, e452.

    Article  Google Scholar 

  48. Simón-Gracia, L.; Hunt, H.; Teesalu, T. Peritoneal carcinomatosis targeting with tumor homing peptides. Molecules 2018, 23, 1190.

    Article  Google Scholar 

  49. Hu, M.; Furukawa, S.; Ohtani, R.; Sukegawa, H.; Nemoto, Y.; Reboul, J.; Kitagawa, S.; Yamauchi, Y. Synthesis of Prussian blue nanoparticles with a hollow interior by controlled chemical etching. Angew. Chem., Int. Ed. 2012, 124, 1008–1012.

    Article  Google Scholar 

  50. Zhang, Y. Y.; Ang, C. Y.; Li, M. H.; Tan, S. Y.; Qu, Q. Y.; Zhao, Y. L. Polymeric prodrug grafted hollow mesoporous silica nanoparticles encapsulating near-infrared absorbing dye for potent combined photothermalchemotherapy. ACS Appl. Mater. Interfaces 2016, 8, 6869–6879.

    Article  Google Scholar 

  51. Wang, C.; Wang, J. Q.; Zhang, X. D.; Yu, S. J.; Wen, D.; Hu, Q. Y.; Ye, Y. Q.; Bomba, H.; Hu, X. L.; Liu, Z. et al. In situ formed reactive oxygen species-responsive scaffold with gemcitabine and checkpoint inhibitor for combination therapy. Sci. Transl. Med. 2018, 10, eaan3682.

    Article  Google Scholar 

  52. Li, Y. M.; Liu, G. H.; Wang, X. R.; Hu, J. M.; Liu, S. Y. Enzyme-responsive polymeric vesicles for bacterial-strain-selective delivery of antimicrobial agents. Angew. Chem., Int. Ed. 2016, 55, 1760–1764.

    Article  Google Scholar 

Download references

Acknowledgements

We thank Prof. Z. S. Ge and Prof. L. H. Yang in the Department of Polymer Science and Engineering of USTC for their kind help in providing the 808 nm semiconductor laser device and infrared imaging devices, respectively. This work was supported by the National Natural Science Foundation of China (Nos. 51473152 and 51573174).

Author information

Authors and Affiliations

  1. CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, 230026, China

    Shan Lei, Jinxing Chen, Kun Zeng, Mozhen Wang & Xuewu Ge

Authors
  1. Shan Lei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jinxing Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kun Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mozhen Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xuewu Ge
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Mozhen Wang or Xuewu Ge.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lei, S., Chen, J., Zeng, K. et al. Visual dual chemodynamic/photothermal therapeutic nanoplatform based on superoxide dismutase plus Prussian blue. Nano Res. 12, 1071–1082 (2019). https://doi.org/10.1007/s12274-019-2348-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12274-019-2348-1

Keywords

search

Navigation