Skip to main content
SpringerLink
Log in

ZIF-8 coated gold nanospheres: a multi-responsive drug delivery system promoting the killing effect of photothermal therapy against osteosarcoma cells

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

Abstract

Photothermal therapy (PTT) has been widely used in the treatment of tumors, but its efficacy is greatly limited by the inability of precise drug delivery and the increase of heat shock proteins (HSPs) caused by high temperature. This article describes a therapeutic strategy to enhance PTT with starvation therapy in conjunction with ferroptosis mechanism. A nanoparticle platform ZIF-8@GA was constructed by wrapping together glucose oxidase (GOX) and gold nanospheres (AuNPs) loaded with dihydroartemisinin (DHA) with zeolitic imidazolate framework-8 (ZIF-8). This platform can take advantage of the micro-environment of osteosarcoma (OS) cells, featuring low pH and high reactive oxygen species (ROS), for precision drug delivery. GOX can effectively catalyze glucose to produce gluconic acid and H2O2, and DHA can also induce ROS production in OS cells. ROS produced by GOX and DHA can further generate lipid peroxidation (LPO) and lead to ferroptosis of OS cells. At the same time, ROS and LPO produced can inhibit the expression of HSPs, thereby increasing the therapeutic effect of PTT. In vitro experiments show that the nanoparticles are pH and ROS responsive. 1 µg/mL GOX combined with 0.2 µg/mL DHA promotes ferroptosis of OS cells, and increases the killing effect of near-infrared (NIR) on OS cells. Further in vivo experiments showed that the nano drug-delivery platform combined with PTT can effectively inhibit the growth of OS cells. Meanwhile, this study provides a new idea for the treatment of OS with biomaterials combined with various treatment methods.

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. Ritter, J.; Bielack, S. S. Osteosarcoma. Ann. Oncol. 2010, 21, VII320–VII325.

    Article  PubMed  Google Scholar 

  2. Stiller, C. A.; Craft, A. W.; Corazziari, I.; The EUROCARE Working Group. Survival of children with bone sarcoma in Europe since 1978: Results from the EUROCARE study. Eur. J. Cancer 2001, 37, 760–766.

    Article  CAS  PubMed  Google Scholar 

  3. Bielack, S. S.; Kempf-Bielack, B.; Delling, G.; Exner, G. U.; Flege, S.; Helmke, K.; Kotz, R.; Salzer-Kuntschik, M.; Werner, M.; Winkelmann, W. et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: An analysis of 1, 702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J. Clin. Oncol. 2002, 20, 776–790.

    Article  PubMed  Google Scholar 

  4. Kager, L.; Zoubek, A.; Potschger, U.; Kastner, U.; Flege, S.; Kempf-Bielack, B.; Branscheid, D.; Kotz, R.; Salzer-Kuntschik, M.; Winkelmann, W. et al. Primary metastatic osteosarcoma: Presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J. Clin. Oncol. 2003, 21, 2011–2018.

    Article  PubMed  Google Scholar 

  5. Kim, H.; Chung, K.; Lee, S.; Kim, D. H.; Lee, H. Near-infrared light-responsive nanomaterials for cancer theranostics. WIREs Nanomed. Nanobiotechnol. 2016, 8, 23–45.

    Article  CAS  Google Scholar 

  6. Huang, X. Q.; Tang, S. H.; Mu, X. L.; Dai, Y.; Chen, G. X.; Zhou, Z. Y.; Ruan, F. X.; Yang, Z. L.; Zheng, N. F. Freestanding palladium nanosheets with plasmonic and catalytic properties. Nat. Nanotechnol. 2011, 6, 28–32.

    Article  ADS  CAS  PubMed  Google Scholar 

  7. Tian, Q. W.; Hu, J. Q.; Zhu, Y. H.; Zou, R. J.; Chen, Z. G.; Yang, S. P.; Li, R. W.; Su, Q. Q.; Han, Y.; Liu, X. G. Sub-10 nm Fe3O4@Cu2-xS core-shell nanoparticles for dual-modal imaging and photothermal therapy. J. Am. Chem. Soc. 2013, 135, 8571–8577.

    Article  CAS  PubMed  Google Scholar 

  8. Hu, K.; Xie, L.; Zhang, Y. D.; Hanyu, M.; Yang, Z. M.; Nagatsu, K.; Suzuki, H.; Ouyang, J.; Ji, X. Y.; Wei, J. J. et al. Marriage of black phosphorus and Cu2+ as effective photothermal agents for PET-guided combination cancer therapy. Nat. Commun. 2020, 11, 2778.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  9. Jiang, Z. Q.; Yuan, B.; Wang, Y. J.; Wei, Z. N.; Sun, S.; Akakuru, O. U.; Li, Y.; Li, J.; Wu, A. G. Near-infrared heptamethine cyanine dye-based nanoscale coordination polymers with intrinsic nucleus-targeting for low temperature photothermal therapy. Nano Today 2020, 34, 100910.

    Article  CAS  Google Scholar 

  10. Ying, W. W.; Zhang, Y.; Gao, W.; Cai, X. J.; Wang, G.; Wu, X. F.; Chen, L.; Meng, Z. Y.; Zheng, Y. Y.; Hu, B. et al. Hollow magnetic nanocatalysts drive starvation-chemodynamic-hyperthermia synergistic therapy for tumor. ACS Nano 2020, 14, 9662–9674.

    Article  CAS  PubMed  Google Scholar 

  11. Raza, M.; Chakraborty, S.; Choudhury, M.; Ghosh, P. C.; Nag, A. Cellular iron homeostasis and therapeutic implications of iron chelators in cancer. Curr. Pharm. Biotechnol. 2014, 15, 1125–1140.

    Article  CAS  PubMed  Google Scholar 

  12. Andrews, N. C. Iron homeostasis: Insights from genetics and animal models. Nat. Rev. Genet. 2000, 1, 208–217.

    Article  CAS  PubMed  Google Scholar 

  13. Basuli, D.; Tesfay, L.; Deng, Z.; Paul, B.; Yamamoto, Y.; Ning, G.; Xian, W.; Mckeon, F.; Lynch, M.; Crum, C. P. et al. Iron addiction: A novel therapeutic target in ovarian cancer. Oncogene 2017, 36, 4089–4099.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Dixon, S. J.; Lemberg, K. M.; Lamprecht, M. R.; Skouta, R.; Zaitsev, E. M.; Gleason, C. E.; Patel, D. N.; Bauer, A. J.; Cantley, A. M.; Yang, W. S. et al. Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell 2012, 149, 1060–1072.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Yang, W. S.; Stockwell, B. R. Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem. Biol. 2008, 15, 234–245.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Friedmann Angeli, J. P.; Schneider, M.; Proneth, B.; Tyurina, Y. Y.; Tyurin, V. A.; Hammond, V. J.; Herbach, N.; Aichler, M.; Walch, A.; Eggenhofer, E. et al. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat. Cell Biol. 2014, 16, 1180–1191.

    Article  CAS  PubMed  Google Scholar 

  17. He, Q.; Shi, J. X.; Shen, X. L.; An, J.; Sun, H.; Wang, L.; Hu, Y. J.; Sun, Q.; Fu, L. C.; Sheikh, M. S. et al. Dihydroartemisinin upregulates death receptor 5 expression and cooperates with TRAIL to induce apoptosis in human prostate cancer cells. Cancer Biol. Ther. 2010, 9, 819–824.

    Article  CAS  PubMed  Google Scholar 

  18. Fasano, E.; Serini, S.; Piccioni, E.; Toesca, A.; Monego, G.; Cittadini, A. R.; Ranelletti, F. O.; Calviello, G. DHA induces apoptosis by altering the expression and cellular location of GRP78 in colon cancer cell lines. Biochim. Biophys. Acta (BBA)-Mol. Basis Dis. 2012, 1822, 1762–1772.

    Article  CAS  Google Scholar 

  19. Han, N.; Li, L. G.; Peng, X. C.; Ma, Q. L.; Yang, Z. Y.; Wang, X. Y.; Li, J.; Li, Q. R.; Yu, T. T.; Xu, H. Z. et al. Ferroptosis triggered by dihydroartemisinin facilitates chlorin e6 induced photodynamic therapy against lung cancerthrough inhibiting GPX4 and enhancing ROS. Eur. J. Pharmacol. 2022, 919, 174797.

    Article  CAS  PubMed  Google Scholar 

  20. Bankar, S. B.; Bule, M. V.; Singhal, R. S.; Ananthanarayan, L. Glucose oxidase-An overview. Biotechnol. Adv. 2009, 27, 489–501.

    Article  CAS  PubMed  Google Scholar 

  21. Dinda, S.; Sarkar, S.; Das, P. K. Glucose oxidase mediated targeted cancer-starving therapy by biotinylated self-assembled vesicles. Chem. Commun. 2018, 54, 9929–9932.

    Article  CAS  Google Scholar 

  22. Wang, C.; Ye, Y. Q.; Hochu, G. M.; Sadeghifar, H.; Gu, Z. Enhanced cancer immunotherapy by microneedle patch-assisted delivery of anti-PDl antibody. Nano Lett. 2016, 16, 2334–2340.

    Article  ADS  CAS  PubMed  Google Scholar 

  23. Li, Z. F.; Li, M.; Tan, B.; Du, N.; Zhang, Q.; Li, C. W.; Zhang, Y. B.; Li, J. W.; Li, J. Y. Green rust (GR) and glucose oxidase (GOX) based Fenton-like reaction: Capacity of sustainable release, promoted conversion of glucose through GOX-iron and pH self-adjustment. Environ. Res. 2022, 208, 112656–112666.

    Article  CAS  PubMed  Google Scholar 

  24. Okkeh, M.; Bloise, N.; Restivo, E.; De Vita, L.; Pallavicini, P.; Visai, L. Gold nanoparticles: Can they Be the next magic bullet for multidrug-resistant bacteria. Nanomaterials 2021, 11, 312.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Singh, P.; Pandit, S.; Mokkapati, V.; Mokkapati, V. R. S. S.; Garg, A.; Ravikumar, V.; Mijakovic, I. Gold nanoparticles in diagnostics and therapeutics for human cancer. Int. J. Mol. Sci. 2018, 19, 1979.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Comenge, J.; Puntes, V. F. Stabilizing gold nanoparticle bioconjugates in physiological conditions by PEGylation.. In Methods in Molecular Biology 2013, 1025, 281–289.

    Article  CAS  Google Scholar 

  27. Sava Gallis, D. F.; Butler, K. S.; Agola, J. O.; Pearce, C. J.; Mcbride, A. A. Antibacterial countermeasures via metal-organic framework-supported sustained therapeutic release. ACS Appl. Mater. Interfaces 2019, 11, 7782–7791.

    Article  CAS  PubMed  Google Scholar 

  28. Peng, S. J.; Liu, J. S.; Qin, Y.; Wang, H.; Cao, B. L.; Lu, L. G.; Yu, X. R. Metal-organic framework encapsulating hemoglobin as a high-stable and long-circulating oxygen carriers to treat hemorrhagic shock. ACS Appl. Mater. Interfaces 2019, 11, 35604–35612.

    Article  CAS  PubMed  Google Scholar 

  29. Lyu, F. J.; Zhang, Y. F.; Zare, R. N.; Ge, J.; Liu, Z. One-pot synthesis of protein-embedded metal-organic frameworks with enhanced biological activities. Nano Lett. 2014, 14, 5761–5765.

    Article  ADS  CAS  PubMed  Google Scholar 

  30. Zheng, H. Q.; Zhang, Y. N.; Liu, L. F.; Wan, W.; Guo, P.; Nyström, A. M.; Zou, X. D. One-pot synthesis of metal-organic frameworks with encapsulated target molecules and their applications for controlled drug delivery. J. Am. Chem. Soc. 2016, 138, 962–968.

    Article  CAS  PubMed  Google Scholar 

  31. Li, F. L.; Chen, T.; Wang, F.; Chen, J. F.; Zhang, Y. Y.; Song, D. T.; Li, N.; Lin, X. H.; Lin, L. S.; Zhuang, J. Y. Enhanced cancer starvation therapy enabled by an autophagy inhibitors-encapsulated biomimetic ZIF-8 nanodrug: Disrupting and harnessing dual pro-survival autophagic responses. ACS Appl. Mater. Interfaces 2022, 14, 21860–21871.

    Article  CAS  PubMed  Google Scholar 

  32. Cheng, H.; Jiang, X. Y.; Zheng, R. R.; Zuo, S. J.; Zhao, L. P.; Fan, G. L.; Xie, B. R.; Yu, X. Y.; Li, S. Y.; Zhang, X. Z. A biomimetic cascade nanoreactor for tumor targeted starvation therapy-amplified chemotherapy. Biomaterials 2019, 195, 75–85.

    Article  CAS  PubMed  Google Scholar 

  33. Yang, J. C.; Chen, Y.; Li, Y. H.; Yin, X. B. Magnetic resonance imaging-guided multi-drug chemotherapy and photothermal synergistic therapy with pH and NIR-stimulation release. ACS Appl. Mater. Interfaces 2017, 9, 22278–22288.

    Article  CAS  PubMed  Google Scholar 

  34. Zou, B. H.; Xiong, Z. S.; He, L. Z.; Chen, T. F. Reversing breast cancer bone metastasis by metal organic framework-capped nanotherapeutics via suppressing osteoclastogenesis. Biomaterials 2022, 285, 121549.

    Article  CAS  PubMed  Google Scholar 

  35. Yang, W. S.; Stockwell, B. R. Ferroptosis: Death by lipid peroxidation. Trends Cell Biol. 2016, 26, 165–176.

    Article  CAS  PubMed  Google Scholar 

  36. Xie, Y.; Hou, W.; Song, X.; Yu, Y.; Huang, J.; Sun, X.; Kang, R.; Tang, D. Ferroptosis: Process and function. Cell Death Differ. 2016, 23, 369–379.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Liu, J.; Kang, R.; Tang, D. L. Signaling pathways and defense mechanisms of ferroptosis. FEBS J. 2022, 289, 7038–7050.

    Article  CAS  PubMed  Google Scholar 

  38. Weinhouse, S. The Warburg hypothesis fifty years later. Z. Krebsforsch. Klin. Onkol. Cancer Res. Clin. Oncol. 1976, 87, 115–126.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgement

This study was supported by the National Natural Science Foundation of China (No. 82002363), Natural Science Foundation of Chongqing, China (No. cstc2020jcyj-msxmX0195). All protocols of the animal study were approved by the Institutional Review Committee of Chongqing Medical University. Thanks to Ms. Xiaoyan Qin and Professor Ziguo Luo for their suggestions and guidance.

Author information

Author notes

  1. Jiandu Lei, Wei Jiang, and Zhenming Hu contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopedics, Orthopedic Laboratory of Chongqing Medical University, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Chongqing, 400010, China

    Miao Lei, Lin Chen, Shanlin Xiang, Wei Jiang & Zhenming Hu

  2. The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646699, China

    Weiye Cai & Chao Song

  3. Department of Orthopedics, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China

    Luetao Zou

  4. Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Chongqing, 400010, China

    Bin Yu

  5. Department of Orthopedics, Chongqing University Three Gorges Hospital, Chongqing, 404000, China

    Lin Chen

  6. Department of Geriatrics, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550025, China

    Yang Cao

  7. Beijing Key Laboratory of Lignocellulosic Chemistry, College of Material Science and Technology, Beijing Forestry University, Beijing, 100083, China

    Jiandu Lei

Authors
  1. Miao Lei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Weiye Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luetao Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bin Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yang Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shanlin Xiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Chao Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jiandu Lei
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Wei Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Zhenming Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jiandu Lei, Wei Jiang or Zhenming Hu.

Electronic Supplementary Material

12274_2023_5979_MOESM1_ESM.pdf

ZIF-8 coated gold nanospheres: a multi-responsive drug delivery system promoting the killing effect of photothermal therapy against osteosarcoma cells

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lei, M., Cai, W., Zou, L. et al. ZIF-8 coated gold nanospheres: a multi-responsive drug delivery system promoting the killing effect of photothermal therapy against osteosarcoma cells. Nano Res. 17, 1772–1784 (2024). https://doi.org/10.1007/s12274-023-5979-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12274-023-5979-1

Keywords

Search

Navigation