Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Remotely controlled near-infrared-triggered photothermal treatment of brain tumours in freely behaving mice using gold nanostars

Nature Nanotechnology volume 17, pages 1015–1022 (2022)Cite this article

Subjects

Abstract

Current clinical brain tumour therapy practices are based on tumour resection and post-operative chemotherapy or X-ray radiation. Resection requires technically challenging open-skull surgeries that can lead to major neurological deficits and, in some cases, death. Treatments with X-ray and chemotherapy, on the other hand, cause major side-effects such as damage to surrounding normal brain tissues and other organs. Here we report the development of an integrated nanomedicine–bioelectronics brain–machine interface that enables continuous and on-demand treatment of brain tumours, without open-skull surgery and toxicological side-effects on other organs. Near-infrared surface plasmon characteristics of our gold nanostars enabled the precise treatment of deep brain tumours in freely behaving mice. Moreover, the nanostars’ surface coating enabled their selective diffusion in tumour tissues after intratumoral administration, leading to the exclusive heating of tumours for treatment. This versatile remotely controlled and wireless method allows the adjustment of nanoparticles’ photothermal strength, as well as power and wavelength of the therapeutic light, to target tumours in different anatomical locations within the brain.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Nanoparticle design for photothermal heating of brain tumours.
Fig. 2: Designing duty-cycled NIR-emitting devices for remote-controlled triggering of nanoparticles’ photothermal effect in the brain over a long-term (15 days) treatment cycle.
Fig. 3: Tuning wireless power transfer efficiency and evaluating safety for photothermal therapy in freely behaving mice.
Fig. 4: Wireless photothermal therapy of brain tumours in freely behaving mice.

Data availability

The data supporting the findings of this study are available within the paper and its Supplementary Information files and are available from the corresponding authors upon reasonable request.

Code availability

The custom script prepared for the wireless photothermal therapy performed in this study is available to download from https://osf.io/5vqxc/.

References

  1. Ostrom, Q. T. et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2013–2017. Neuro Oncol. 22, iv1–iv96 (2020).

    Article  Google Scholar 

  2. Stupp, R. et al. Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA 318, 2306–2316 (2017).

    Article  CAS  Google Scholar 

  3. Kok, H. P. et al. Heating technology for malignant tumors: a review. Int. J. Hyperth. 37, 711–741 (2020).

    Article  CAS  Google Scholar 

  4. Bastiancich, C., Da Silva, A. & Esteve, M. A. Photothermal therapy for the treatment of glioblastoma: potential and preclinical challenges. Front. Oncol. 10, 610356 (2020).

    Article  Google Scholar 

  5. Pinto, A. & Pocard, M. Photodynamic therapy and photothermal therapy for the treatment of peritoneal metastasis: a systematic review. Pleura Peritoneum 3, 20180124 (2018).

    Article  Google Scholar 

  6. Wei, Q. et al. Intraoperative assessment and photothermal ablation of the tumor margins using gold nanoparticles. Adv. Sci. 8, 2002788 (2021).

    Article  CAS  Google Scholar 

  7. Pinel, S., Thomas, N., Boura, C. & Barberi-Heyob, M. Approaches to physical stimulation of metallic nanoparticles for glioblastoma treatment. Adv. Drug Deliv. Rev. 138, 344–357 (2019).

    Article  CAS  Google Scholar 

  8. Vines, J. B., Yoon, J. H., Ryu, N. E., Lim, D. J. & Park, H. Gold nanoparticles for photothermal cancer therapy. Front. Chem. 7, 167 (2019).

    Article  CAS  Google Scholar 

  9. Chatterjee, H., Rahman, D. S., Sengupta, M. & Ghosh, S. K. Gold nanostars in plasmonic photothermal therapy: the role of tip heads in the thermoplasmonic landscape. J. Phys. Chem. C 122, 13082–13094 (2018).

    Article  CAS  Google Scholar 

  10. Vo-Dinh, T. et al. Shining gold nanostars: from cancer diagnostics to photothermal treatment and immunotherapy. J. Immunol. Sci. 2, 1–8 (2018).

    Article  Google Scholar 

  11. Arami, H. et al. Nanomedicine for spontaneous brain tumors: a companion clinical trial. ACS Nano 13, 2858–2869 (2019).

    Article  CAS  Google Scholar 

  12. Kim, T. I. et al. Injectable, cellular-scale optoelectronics with applications for wireless optogenetics. Science 340, 211–216 (2013).

    Article  CAS  Google Scholar 

  13. Montgomery, K. L. et al. Wirelessly powered, fully internal optogenetics for brain, spinal and peripheral circuits in mice. Nat. Methods 12, 969–974 (2015).

    Article  CAS  Google Scholar 

  14. Park, S. I. et al. Soft, stretchable, fully implantable miniaturized optoelectronic systems for wireless optogenetics. Nat. Biotechnol. 33, 1280–1286 (2015).

    Article  CAS  Google Scholar 

  15. Kang, S. K. et al. Bioresorbable silicon electronic sensors for the brain. Nature 530, 71–76 (2016).

    Article  CAS  Google Scholar 

  16. Chung, H. U. et al. Binodal, wireless epidermal electronic systems with in-sensor analytics for neonatal intensive care. Science 363, eaau0780 (2019).

  17. Lee, Y. & Kim, D. H. Wireless metronomic photodynamic therapy. Nat. Biomed. Eng. 3, 5–6 (2019).

    Article  Google Scholar 

  18. Yamagishi, K. et al. Tissue-adhesive wirelessly powered optoelectronic device for metronomic photodynamic cancer therapy. Nat. Biomed. Eng. 3, 27–36 (2019).

    Article  CAS  Google Scholar 

  19. Agrawal, D. R. et al. Conformal phased surfaces for wireless powering of bioelectronic microdevices. Nat. Biomed. Eng. 1, 0043 (2017).

  20. Bansal, A., Yang, F., Xi, T., Zhang, Y. & Ho, J. S. In vivo wireless photonic photodynamic therapy. Proc. Natl Acad. Sci. USA 115, 1469–1474 (2018).

    Article  CAS  Google Scholar 

  21. Ho, J. S. et al. Self-tracking energy transfer for neural stimulation in untethered mice. Phys. Rev. Appl. 4, 024001 (2015).

    Article  Google Scholar 

  22. Wang, M., Kim, M., Xia, F. & Xu, C. Impact of the emission wavelengths on in vivo multiphoton imaging of mouse brains. Biomed. Opt. Express 10, 1905–1918 (2019).

    Article  CAS  Google Scholar 

  23. Stujenske, J. M., Spellman, T. & Gordon, J. A. Modeling the spatiotemporal dynamics of light and heat propagation for in vivo optogenetics. Cell Rep. 12, 525–534 (2015).

    Article  CAS  Google Scholar 

  24. Lee, P. M., Tian, X. & Ho, J. S. Wireless power transfer for glioblastoma photodynamic therapy. In 2019 IEEE Biomedical Circuits and Systems Conference (BioCAS) 1–4 (IEEE, 2019).

  25. US Federal Communications Commission. 47 CFR 1.1310, Radiofrequency radiation exposure limits (Federal Communications Commission, Washington, DC, 2011).

  26. Ash, C., Dubec, M., Donne, K. & Bashford, T. Effect of wavelength and beam width on penetration in light-tissue interaction using computational methods. Lasers Med. Sci. 32, 1909–1918 (2017).

    Article  Google Scholar 

  27. Gutruf, P. et al. Wireless, battery-free, fully implantable multimodal and multisite pacemakers for applications in small animal models. Nat. Commun. 10, 5742 (2019).

    Article  CAS  Google Scholar 

  28. Shin, G. et al. Flexible near-field wireless optoelectronics as subdermal implants for broad applications in optogenetics. Neuron 93, 509–521.e3 (2017).

    Article  CAS  Google Scholar 

  29. Kim, A. et al. An implantable ultrasonically-powered micro-light-source (µLight) for photodynamic therapy. Sci. Rep. 9, 1395 (2019).

    Article  Google Scholar 

  30. Tajima, K. et al. Wireless optogenetics protects against obesity via stimulation of non-canonical fat thermogenesis. Nat. Commun. 11, 1730 (2020).

    Article  CAS  Google Scholar 

  31. Holland, J. M., Mitchell, T. J., Gipson, L. C. & Whitaker, M. S. Survival and cause of death in aging germfree athymic nude and normal inbred C3Hf/He mice. J. Natl Cancer Inst. 61, 1357–1361 (1978).

    Article  CAS  Google Scholar 

  32. Simpson, J. R. et al. Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials. Int. J. Radiat. Oncol. Biol. Phys. 26, 239–244 (1993).

    Article  CAS  Google Scholar 

  33. Hettie, K. S., Teraphongphom, N. T., Ertsey, R. D., Rosenthal, E. L. & Chin, F. T. Targeting intracranial patient-derived glioblastoma (GBM) with a NIR-I fluorescent immunoconjugate for facilitating its image-guided resection. RSC Adv. 10, 42413–42422 (2020).

    Article  CAS  Google Scholar 

  34. Chang, E. et al. AshwaMAX and Withaferin A inhibits gliomas in cellular and murine orthotopic models. J. Neurooncol. 126, 253–264 (2016).

    Article  CAS  Google Scholar 

  35. Won, S. M., Song, E., Reeder, J. T. & Rogers, J. A. Emerging modalities and implantable technologies for neuromodulation. Cell 181, 115–135 (2020).

    Article  CAS  Google Scholar 

  36. Kim, J., Campbell, A. S., de Avila, B. E. & Wang, J. Wearable biosensors for healthcare monitoring. Nat. Biotechnol. 37, 389–406 (2019).

    Article  CAS  Google Scholar 

  37. Yang, J. C. et al. Electronic skin: recent progress and future prospects for skin-attachable devices for health monitoring, robotics, and prosthetics. Adv. Mater. 31, e1904765 (2019).

    Article  Google Scholar 

  38. Pucci, C., Martinelli, C. & Ciofani, G. Innovative approaches for cancer treatment: current perspectives and new challenges. Ecancermedicalscience 13, 961 (2019).

    Article  Google Scholar 

  39. Murty, S. et al. Intravital imaging reveals synergistic effect of CAR T-cells and radiation therapy in a preclinical immunocompetent glioblastoma model. OncoImmunology 9, 1757360 (2020).

    Article  Google Scholar 

  40. Tavares, A. J. et al. Effect of removing Kupffer cells on nanoparticle tumor delivery. Proc. Natl Acad. Sci. USA 114, E10871–E10880 (2017).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We acknowledge support from the Center for Cancer Nanotechnology Excellence and Translation at NCI-NIH (grant no. 1U54CA199075) and NIH grants (NCI 1R01CA199656-01A1 and 1R01 222836-01). H.A. was supported by NIH National Cancer Institute K99/R00 Pathway to Independence award (grant no. 1K99CA234208-01A1) and NIH T32 CA009695 (Stanford Cancer Imaging Training, SCIT). L.K. acknowledges support from the NIH National Institute of Biomedical Imaging and Bioengineering (NIBIB) K99/R00 Pathway to Independence award (grant no. 1K99EB031178-01) and NIH T32 CA196585 (Cancer-Translational Nanotechnology Training (Cancer-TNT) program) at Stanford University. C.B.P. is a McNair Scholar supported by the McNair Medical Institute at The Robert and Janice McNair Foundation. We thank I. V. Balyasnikova at Northwestern University and M. D. Ferro at Stanford University for providing the U87-GFP-Fluc cells and assistance with parylene coating, respectively. Additionally, we acknowledge CST for providing access to the 3D full-wave simulator (CST Studio Suite). We also thank support and guidance from J. Rao and H. Daldrup-Link at Stanford Department of Radiology that enabled us to complete this study. This paper is dedicated to Dr. Sanjiv Sam Gambhir, who we lost to cancer during the preparation of this manuscript.

Author information

Author notes

  1. These authors contributed equally: Hamed Arami, Siavash Kananian, Layla Khalifehzadeh.

  2. This paper is dedicated to Sanjiv Sam Gambhir, whom we lost to cancer during the preparation of this manuscript.

Authors and Affiliations

  1. Department of Radiology, Molecular Imaging Program at Stanford, Stanford School of Medicine, Stanford, CA, USA

    Hamed Arami, Chirag B. Patel, Edwin Chang, Michael J. Mandella, Arutselvan Natarajan & Sanjiv Sam Gambhir

  2. Department of Electrical Engineering, Stanford University, Stanford, CA, USA

    Siavash Kananian, Yuji Tanabe & Ada S. Y. Poon

  3. Department of Chemical Engineering, Stanford University, Stanford, CA, USA

    Layla Khalifehzadeh

  4. Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Chirag B. Patel

  5. Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences (GSBS), Houston, TX, USA

    Chirag B. Patel

  6. Aeterlink, Chiyoda City, Japan

    Yuji Tanabe

  7. AET, Chiyoda City, Japan

    Yuji Tanabe

  8. Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA

    Yitian Zeng, Steven J. Madsen & Robert Sinclair

  9. Department of Comparative Medicine, Stanford School of Medicine, Stanford, CA, USA

    Eric E. Peterson

  10. Chan Zuckerberg Biohub, San Francisco, CA, USA

    Ada S. Y. Poon

  11. Department of Bioengineering, Stanford University, Stanford, CA, USA

    Sanjiv Sam Gambhir

Authors
  1. Hamed Arami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Siavash Kananian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Layla Khalifehzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chirag B. Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Edwin Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yuji Tanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yitian Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Steven J. Madsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Michael J. Mandella
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Arutselvan Natarajan
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Eric E. Peterson
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Robert Sinclair
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Ada S. Y. Poon
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Sanjiv Sam Gambhir
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

H.A. developed the idea, carried out or supervised all the experiments, analysed the data and wrote the manuscript. H.A., S.K. and L.K. designed the project and experiments and contributed to the data analysis and manuscript revision. C.B.P., E.C. and A.N. contributed to the animal experiments, imaging and histological data analysis. E.E.P. helped with tissue processing and histological experiments. Y.T. and A.S.Y.P discussed and supervised the design of the wireless systems. Y.Z., S.J.M. and R.S. performed the SEM measurements. M.J.M. contributed in designing the optical devices. All the authors reviewed and commented on the manuscript. S.S.G. and A.S.Y.P discussed and supervised the experiments and manuscript preparation.

Corresponding authors

Correspondence to Hamed Arami or Ada S. Y. Poon.

Ethics declarations

Competing interests

The authors declare the following competing interests: A.S.Y.P. and Y.T. co-founded Aeterlink and Vivonda Medical commercializing wireless powering technology. H.A., S.K., L.K., M.J.M., A.S.Y.P. and S.S.G are the co-inventors of a patent covering this study filed by Stanford University. All the other authors have no competing interests.

Peer review

Peer review information

Nature Nanotechnology thanks Constantinos Hadjipanayis, John Ho and Rodney O’Connor for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Figs. 1–48 and text.

Reporting Summary.

Supplementary Video 1

Freely behaving mice under wireless photothermal therapy.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Arami, H., Kananian, S., Khalifehzadeh, L. et al. Remotely controlled near-infrared-triggered photothermal treatment of brain tumours in freely behaving mice using gold nanostars. Nat. Nanotechnol. 17, 1015–1022 (2022). https://doi.org/10.1038/s41565-022-01189-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41565-022-01189-y

This article is cited by

Search

Advanced search

Quick links

Find nanotechnology articles, nanomaterial data and patents all in one place. Visit Nano by Nature Research