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

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.

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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.

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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/.

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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.

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Authors and Affiliations

Authors

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.

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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.

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

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Supplementary information

Supplementary Information

Supplementary Figs. 1–48 and text.

Reporting Summary.

Supplementary Video 1

Freely behaving mice under wireless photothermal therapy.

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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

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