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Tissue-adhesive wirelessly powered optoelectronic device for metronomic photodynamic cancer therapy

Nature Biomedical Engineering volume 3, pages 27–36 (2019)Cite this article

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Abstract

Metronomic (that is, low-dose and long-term) photodynamic therapy (mPDT) for treating internal lesions requires the stable fixation of optical devices to internal tissue surfaces to enable continuous, local light delivery. Surgical suturing—the standard choice for device fixation—can be unsuitable in the presence of surrounding major nerves and blood vessels, as well as for organs or tissues that are fragile, change their shape or actively move. Here, we show that an implantable and wirelessly powered mPDT device consisting of near-field-communication-based light-emitting-diode chips and bioadhesive and stretchable polydopamine-modified poly(dimethylsiloxane) nanosheets can be stably fixed onto the inner surface of animal tissue. When implanted subcutaneously in mice with intradermally transplanted tumours, the device led to significant antitumour effects by irradiating for 10 d at approximately 1,000-fold lower intensity than conventional PDT approaches. The mPDT device might facilitate treatment strategies for hard-to-detect microtumours and deeply located lesions that are hard to reach with standard phototherapy.

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Fig. 1: Tissue-adhesive optoelectronics for implantable and wirelessly powered mPDT.
Fig. 2: Preparation and characterization of PDA–PDMS nanosheets.
Fig. 3: In vivo suture-free fixation of small IC tags.
Fig. 4: Fully implantable and wireless mPDT.

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Acknowledgements

This work was supported by the Leading Graduate Program in Science and Engineering, Waseda University from MEXT, Top Global University Program, Waseda University from MEXT, JSPS KAKENHI (grant numbers 15H05355, 15K15503 and 17K20116), a Grant-in-Aid for JSPS Fellows (grant number 16J07140), a Precursory Research for Embryonic Science and Technology (PRESTO) grant from the Japan Science and Technology Agency (JPMJPR152A), the Noguchi Institute and the Tanaka Memorial Foundation. The authors thank K. Iwasaki and X. Zhu (Waseda University) for valuable technical advice and X-ray transmission imaging observations; H. Miyazaki, D. Saitoh (National Defense Medical College), M. Kitajima (Waseda University) and F. Greco (Graz University of Technology) for valuable discussions; and W. Kayukawa, Y. Matsushita and T. Takee for technical assistance in cell culture.

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Authors and Affiliations

  1. Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan

    Kento Yamagishi, Isao Takahashi & Shinji Takeoka

  2. Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Izumi Kirino

  3. Institute of Advanced Active Aging Research, Waseda University, Tokyo, Japan

    Hizuru Amano

  4. Department of Pediatric Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Hizuru Amano

  5. Waseda Research Institute for Science and Engineering, Waseda University, Tokyo, Japan

    Shinji Takeoka

  6. Department of Physiology, National Defense Medical College, Saitama, Japan

    Yuji Morimoto

  7. Waseda Institute for Advanced Study, Waseda University, Tokyo, Japan

    Toshinori Fujie

  8. Japan Science and Technology Agency, PRESTO, Saitama, Japan

    Toshinori Fujie

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  1. Kento Yamagishi
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Contributions

S.T., Y.M. and T.F. jointly supervised this work. K.Y. and I.T. prepared and characterized the PDA–PDMS nanosheets. K.Y., I.K. and H.A. performed the in vivo experiments. K.Y., S.T., Y.M. and T.F. wrote the manuscript.

Corresponding authors

Correspondence to Yuji Morimoto or Toshinori Fujie.

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Competing interests

This work relates to patent PCT/JP201716283.

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Reporting Summary

Supplementary Video 1

LED emission in two mice implanted with a NFC-based red or green LED device.

Supplementary Video 2

Mouse bearing two red LED devices implanted under the dorsal skin.

Supplementary Video 3

Mouse bearing two green LED devices implanted under the dorsal skin.

Supplementary Video 4

Experimental set-up for a tack test to evaluate the adhesive energy between PDMS and chicken muscle.

Supplementary Video 5

Intradermal injection of cancer cells (Colon-26) in the dorsal skin of a mouse.

Supplementary Video 6

Implanted LED device on the inner surface of the dorsal skin (opened skin) remains in position when the skin is stretched, compressed and twisted.

Supplementary Video 7

Implanted LED device on the inner surface of the dorsal skin (closed skin) remains in position when the skin is stretched, compressed and twisted.

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Yamagishi, K., Kirino, I., Takahashi, I. et al. Tissue-adhesive wirelessly powered optoelectronic device for metronomic photodynamic cancer therapy. Nat Biomed Eng 3, 27–36 (2019). https://doi.org/10.1038/s41551-018-0261-7

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