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


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.


  1. 1.

    Yun, S. H. & Kwok, S. J. J. Light in diagnosis, therapy and surgery. Nat. Biomed. Eng. 1, 0008 (2017).

    Article  Google Scholar 

  2. 2.

    Agostinis, P. et al. Photodynamic therapy of cancer: an update. CA Cancer J. Clin. 61, 250–281 (2011).

    Article  Google Scholar 

  3. 3.

    Mackenzie, G. D. et al. How light dosimetry influences the efficacy of photodynamic therapy with 5-aminolaevulinic acid for ablation of high-grade dysplasia in Barrett’s esophagus. Lasers Med. Sci. 23, 203–210 (2008).

    Article  Google Scholar 

  4. 4.

    Kinsey, J., Cortese, D. & Neel, H. Thermal considerations in murine tumour killing using hematoporphyrin derivative phototherapy. Cancer Res. 43, 1562–1567 (1983).

    CAS  PubMed  Google Scholar 

  5. 5.

    Horimatsu, T. et al. Tissue damage in the canine normal esophagus by photoactivation with talaporfin sodium (laserphyrin): a preclinical study. PLoS ONE 7, e38308 (2012).

    CAS  Article  Google Scholar 

  6. 6.

    Overholt, B. F. et al. Photodynamic therapy with porfimer sodium for ablation of high-grade dysplasia in Barrett’s esophagus: international, partially blinded, randomized phase III trial. Gastrointest. Endosc. 62, 488–498 (2005).

    Article  Google Scholar 

  7. 7.

    Wolfsen, H. C. et al. Clinical experience of patients undergoing photodynamic therapy for Barrett’s dysplasia or cancer. Aliment. Pharmacol. Ther. 20, 1125–1131 (2004).

    CAS  Article  Google Scholar 

  8. 8.

    Lam, S. et al. Photodynamic therapy with Photofrin®, a treatment with curative potential for early-stage superficial lung cancer. In Proc. 34th Annual Meeting of the American Society of Clinical Oncology (ASCO, Los Angeles, CA, 1998).

  9. 9.

    Istomin, Y. et al. Photodynamic therapy of cervical intraepithelial neoplasia grades II and III with Photolon®. Photodiagnosis Photodyn. Ther. 7, 144–151 (2010).

    CAS  Article  Google Scholar 

  10. 10.

    Choi, M. C. et al. Photodynamic therapy for management of cervical intraepithelial neoplasia II and III in young patients and obstetric outcomes. Lasers Surg. Med. 45, 564–572 (2013).

    Article  Google Scholar 

  11. 11.

    Bisland, S. K. et al. Metronomic photodynamic therapy as a new paradigm for photodynamic therapy: rationale and preclinical evaluation of technical feasibility for treating malignant brain tumours. Photochem. Photobiol. 80, 22–30 (2004).

    CAS  Article  Google Scholar 

  12. 12.

    Bruijn, S. De, Balbas, E. M., Sterenborg, H. J. C. M., French, P. J. & Robinson, D. J. A telemetric light delivery system for metronomic photodynamic therapy (mPDT) in rats. J. Biophotonics 3, 347–355 (2010).

    Article  Google Scholar 

  13. 13.

    Shin, G. et al. Fully implantable, battery-free wireless optoelectronic devices for spinal optogenetics. Pain 158, 2108–2116 (2017).

    Article  Google Scholar 

  14. 14.

    Samineni, V. K. et al. Injectable, cellular-scale optoelectronics with applications for wireless optogenetics. Science 340, 211–217 (2013).

    Article  Google Scholar 

  15. 15.

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

    CAS  Article  Google Scholar 

  16. 16.

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

    CAS  Article  Google Scholar 

  17. 17.

    Fujie, T., Okamura, Y. & Takeoka, S. Ubiquitous transference of a free-standing polysaccharide nanosheet with the development of a nano-adhesive plaster. Adv. Mater. 19, 3549–3553 (2007).

    CAS  Article  Google Scholar 

  18. 18.

    Fujie, T. Development of free-standing polymer nanosheets for advanced medical and health-care applications. Polymer J. 48, 773–780 (2016).

    CAS  Article  Google Scholar 

  19. 19.

    Lee, H., Scherer, N. F. & Messersmith, P. B. Single-molecule mechanics of mussel adhesion. Proc. Natl Acad. Sci. USA 103, 12999–13003 (2006).

    CAS  Article  Google Scholar 

  20. 20.

    Lee, H., Dellatore, S. M., Miller, W. M. & Messersmith, P. B. Mussel-inspired surface chemistry for multifunctional coatings. Science 318, 426–430 (2007).

    CAS  Article  Google Scholar 

  21. 21.

    Zucca, A. et al. Roll to roll processing of ultraconformable conducting polymer nanosheets. J. Mater. Chem. C 3, 6539–6548 (2015).

    CAS  Article  Google Scholar 

  22. 22.

    Fujie, T. et al. Adhesive, flexible, and robust polysaccharide nanosheets integrated for tissue-defect repair. Adv. Funct. Mater. 19, 2560–2568 (2009).

    CAS  Article  Google Scholar 

  23. 23.

    Kim, H. W. et al. Oxygen concentration control of dopamine-induced high uniformity surface coating chemistry. ACS Appl. Mater. Interfaces 5, 233–238 (2013).

    Article  Google Scholar 

  24. 24.

    Xue, P. et al. Surface modification of poly(dimethylsiloxane) with polydopamine and hyaluronic acid to enhance hemocompatibility for potential applications in medical implants or devices. ACS Appl. Mater. Interfaces 9, 33632 (2017).

    CAS  Article  Google Scholar 

  25. 25.

    Terry, B. S., Passernig, A. C., Hill, M. L., Schoen, J. A. & Rentschler, M. E. Small intestine mucosal adhesivity to in vivo capsule robot materials. J. Mech. Behav. Biomed. Mater. 15, 24–32 (2012).

    Article  Google Scholar 

  26. 26.

    Kaltenbrunner, M. et al. An ultra-lightweight design for imperceptible plastic electronics. Nature 499, 458–463 (2013).

    CAS  Article  Google Scholar 

  27. 27.

    Taniyama, T., Azuma, I., Aladin, A. A. & Yamamura, Y. Effect of cell-wall skeleton of Mycobacterium bovis BCG on cell-mediated cytotoxicity in tumour-bearing mice. Jpn J. Cancer Res. 66, 705–709 (1975).

    CAS  Google Scholar 

  28. 28.

    Mathews, M. S. et al. The effects of ultra low fluence rate single and repetitive photodynamic therapy on glioma spheroids. Lasers Surg. Med. 41, 578–584 (2009).

    Article  Google Scholar 

  29. 29.

    Bisland, S. K. et al. Metronomic photodynamic therapy as a new paradigm for photodynamic therapy: rationale and preclinical evaluation of technical feasibility for treating malignant brain tumours. Photochem. Photobiol. 80, 22–30 (2004).

    CAS  Article  Google Scholar 

  30. 30.

    Singh, G. et al. in Photodynamic Therapy: Methods and Protocols 1st edn (ed. Gomer, C. J.) 65–78 (Humana Press, New York, 2010).

  31. 31.

    Davies, N. & Wilson, B. C. Interstitial in vivo ALA-PpIX mediated metronomic photodynamic therapy (mPDT) using the CNS-1 astrocytoma with bioluminescence monitoring. Photodiagnostics Photodyn. Ther. 4, 202–212 (2007).

    CAS  Article  Google Scholar 

  32. 32.

    Bogaards, A. et al. Fluorescence image-guided brain tumour resection with adjuvant metronomic photodynamic therapy: pre-clinical model and technology development. Photochem. Photobiol. Sci. 4, 438–442 (2005).

    CAS  Article  Google Scholar 

  33. 33.

    Fernandez, J. M. et al. Singlet oxygen generation by photodynamic agents. J. Photochem. Photobiol. B 37, 131–140 (1997).

    CAS  Article  Google Scholar 

  34. 34.

    Hino, H., Murayama, Y. & Nakanishi, M. 5-Aminolevulinic acid-mediated photodynamic therapy using light-emitting diodes of different wavelengths in a mouse model of peritoneally disseminated gastric cancer. J. Surg. Res. 185, 119–126 (2013).

    CAS  Article  Google Scholar 

  35. 35.

    Fleischer, F. et al. Comparison of red and green light in the treatment of Bowen’s disease by photodynamic therapy. Br. J. Dermatol. 143, 767–772 (2000).

    Article  Google Scholar 

  36. 36.

    Fritsch, C. et al. Green light is effective and less painful than red light in photodynamic therapy of facial solar keratoses. Photodermatol. Photoimmunol. Photomed. 13, 181–185 (1997).

    CAS  Article  Google Scholar 

  37. 37.

    van Duijnhoven, F. H., Aalbers, R. I. J. M., Rovers, J. P., Terpstra, O. T. & Kuppen, P. J. K. The immunological consequences of photodynamic treatment of cancer, a literature review. Immunobiology 207, 105–113 (2003).

    CAS  Article  Google Scholar 

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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.

Author information




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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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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