Skip to main content

Near-infrared Transillumination and Photodynamic Therapy Using Hypericin in Animal Laryngeal Tumors

Abstract

Background:

We aimed to validate a pilot study of photodiagnosis using near infrared (NIR) transillumination and assess the clinical efficacy of hypericin-mediated photodynamic therapy (HYP-PDT) in a rabbit laryngeal cancer model in order to develop a novel therapeutic modality with complete remission and preservation of the functional organ.

Methods:

(1) In vitro study: VX tumor cells were subcultured and subjected to HYP-PDT. (2) In vivo study: A laryngeal cancer model was developed in which 12 rabbits were inoculated with a VX tumor suspension in the submucosal area of the left vocal fold using a transoral approach. All rabbits underwent NIR transillumination using light with a wavelength of 780 nm. The survival periods of the three treatment groups (6 rabbits in Group A: HYP-PDT, 3 each in Groups B and C: laser irradiation or HYP administration only) were analyzed.

Results:

The higher the HYP concentration, the lower the VX cell viability in response to HYP-PDT using 590 nm LED. Following HYP-PDT, small tumors in Group A-1 rabbits healed completely and the animals demonstrated a long survival period, and larger tumors in Group A-2 healed partially with a survival period that extended over 3 weeks after inoculation. The survival of Groups B and C were not different over the first 3 weeks of the study, and were shorter than in Group A.

Conclusion:

We found HYP-PDT could be a curative therapy for early-stage cancers that may also preserve organ function, and may inhibit tumor progression and metastasis during advanced stages of laryngeal cancer.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13

References

  1. 1.

    Nakayama M, Laccourreye O, Holsinger FC, Okamoto M, Hayakawa K. Functional organ preservation for laryngeal cancer: past, present and future. Jpn J Clin Oncol. 2012;42:155–60.

    Article  Google Scholar 

  2. 2.

    von Beckerath MP, Reizenstein JA, Berner AL, Nordqvist KW, Landström FJ, Löfgren AL, et al. Outcome of primary treatment of early laryngeal malignancies using photodynamic therapy. Acta Otolaryngol. 2014;134:852–8.

    Article  Google Scholar 

  3. 3.

    Choi JS, Oh SH, Kim YM, Lim JY. Hyaluronic acid/alginate hydrogel containing hepatocyte growth factor and promotion of vocal fold wound healing. Tissue Eng Regen Med. 2020;17:651–8.

    CAS  Article  Google Scholar 

  4. 4.

    Jung SY, Tran AN, Kim HY, Choi E, Lee SJ, Kim HS. Development of acellular respiratory mucosal matrix using porcine tracheal mucosa. Tissue Eng Regen Med. 2020;17:433–43.

    CAS  Article  Google Scholar 

  5. 5.

    Xin Z, Kim SW, Oak C, Kwon DY, Choi JH, Ko TY, et al. Investigation of the clinical potential of polarization-sensitive optical coherence tomography in a laryngeal tumor model. Tissue Eng Regen Med. 2021;18:81–7.

    CAS  Article  Google Scholar 

  6. 6.

    Oak C, Ahn YC, Nam SJ, Jung MH, Hwang SS, Chae YG, et al. Multimodal imaging using optical coherence tomography and endolaryngeal ultrasonography in a new rabbit VX2 laryngeal cancer model. Lasers Surg Med. 2015;47:704–10.

    Article  Google Scholar 

  7. 7.

    Mahmood U, Cerussi A, Dehdari R, Nguyen Q, Kelley T, Tromberg B, et al. Near-infrared imaging of the sinuses: preliminary evaluation of a new technology for diagnosing maxillary sinusitis. J Biomed Opt. 2010;15:036011.

    Article  Google Scholar 

  8. 8.

    Tao YC, Fried D. Near-infrared image-guided laser ablation of dental decay. J Biomed Opt. 2009;14:054045.

    Article  Google Scholar 

  9. 9.

    Cerussi AE, Mishra N, You J, Bhandarkar N, Wong B. Monte Carlo modeling of light propagation in the human head for applications in sinus imaging. J Biomed Opt. 2015;20:035004.

    Article  Google Scholar 

  10. 10.

    Castano AP, Demidova TN, Hamblin MR. Mechanisms in photodynamic therapy: part two-cellular signaling, cell metabolism and modes of cell death. Photodiagnosis Photodyn Ther. 2005;2:1–23.

    CAS  Article  Google Scholar 

  11. 11.

    Thomas C, MacGill RS, Miller GC, Pardini RS. Photoactivation of hypericin generates singlet oxygen in mitochondria and inhibits succinoxidase. Photochem Photobiol. 1992;55:47–53.

    CAS  Article  Google Scholar 

  12. 12.

    Thomas C, Pardini RS. Oxygen dependence of hypericin-induced phototoxicity to EMT6 mouse mammary carcinoma cells. Photochem Photobiol. 1992;55:831–7.

    CAS  Article  Google Scholar 

  13. 13.

    Stupáková V, Varinská L, Mirossay A, Sarisský M, Mojzis J, Dankovcík R, et al. Photodynamic effect of hypericin in primary cultures of human umbilical endothelial cells and glioma cell lines. Phytother Res. 2009;23:827–32.

    Article  Google Scholar 

  14. 14.

    Seitz G, Krause R, Fuchs J, Heitmann H, Armeanu S, Ruck P, et al. In vitro photodynamic therapy in pediatric epithelial liver tumors promoted by hypericin. Oncol Rep. 2008;20:1277–82.

    CAS  PubMed  Google Scholar 

  15. 15.

    Li L, Huang T, Liu H, Zang J, Wang P, Jiang X. Purification, structural characterization and anti-UVB irradiation activity of an extracellular polysaccharide from Pantoea agglomerans. Int J Biol Macromol. 2019;137:1002–12.

    CAS  Article  Google Scholar 

  16. 16.

    Wessels JT, Busse AC, Rave-Fränk M, Zänker S, Hermann R, Grabbe E, et al. Photosensitizing and radiosensitizing effects of hypericin on human renal carcinoma cells in vitro. Photochem Photobiol. 2008;84:228–35.

    CAS  PubMed  Google Scholar 

  17. 17.

    Seitz G, Warmann SW, Armeanu S, Heitmann H, Ruck P, Hoffman RM, et al. In vitro photodynamic therapy of childhood rhabdomyosarcoma. Int J Oncol. 2007;30:615–20.

    CAS  PubMed  Google Scholar 

  18. 18.

    Berlanda J, Kiesslich T, Oberdanner CB, Obermair FJ, Krammer B, Plaetzer K. Characterization of apoptosis induced by photodynamic treatment with hypericin in A431 human epidermoid carcinoma cells. J Environ Pathol Toxicol Oncol. 2006;25:173–88.

    CAS  Article  Google Scholar 

  19. 19.

    Blank M, Lavie G, Mandel M, Hazan S, Orenstein A, Meruelo D, et al. Antimetastatic activity of the photodynamic agent hypericin in the dark. Int J Cancer. 2004;111:596–603.

    CAS  Article  Google Scholar 

  20. 20.

    Hanna NM, Waite W, Taylor K, Jung WG, Mukai D, Matheny E, et al. Feasibility of three-dimensional optical coherence tomography and optical Doppler tomography of malignancy in hamster cheek pouches. Photomed Laser Surg. 2006;24:402–9.

    Article  Google Scholar 

  21. 21.

    Yoneda T, Kitamura M, Ogawa T, Aya S, Sakuda M. Control of VX2 carcinoma cell growth in culture by calcium, calmodulin, and prostaglandins. Cancer Res. 1985;45:398–405.

    CAS  PubMed  Google Scholar 

  22. 22.

    Thibaut S, Bourré L, Hernot D, Rousset N, Lajat Y, Patrice T. Effects of BAPTA-AM, Forskolin, DSF and Z.VAD.fmk on PDT-induced apoptosis and m-THPC phototoxicity on B16 cells. Apoptosis. 2002;7:99–106.

    CAS  Article  Google Scholar 

Download references

Acknowledgement

This study was supported by a grant from the National Research Foundation of Korea (NRF-2019M3E5D1A02070860).

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Yeh-Chan Ahn or Chulho Oak.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

The animal studies were performed after receiving approval of the Institutional Animal Care and Use Committee (IACUS) at Kosin University College of Medicine (IACUC approval No. KMAP 15-07).

Additional information

Publisher's Note

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

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Lee, H., Kim, S.W., Kwon, D.Y. et al. Near-infrared Transillumination and Photodynamic Therapy Using Hypericin in Animal Laryngeal Tumors. Tissue Eng Regen Med (2021). https://doi.org/10.1007/s13770-021-00377-6

Download citation

Keywords

  • Hypericin
  • Photodynamic therapy
  • Laryngeal cancer