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Targeted photodynamic therapy in head and neck squamous cell carcinoma: heading into the future

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Abstract

The aim of this article is to give an insight into the future of photodynamic therapy (PDT) in head and neck squamous cell carcinoma (HNSCC). Through the combination of a photosensitizing agent with light and oxygen, PDT produces highly cytotoxic reactive oxygen species leading to selective tumor eradication. PDT is an attractive treatment for focal therapy of localized tumors, especially in the case of unresectable tumors. In HNSCC, over 1500 patients have been treated by PDT, and the majority of them responded quite favorably to this treatment. However, the non-negligible photosensitization of healthy tissue is a major limitation for the clinical application of PDT. Improvement in tumor selectivity is the main challenge that can be taken up by the use of a new generation of photosensitizing nanoparticles. Passive targeting, by using functionalised nanocarriers to target to overexpressed transmembrane receptors afford attractive solutions. To this day, epidermal growth factor receptor (EGFR) remains the only validated molecular target for HNSCC, and photosensitizer immunoconjugates to EGFR have been developed for the intracellular delivery of photosensitizing agents. Depending on coordinated research between biomarkers, specific ligands, and photosensitizers, similar approaches could be rapidly developed. In addition, some photosensitizers hold high fluorescence yield and therefore could emerge as theranostic agents.

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References

  1. Argiris A, Karamouzis MV, Raben D, Ferris RL (2008) Head and neck cancer. Lancet 371:1695–1709

    Article  CAS  PubMed  Google Scholar 

  2. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62:10–29

    Article  PubMed  Google Scholar 

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

    Article  PubMed Central  PubMed  Google Scholar 

  4. Bredell MG, Besic E, Maake C, Walt H (2010) The application and challenges of clinical PD-PDT in the head and neck region: a short review. J Photochem Photobiol B 101:185–190

    Article  CAS  PubMed  Google Scholar 

  5. Bonner JA, Harari PM, Giralt J et al (2010) Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 11:21–28

    Article  CAS  PubMed  Google Scholar 

  6. Reuther T, Kubler AC, Zillmann U et al (2001) Comparison of the in vivo efficiency of photofrin II-, mTHPC-, mTHPC-PEG- and mTHPCnPEG-mediated PDT in a human xenografted head and neck carcinoma. Lasers Surg Med 29:314–322

    Article  CAS  PubMed  Google Scholar 

  7. Biel MA (2010) Photodynamic therapy of head and neck cancers. Methods Mol Biol 635:281–293

    Article  PubMed  Google Scholar 

  8. Schweitzer VG, Somers ML (2010) PHOTOFRIN-mediated photodynamic therapy for treatment of early stage (Tis-T2N0M0) SqCCa of oral cavity and oropharynx. Lasers Surg Med 42:1–8

    Article  PubMed  Google Scholar 

  9. de Visscher SA, Dijkstra PU, Tan IB et al (2013) mTHPC mediated photodynamic therapy (PDT) of squamous cell carcinoma in the head and neck: a systematic review. Oral Oncol 49:192–210

    Article  PubMed  Google Scholar 

  10. Jerjes W, Upile T, Hamdoon Z et al (2011) Photodynamic therapy outcome for T1/T2 N0 oral squamous cell carcinoma. Lasers Surg Med 43:463–469

    Article  PubMed  Google Scholar 

  11. Karakullukcu B, Stoker SD, Wildeman AP et al (2013) A matched cohort comparison of mTHPC-mediated photodynamic therapy and trans-oral surgery of early stage oral cavity squamous cell cancer. Eur Arch Otorhinolaryngol 270:1093–1097

    Article  PubMed Central  PubMed  Google Scholar 

  12. Tan IB, Dolivet G, Ceruse P et al (2010) Temoporfin-mediated photodynamic therapy in patients with advanced, incurable head and neck cancer: a multicenter study. Head Neck 32:1597–1604

    Article  PubMed  Google Scholar 

  13. Jerjes W, Upile T, Akram S, Hopper C (2010) The surgical palliation of advanced head and neck cancer using photodynamic therapy. Clin Oncol (R Coll Radiol) 22:785–791

    Article  CAS  Google Scholar 

  14. Karakullukcu B, Nyst HJ, van Veen RL et al (2012) mTHPC mediated interstitial photodynamic therapy of recurrent nonmetastatic base of tongue cancers: development of a new method. Head Neck 34:1597–1606

    Article  PubMed  Google Scholar 

  15. Berg K, Folini M, Prasmickaite L et al (2007) Photochemical internalization: a new tool for drug delivery. Curr Pharm Biotechnol 8:362–372

    Article  CAS  PubMed  Google Scholar 

  16. Berg K, Nordstrand S, Selbo PK et al (2011) Disulfonated tetraphenyl chlorin (TPCS2a), a novel photosensitizer developed for clinical utilization of photochemical internalization. Photochem Photobiol Sci 10:1637–1651

    Article  CAS  PubMed  Google Scholar 

  17. Morrison SA, Hill SL, Rogers GS, Graham RA (2014) Efficacy and safety of continuous low-irradiance photodynamic therapy in the treatment of chest wall progression of breast cancer. J Surg Res 192:235–241

    Article  CAS  PubMed  Google Scholar 

  18. Wang HW, Rickter E, Yuan M et al (2007) Effect of photosensitizer dose on fluence rate responses to photodynamic therapy. Photochem Photobiol 83:1040–1048

    Article  CAS  PubMed  Google Scholar 

  19. Henderson BW, Gollnick SO, Snyder JW et al (2004) Choice of oxygen-conserving treatment regimen determines the inflammatory response and outcome of photodynamic therapy of tumors. Cancer Res 64:2120–2126

    Article  CAS  PubMed  Google Scholar 

  20. Garrier J, Bressenot A, Grafe S et al (2010) Compartmental targeting for mTHPC-based photodynamic treatment in vivo: correlation of efficiency, pharmacokinetics, and regional distribution of apoptosis. Int J Radiat Oncol Biol Phys 78:563–571

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Bugaj AM (2011) Targeted photodynamic therapy—a promising strategy of tumor treatment. Photochem Photobiol Sci 10:1097–1109

    Article  CAS  PubMed  Google Scholar 

  22. Lim CK, Heo J, Shin S et al (2013) Nanophotosensitizers toward advanced photodynamic therapy of cancer. Cancer Lett 334:176–187

    Article  CAS  PubMed  Google Scholar 

  23. Master A, Livingston M, Sen Gupta A (2013) Photodynamic nanomedicine in the treatment of solid tumors: perspectives and challenges. J Control Release 168:88–102

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Ernsting MJ, Murakami M, Roy A, Li SD (2013) Factors controlling the pharmacokinetics, biodistribution and intratumoral penetration of nanoparticles. J Control Release 172:782–794

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Buchholz J, Wergin M, Walt H et al (2007) Photodynamic therapy of feline cutaneous squamous cell carcinoma using a newly developed liposomal photosensitizer: preliminary results concerning drug safety and efficacy. J Vet Intern Med 21:770–775

    Article  PubMed  Google Scholar 

  26. Buchholz J, Kaser-Hotz B, Khan T et al (2005) Optimizing photodynamic therapy: in vivo pharmacokinetics of liposomal meta-(tetrahydroxyphenyl)chlorin in feline squamous cell carcinoma. Clin Cancer Res 11:7538–7544

    Article  CAS  PubMed  Google Scholar 

  27. de Visscher SA, Kascakova S, de Bruijn HS et al (2011) Fluorescence localization and kinetics of mTHPC and liposomal formulations of mTHPC in the window-chamber tumor model. Lasers Surg Med 43:528–536

    Article  PubMed  Google Scholar 

  28. Lassalle HP, Dumas D, Grafe S et al (2009) Correlation between in vivo pharmacokinetics, intratumoral distribution and photodynamic efficiency of liposomal mTHPC. J Control Release 134:118–124

    Article  CAS  PubMed  Google Scholar 

  29. Bovis MJ, Woodhams JH, Loizidou M et al (2012) Improved in vivo delivery of m-THPC via pegylated liposomes for use in photodynamic therapy. J Control Release 157:196–205

    Article  CAS  PubMed  Google Scholar 

  30. Igarashi A, Konno H, Tanaka T et al (2003) Liposomal photofrin enhances therapeutic efficacy of photodynamic therapy against the human gastric cancer. Toxicol Lett 145:133–141

    Article  CAS  PubMed  Google Scholar 

  31. Hofman JW, Carstens MG, van Zeeland F et al (2008) Photocytotoxicity of mTHPC (temoporfin) loaded polymeric micelles mediated by lipase catalyzed degradation. Pharm Res 25:2065–2073

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Low K, Knobloch T, Wagner S et al (2011) Comparison of intracellular accumulation and cytotoxicity of free mTHPC and mTHPC-loaded PLGA nanoparticles in human colon carcinoma cells. Nanotechnology 22:245102

    Article  PubMed  Google Scholar 

  33. Rojnik M, Kocbek P, Moret F et al (2012) In vitro and in vivo characterization of temoporfin-loaded PEGylated PLGA nanoparticles for use in photodynamic therapy. Nanomedicine (Lond) 7:663–677

    Article  CAS  Google Scholar 

  34. Lee SJ, Park K, Oh YK et al (2009) Tumor specificity and therapeutic efficacy of photosensitizer-encapsulated glycol chitosan-based nanoparticles in tumor-bearing mice. Biomaterials 30:2929–2939

    Article  CAS  PubMed  Google Scholar 

  35. Yang PW, Hung MC, Hsieh CY et al (2012) The effects of photofrin-mediated photodynamic therapy on the modulation of EGFR in esophageal squamous cell carcinoma cells. Lasers Med Sci 28:605–614

    Article  PubMed  Google Scholar 

  36. Martinez-Carpio PA, Trelles MA (2010) The role of epidermal growth factor receptor in photodynamic therapy: a review of the literature and proposal for future investigation. Lasers Med Sci 25:767–771

    Article  PubMed  Google Scholar 

  37. Edmonds C, Hagan S, Gallagher-Colombo SM et al (2012) Photodynamic therapy activated signaling from epidermal growth factor receptor and STAT3: targeting survival pathways to increase PDT efficacy in ovarian and lung cancer. Cancer Biol Ther 13:1463–1470

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Jin CS, Zheng G (2011) Liposomal nanostructures for photosensitizer delivery. Lasers Surg Med 43:734–748

    Article  PubMed  Google Scholar 

  39. Gijsens A, Missiaen L, Merlevede W, de Witte P (2000) Epidermal growth factor-mediated targeting of chlorin e6 selectively potentiates its photodynamic activity. Cancer Res 60:2197–2202

    CAS  PubMed  Google Scholar 

  40. Hemming AW, Davis NL, Dubois B et al (1993) Photodynamic therapy of squamous cell carcinoma. An evaluation of a new photosensitizing agent, benzoporphyrin derivative and new photoimmunoconjugate. Surg Oncol 2:187–196

    Article  CAS  PubMed  Google Scholar 

  41. Kameyama N, Matsuda S, Itano O et al (2011) Photodynamic therapy using an anti-EGF receptor antibody complexed with verteporfin nanoparticles: a proof of concept study. Cancer Biother Radiopharm 26:697–704

    Article  CAS  PubMed  Google Scholar 

  42. Master A, Malamas A, Solanki R et al (2013) A cell-targeted photodynamic nanomedicine strategy for head and neck cancers. Mol Pharm 10:1988–1997

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Christopoulos A, Ahn SM, Klein JD, Kim S (2011) Biology of vascular endothelial growth factor and its receptors in head and neck cancer: beyond angiogenesis. Head Neck 33:1220–1229

    Article  PubMed  Google Scholar 

  44. Dabkeviciene D, Sasnauskiene A, Leman E et al (2012) mTHPC-mediated photodynamic treatment up-regulates the cytokines VEGF and IL-1alpha. Photochem Photobiol 88:432–439

    Article  CAS  PubMed  Google Scholar 

  45. Solban N, Selbo PK, Sinha AK et al (2006) Mechanistic investigation and implications of photodynamic therapy induction of vascular endothelial growth factor in prostate cancer. Cancer Res 66:5633–5640

    Article  CAS  PubMed  Google Scholar 

  46. Bhuvaneswari R, Yuen GY, Chee SK, Olivo M (2011) Antiangiogenesis agents avastin and erbitux enhance the efficacy of photodynamic therapy in a murine bladder tumor model. Lasers Surg Med 43:651–662

    Article  PubMed  Google Scholar 

  47. Ferrario A, Gomer CJ (2006) Avastin enhances photodynamic therapy treatment of Kaposi's sarcoma in a mouse tumor model. J Environ Pathol Toxicol Oncol 25:251–259

    Article  CAS  PubMed  Google Scholar 

  48. Uehara M, Ikeda H, Nonaka M et al (2011) Predictive factor for photodynamic therapy effects on oral squamous cell carcinoma and oral epithelial dysplasia. Arch Oral Biol 56:1366–1372

    Article  CAS  PubMed  Google Scholar 

  49. Zheng G, Chen J, Stefflova K et al (2007) Photodynamic molecular beacon as an activatable photosensitizer based on protease-controlled singlet oxygen quenching and activation. Proc Natl Acad Sci U S A 104:8989–8994

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Rai P, Mallidi S, Zheng X et al (2010) Development and applications of photo-triggered theranostic agents. Adv Drug Deliv Rev 62:1094–1124

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Reddy GR, Bhojani MS, McConville P et al (2006) Vascular targeted nanoparticles for imaging and treatment of brain tumors. Clin Cancer Res 12:6677–6686

    Article  CAS  PubMed  Google Scholar 

  52. Li Z, Wang C, Cheng L et al (2013) PEG-functionalized iron oxide nanoclusters loaded with chlorin e6 for targeted, NIR light induced, photodynamic therapy. Biomaterials 34:9160–9170

    Article  CAS  PubMed  Google Scholar 

  53. Duncan R, Gaspar R (2011) Nanomedicine(s) under the microscope. Mol Pharm 8:2101–2141

    Article  CAS  PubMed  Google Scholar 

  54. Senge MO, Brandt JC (2011) Temoporfin (Foscan(R), 5,10,15,20-tetra(m-hydroxyphenyl)chlorin)—a second-generation photosensitizer. Photochem Photobiol 87:1240–1296

    Article  CAS  PubMed  Google Scholar 

  55. Rigual NR, Shafirstein G, Frustino J et al (2013) Adjuvant intraoperative photodynamic therapy in head and neck cancer. JAMA Otolaryngol Head Neck Surg 139:706–711

    Article  PubMed Central  PubMed  Google Scholar 

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Correspondence to Sophie Marchal.

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Marchal, S., Dolivet, G., Lassalle, HP. et al. Targeted photodynamic therapy in head and neck squamous cell carcinoma: heading into the future. Lasers Med Sci 30, 2381–2387 (2015). https://doi.org/10.1007/s10103-014-1703-4

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  • DOI: https://doi.org/10.1007/s10103-014-1703-4

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