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Open AccessArticle

Suitability of GnRH Receptors for Targeted Photodynamic Therapy in Head and Neck Cancers

1
MTA-ELTE Research Group of Peptide Chemistry, 1117 Budapest, Hungary
2
MTA-SE Pathobiochemistry Research Group, 1094 Budapest, Hungary
3
Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, 4032 Debrecen, Hungary
4
SE Department of Biophysics and Radiation Biology, 1094 Budapest, Hungary
5
Department of Organic Chemistry, Faculty of Science, Institute of Chemistry, ELTE Eötvös Loránd University, 1117 Budapest, Hungary
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(20), 5027; https://doi.org/10.3390/ijms20205027
Received: 26 July 2019 / Revised: 2 October 2019 / Accepted: 8 October 2019 / Published: 11 October 2019
(This article belongs to the Special Issue The Role of Gonadotropin-Releasing Hormone Receptor in Human Diseases)
Head and neck squamous cell carcinomas (HNSCC) have a high mortality rate, although several potential therapeutic targets have already been identified. Gonadotropin-releasing hormone receptor (GnRH-R) expression is less studied in head and neck cancers, hence, we investigated the therapeutic relevance of GnRH-R targeting in HNSCC patients. Our results indicate that half of the patient-derived samples showed high GnRH-R expression, which was associated with worse prognosis, making this receptor a promising target for GnRH-based drug delivery. Photodynamic therapy is a clinically approved treatment for HNSCC, and the efficacy and selectivity may be enhanced by the covalent conjugation of the photosensitizer to a GnRH-R targeting peptide. Several native ligands, gonadotropin-releasing hormone (GnRH) isoforms, are known to target GnRH-R effectively. Therefore, different 4Lys(Bu) modified GnRH analogs were designed and conjugated to protoporphyrin IX. The receptor binding potency of the novel conjugates was measured on human pituitary and human prostate cancer cells, indicating only slightly lower GnRH-R affinity than the peptides. The in vitro cell viability inhibition was tested on Detroit-562 human pharyngeal carcinoma cells that express GnRH-R in high levels, and the results showed that all conjugates were more effective than the free protoporphyrin IX. View Full-Text
Keywords: GnRH-R; GnRH; protoporphyrin; targeted drug delivery; conjugate; photodynamic therapy; head and neck cancer GnRH-R; GnRH; protoporphyrin; targeted drug delivery; conjugate; photodynamic therapy; head and neck cancer
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Pethő, L.; Murányi, J.; Pénzes, K.; Gurbi, B.; Brauswetter, D.; Halmos, G.; Csík, G.; Mező, G. Suitability of GnRH Receptors for Targeted Photodynamic Therapy in Head and Neck Cancers. Int. J. Mol. Sci. 2019, 20, 5027.

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