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

Lilla Pethő, József Murányi, Kinga Pénzes, Bianka Gurbi, Diána Brauswetter, Gábor Halmos, Gabriella Csík, Gábor Mező

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
JournalInternational journal of molecular sciences
Volume20
Issue number20
DOIs
Publication statusPublished - Oct 11 2019

Fingerprint

LHRH Receptors
Photodynamic therapy
hormones
Photochemotherapy
releasing
Head and Neck Neoplasms
therapy
cancer
Gonadotropin-Releasing Hormone
Cells
Peptides
peptides
Photosensitizing Agents
Drug delivery
Prostatic Neoplasms
Cell Survival
Photosensitizers
Protein Isoforms
prognosis
mortality

Keywords

  • conjugate
  • GnRH
  • GnRH-R
  • head and neck cancer
  • photodynamic therapy
  • protoporphyrin
  • targeted drug delivery

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Suitability of GnRH Receptors for Targeted Photodynamic Therapy in Head and Neck Cancers. / Pethő, Lilla; Murányi, József; Pénzes, Kinga; Gurbi, Bianka; Brauswetter, Diána; Halmos, Gábor; Csík, Gabriella; Mező, Gábor.

In: International journal of molecular sciences, Vol. 20, No. 20, 11.10.2019.

Research output: Contribution to journalArticle

Pethő, Lilla ; Murányi, József ; Pénzes, Kinga ; Gurbi, Bianka ; Brauswetter, Diána ; Halmos, Gábor ; Csík, Gabriella ; Mező, Gábor. / Suitability of GnRH Receptors for Targeted Photodynamic Therapy in Head and Neck Cancers. In: International journal of molecular sciences. 2019 ; Vol. 20, No. 20.
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