Lead Structures for Applications in Photodynamic Therapy. 6. Temoporfin Anti-Inflammatory Conjugates to Target the Tumor Microenvironment for In Vitro PDT

Luke Rogers; Natalia N Sergeeva; Edyta Paszko; Gisela M F Vaz; Mathias O Senge

doi:10.1371/journal.pone.0125372

Lead Structures for Applications in Photodynamic Therapy. 6. Temoporfin Anti-Inflammatory Conjugates to Target the Tumor Microenvironment for In Vitro PDT

PLoS One. 2015 May 19;10(5):e0125372. doi: 10.1371/journal.pone.0125372. eCollection 2015.

Authors

Luke Rogers¹, Natalia N Sergeeva², Edyta Paszko², Gisela M F Vaz², Mathias O Senge³

Affiliations

¹ School of Chemistry, SFI Tetrapyrrole Laboratory, Trinity Biomedical Sciences Institute, 152-160 Pearse Street, Trinity College Dublin, The University of Dublin, Dublin, 2, Ireland.
² Medicinal Chemistry, Institute of Molecular Medicine, Trinity Centre for Health Sciences, Trinity College Dublin, St. James's Hospital, Dublin, 8, Ireland.
³ School of Chemistry, SFI Tetrapyrrole Laboratory, Trinity Biomedical Sciences Institute, 152-160 Pearse Street, Trinity College Dublin, The University of Dublin, Dublin, 2, Ireland; Medicinal Chemistry, Institute of Molecular Medicine, Trinity Centre for Health Sciences, Trinity College Dublin, St. James's Hospital, Dublin, 8, Ireland.

Abstract

Due to the ongoing development of clinical photodynamic therapy (PDT), the search continues for optimized photosensitizers that can overcome some of the side effects associated with this type of treatment modality. The main protagonists being: post-treatment photosensitivity, due to only limited cellular selectivity and post-treatment tumor regrowth, due to the up-regulation of pro-inflammatory agents within the tumor microenvironment. A photosensitizer that could overcome one or both of these drawbacks would be highly attractive to those engaged in clinical PDT. Certain non-steroidal anti-inflammatory drugs (NSAIDs) when used in combination with PDT have shown to increase the cytotoxicity of the treatment modality by targeting the tumor microenvironment. Temoporfin (m-THPC), the gold standard chlorin-based photosensitizer (PS) since its discovery in the 1980's, has successfully been conjugated to non-steroidal anti-inflammatory compounds, in an attempt to address the issue of post-treatment tumor regrowth. Using a modified Steglich esterification reaction, a library of "iPorphyrins" was successfully synthesized and evaluated for their PDT efficacy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Inflammatory Agents / therapeutic use*
Humans
In Vitro Techniques
Mesoporphyrins / therapeutic use*
Neoplasms / drug therapy*
Neoplasms / pathology
Photochemotherapy*
Photosensitizing Agents / therapeutic use*
Tumor Microenvironment*

Substances

Anti-Inflammatory Agents
Mesoporphyrins
Photosensitizing Agents
temoporfin

Grants and funding

MOS: Science Foundation Ireland (SFI, 12/TIDA/B2381 and IvP 13/IA/1894). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.