One-Photon and Two-Photon Photophysical Properties of Tetrafunctionalized 5,10,15,20-tetrakis(m-hydroxyphenyl)chlorin (Temoporfin) Derivatives as Potential Two-Photon-Induced Photodynamic Therapy Agents

Abstract

Photodynamic therapy (PDT) is a cancer treatment, which exploits a photosensitizing drug and light to produce reactive oxygen species that can cause selective damage to the target tissue. The second-generation photosensitizer 5,10,15,20-tetrakis(m-hydroxyphenyl)chlorin (m-THPC) is a widely used, clinically tested, and commercially available drug with the market formulation known as Foscan. m-THPC was used as a starting point to obtain a library of compounds with improved optical properties. Substitution, esterification and Sonogashira coupling reactions were employed to modify the m-THPC skeleton. Aldehyde and carboxylic acid moieties provided the possibility to enhance the two-photon absorption (TPA) cross-section while being suitable synthetic handles in the design of drug delivery systems. Characterization of their linear photophysical properties (fluorescence quantum yield, fluorescence lifetime and singlet oxygen quantum yield) was followed by the evaluation of their potential use in a non-linear absorption regime. The calculated TPA cross-section values indicate even a 2.6-fold enhancement at the TPA maximum (69.3±10.0 GM), compared to m-THPC (26.7±4.0 GM), which proves that functionalization of the m-THPC core leads to the improvement of the non-linear optical properties. Thus, tetrafunctionalized m-THPC derivatives are promising candidates for application in two-photon induced PDT.