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.
The use of two-photon absorption (TPA) for such applications as microscopy, imaging, and photodynamic therapy (PDT) offers several advantages over the usual one-photon excitation. This creates a need for photosensitizers that exhibit both strong two-photon absorption and the highly efficient generation of reactive oxygen species (ROS), as well as, ideally, bright luminescence. This review focuses on different strategies utilized to improve the TPA properties of various multi-photon absorbing species that have the required photophysical properties. Along with well-known families of photosensitizers, including porphyrins, we also describe other promising organic and organometallic structures and more complex systems involving organic and inorganic nanoparticles. We concentrate on the published studies that provide two-photon absorption cross-section values and the singlet oxygen (or other ROS) and luminescence quantum yields, which are crucial for potential use within PDT and diagnostics. We hope that this review will aid in the design and modification of novel TPA photosensitizers, which can help in exploiting the features of nonlinear absorption processes.
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