The Dark Side: Photosensitizer Prodrugs

Abstract

Photodynamic therapy (PDT) and photodiagnosis (PD) are essential approaches in the field of biophotonics. Ideally, both modalities require the selective sensitization of the targeted disease in order to avoid undesired phenomena such as the destruction of healthy tissue, skin photosensitization, or mistaken diagnosis. To a large extent, the occurrence of these incidents can be attributed to “background” accumulation in non-target tissue. Therefore, an ideal photoactive compound should be optically silent in the absence of disease, but bright in its presence. Such requirements can be fulfilled using innovative prodrug strategies targeting disease-associated alterations. Here we will summarize the elaboration, characterization, and evaluation of approaches using polymeric photosensitizer prodrugs, nanoparticles, micelles, and porphysomes. Finally, we will discuss the use of 5-aminolevulinc acid and its derivatives that are selectively transformed in neoplastic cells into photoactive protoporphyrin IX.

Photophysical Properties of Protoporphyrin IX, Pyropheophorbide-a, and Photofrin® in Different Conditions

“…Illumination of the PS induces the production of the triplet excited state 3 PS* which is able to transfer protons, electrons, or energy, leading to the formation of reactive oxygen species (ROS). ROS cause apoptosis or necrosis of tumor cells by photochemical oxidation [ 1 , 2 , 3 ].…”

Protein-aggregating ability of different protoporphyrin-IX nanostructures is dependent on their oxidation and protein-binding capacity

“…Porphyrin-mediated protein aggregation plays a major role in porphyria-associated tissue damage ( 27 , 39 , 42 ). PP-IX oligomerization causes static quenching of the fluorophore ( 3 , 53 ), leading to dramatically reduced quantum yield and protein aggregation ( Figs. 2 A and 3 ), highlighting the importance of preventing PP-IX aggregation in order to hinder porphyrin-mediated cell damage.…”

“…Porphyrin-mediated protein aggregation plays a major role in porphyria-associated tissue damage (27,39,42). PP-IX oligomerization causes static quenching of the fluorophore (3,53), leading to dramatically reduced quantum yield, and to protein aggregation (Fig. 2A, Fig.…”

Acetylxylan‐pheophorbide‐a nanoparticles designed for tumor‐targeted photodynamic therapy

“…The excited PS transfers its energy to molecular oxygen, generating cytotoxic reactive oxygen species (ROS), especially singlet oxygen ( 1 O 2 ) that can lead to cell death. So only cells that have accumulated PS, located in the irradiation zone and contain molecular oxygen are affected by this treatment 3 . Efficacy of PDT mainly depends on PS photophysical properties.…”