Photophysical Characterization and in Vitro Phototoxicity Evaluation of 5,10,15,20-Tetra(quinolin-2-yl)porphyrin as a Potential Sensitizer for Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) is a selective and minimally invasive therapeutic approach, involving the combination of a light-sensitive compound, called a photosensitizer (PS), visible light and molecular oxygen. The interaction of these per se harmless agents results in the production of reactive species. This triggers a series of cellular events that culminate in the selective destruction of cancer cells, inside which the photosensitizer preferentially accumulates. The search for ideal PDT photosensitizers has been a very active field of research, with a special focus on porphyrins and porphyrin-related macrocycle molecules. The present study describes the photophysical characterization and in vitro phototoxicity evaluation of 5,10,15,20-tetra(quinolin-2-yl)porphyrin (2-TQP) as a potential PDT photosensitizer. Molar absorption coefficients were determined from the corresponding absorption spectrum, the fluorescence quantum yield was calculated using 5,10,15,20-tetraphenylporphyrin (TPP) as a standard and the quantum yield of singlet oxygen generation was determined by direct phosphorescence measurements. Toxicity evaluations (in the presence and absence of irradiation) were performed against HT29 colorectal adenocarcinoma cancer cells. The results from this preliminary study show that the hydrophobic 2-TQP fulfills several critical requirements for a good PDT photosensitizer, namely a high quantum yield of singlet oxygen generation (Φ∆ 0.62), absence of dark toxicity and significant in vitro phototoxicity for concentrations in the micromolar range.

An updated overview on the development of new photosensitizers for anticancer photodynamic therapy

“…Another new porphyrin derivative 3 bearing ethylenediaminetetraacetic acid showed intense in vitro phototoxicity on HepG2 and BGC823 cell lines, and further inhibited the growth of BGC823 tumors in nude mice 74 , Mechanism studies indicated that 3 can induce cell death via the mitochondrial apoptotic pathway mainly triggered by lysosomal photodamage. Costa et al 76 recently reported a hydrophobic porphyrin derivative 4 bearing four isoquinoline moieties, which showed a high quantum yield of 1 O 2 generation, the absence of toxicity in the dark, and significant in vitro phototoxicity against HT29 cells with an IC 50 in the micromolar range.…”

Chemical approaches for the enhancement of porphyrin skeleton-based photodynamic therapy

“…Derivative 22 ( Figure 6) attached to a quinoline group showed various pharmaceutical activities, including anti-tumour activity, and meets several essential requirements of an ideal PS; for example, it produced 1 O 2 efficiently (U D ¼ 0.62) in tetrahydrofuran. The calculated value was above the range reported for most PSs employed in PDT 48,49 . Benzothiophene-containing porphyrin derivatives were found to selectively accumulate in the mitochondria and nucleus of MCF-7 cells.…”

Photodynamic Therapy Activity of New Porphyrin-Xylan-Coated Silica Nanoparticles in Human Colorectal Cancer

“…Some authors have shown that tetraphenylporphyrin (TPP) derivatives triggered PDT-induced apoptosis. Costa et al reported that 5,10,15,20-Tetra (quinolin-2-yl) porphyrin (2-TQP) decreased cell viability after PDT in HT-29 CRC cells [52]. Baldea et al demonstrated the meso-5,10,15,20-tetrakis (4-hydroxyphenyl) porphyrin (THOPP) induced apoptosis through caspase activation after PDT [53].…”