Tuning Photodynamic Properties of BODIPY Dyes, Porphyrins' Little Sisters.

Wojciech Krzemien,Jaroslaw Piskorz,Monika Rohlickova,Miloslav Machacek,Petr Zimcik,Veronika Novakova

doi:10.3390/molecules26144194

Abstract

The photodynamic properties of a series of non-halogenated, dibrominated and diiodinated BODIPYs with a phthalimido or amino end modification on the phenoxypentyl and phenoxyoctyl linker in the meso position were investigated. Halogen substitution substantially increased the singlet oxygen production based on the heavy atom effect. This increase was accompanied by a higher photodynamic activity against skin melanoma cancer cells SK-MEL-28, with the best compound reaching an EC50 = 0.052 ± 0.01 µM upon light activation. The dark toxicity (toxicity without light activation) of all studied dyes was not detected up to the solubility limit in cell culture medium (10 µM). All studied BODIPY derivatives were predominantly found in adiposomes (lipid droplets) with further lower signals colocalized in either endolysosomal vesicles or the endoplasmic reticulum. A detailed investigation of cell death indicated that the compounds act primarily through the induction of apoptosis. In conclusion, halogenation in the 2,6 position of BODIPY dyes is crucial for the efficient photodynamic activity of these photosensitizers.

Highlights

IntroductionPDT is a minimally invasive modality for the treatment of cancer, age-related macular degeneration, therapy of acne, or for killing infectious microorganisms [7]
Two series of the BODIPY dyes which varied in the length of the alkyl linker beTwo series of the dyes which varied in the group, length of linker substituent between theBODIPY
While strong singlet oxygen production (Φ∆ ~ 0.76) and weak fluorescence (Φ∆ ~ 0.03) was observed for diiodinated compounds, data completely the reverse were determined for 2,6

Summary

Introduction

PDT is a minimally invasive modality for the treatment of cancer, age-related macular degeneration, therapy of acne, or for killing infectious microorganisms [7]. It involves three harmless components—a photosensitizer (PS), visible light, and molecular oxygen. PS is activated by light absorption to a singlet excited state and undergoes intersystem crossing to the triplet state. From this state, it can transfer the obtained energy to a ground state triplet oxygen, forming a highly reactive singlet oxygen [8], which is responsible for cell death. Several other porphyrin analogues have been clinically approved by the Food and Drug Administration (e.g., verteporfin in 2000) or by the European Medicine Agency

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