Highly Phototoxic Transplatin‐Modified Distyryl‐BODIPY Photosensitizers for Photodynamic Therapy

Abstract

We report the synthesis of the first transplatin‐BODIPY conjugates for application in photodynamic therapy (PDT). The distyryl BODIPYs containing two iodine atoms were designed to absorb in the red region, easily undergo intersystem crossing for efficient singlet oxygen generation, and additionally offer the possibility for coordination with mono‐activated transplatin. We were able to demonstrate that coordination of the BODIPYs with a mono‐activated transplatin increases the phototoxic index of the photosensitizers significantly, giving rise to highly phototoxic distyryl BODIPY derivatives, of which one was shown to have the highest ever reported phototoxic index against any cell line. Furthermore, the photophysical mechanism of singlet oxygen generation in distyryl BODIPYs undergoing intramolecular charge transfer was studied experimentally and using time‐dependent density functional theory.

Chlorin Endogenous to the North Pacific Brittle Star Ophiura sarsii for Photodynamic Therapy Applications in Breast Cancer and Glioblastoma Models

“…Cell growth in the subsequent 72 h was assessed with the MTT assay (see Methods). Resulting data ( Figure 2 B,C) show striking phototoxicity of ETPA, with the sub-micromolar to low-micromolar IC 50 s and impressive phototoxic indices (PI, measured as IC 50 in the dark/IC 50 in the light [ 17 ], Figure 2 C), arguing for the strong potential of this natural chlorin in PDT applications. Notably, dark phototoxicity for the glioma C6 cells was not achieved at the highest concentrations of ETPA tested ( Figure 2 C and Supplementary Figure S4 ).…”

“… ( A ) Absorbance spectra of the chlorin compound isolated from the butanol fraction of the EtOH extract from control (red) and fasted (black) O. sarsii reveal absorbance peaks typical for chlorins, identical between the two preparations; ( B ) cell survival (MTT test) to evaluate the strong phototoxicity of ETPA after red-light irradiation. Data are given as mean ± SEM, n = 8 (3 for HEK-293 cells); ( C ) ETPA phototoxicity IC 50 and the phototoxicity index (PI, calculated as IC 50 in the dark/IC 50 in the light [ 17 ]). Cell survival data in the dark are taken from [ 10 ] (breast cancer cell lines) or measured separately (C6 and HEK-293 cells, see Supplementary Figure S4 ).…”

Photochemical Properties and Stability of BODIPY Dyes

“…Additionally, the absorption and emission range of BODIPY can be rationally modified by proper substitution at 2, 6 and other positions in the molecular core. Only recently, BODIPYs were successfully applied for bacteria photoinactivation [20][21][22] and as photosensitizers in PDT, modified with a heavy atom (iodine, bromine, metal cation) for efficient triplet state population [4,7,[23][24][25][26][27][28][29]. All of these works appeared in recent years, thus pointing out the possible practical applications of BODIPY in therapy and the need for their advanced developments.…”

One-Pot Strategy for Symmetrical and Unsymmetrical BOIMPY Fluorophores

“…Their advantages include their convenient synthetic preparations, chemical stability, and broad modification possibilities as well as their beneficial photophysical properties, such as high fluorescence quantum yields and sharp emission peaks . These properties lead to numerous applications, e.g., fluorescence labeling and bioimaging, photodynamic therapy, chemical sensors, tunable laser dyes, OLEDs, solar panels, and as viable compounds for fundamental photophysical research . Lately, a popular direction for tuning the photoelectronic properties of BODIPYs involves various dimerization and oligomerization approaches, such as ethylene-bridged J-aggregate-promoting superfluorophores and fully conjugated benzene-fused BODIPYs from simple BODIPY precursors.…”