Trifluoromethyl Boron Dipyrromethene Derivatives as Potential Photosensitizers for Photodynamic Therapy.

In this study, two novel boron dipyrromethene-based photosensitizers (BDP3 and BDP6) substituted with three or six trifluoromethyl groups have been synthesized and characterized with various spectroscopic methods, and their photo-physical, photo-chemical, and photo-biological properties have also been explored. The two photosensitizers are highly soluble and remain nonaggregated in N,N-dimethylformamide as shown by the intense and sharp Q-band absorption. Under red light irradiation (λ = 660 nm, 1.5 J/cm²), both photosensitizers show high and comparable cytotoxicity towards HepG2 human hepatocarcinoma and HeLa human cervical carcinoma cells with IC50 values of 0.42-0.49 µM. The high photocytotoxicity of BDP3 and BDP6 can be due to their high cellular uptake and low aggregation tendency in biological media, which result in a high efficiency to generate reactive oxygen species inside the cells. Confocal laser fluorescence microscopic studies indicate that they have superior selective affinities to the mitochondria and lysosomes of HepG2 and HeLa cells. The results show that these two trifluoromethyl boron dipyrromethene derivatives are potential anticancer agents for photodynamic therapy.

TRASER: acute phase vascular and follicular changes.

BACKGROUND AND OBJECTIVES: A TRASER (Total Reflection Amplification of Spontaneous Emission of Radiation) is a novel device that utilizes the energy from a flashlamp to induce the spontaneous emission of photons from a fluorescent medium. This study was designed to observe clinical and histological changes of skin treated with two different fluorescent media selected for their peak emissions tuned for vascular and hair follicle targets. STUDY DESIGN/MATERIALS AND METHODS: A purpuric clinical response for the vascular target was assessed with a TRASER using the fluorescent medium Pyrromethene 556 producing a narrow spectrum peaking at 544 nm. Using a 12 mm spot and pulse duration of 1 ms, treatment pulses with fluences of 6.0-9.5 J/cm2 were given along the forearm of subject with photo type II skin. Follicular structures were targeted with the dye cell switched to Sulforhodamine 640 Chloride, producing a narrow peak at 654 nm. Using a 12 mm spot, single 20 ms pulses with fluencies from 14.0 to 20.0 J/cm2 were delivered with 5 °C contact cooling to the shaved chest of a subject with photo type II skin with brown hair. Clinical observations were photographed and assessed by two physicians. A 4 mm punch skin biopsy was taken at approximately 60 and 30 minutes respectively for both the vascular and hair regions. The paraffin embedded H&E stained vertical sections were analyzed by a dermatopathologist. RESULTS: A characteristic threshold purpuric response was noted at 7.2 J/cm2 . The histological changes consistently showed intravascular thrombosis of the small sub-dermal plexus of capillaries down to larger vessels approaching the subcutaneous fat. There were no extravasated red blood cells. Clinical hair follicle target changes of perifollicular edema and transient erythema, similar to those described with standard hair removal lasers, were noted. Histologically these were shown to be limited to the target structures. CONCLUSION: This is the first demonstration of clinical and histological acute phase changes associated with use of a TRASER with wavelengths optimized for vascular and follicular targets. The findings of this observational study support the notion that the TRASER can be used as an effective vascular and hair removal device.

In vitro and in vivo photocytotoxicity of boron dipyrromethene derivatives for photodynamic therapy.

To understand the effects of substitution patterns on photosensitizing the ability of boron dipyrromethene (BODIPY), two structural variations that either investigate the effectiveness of various iodinated derivatives to maximize the "heavy atom effect" or focus on the effect of extended conjugation at the 4-pyrrolic position to red-shift their activation wavelengths were investigated. Compounds with conjugation at the 4-pyrrolic position were less photocytotoxic than the parent unconjugated compound, while those with an iodinated BODIPY core presented better photocytotoxicity than compounds with iodoaryl groups at the meso-positions. The potency of the derivatives generally correlated well with their singlet oxygen generation level. Further studies of compound 5 on HSC-2 cells showed almost exclusive localization to mitochondria, induction of G(2)/M-phase cell cycle block, and onset of apoptosis. Compound 5 also extensively occluded the vasculature of the chick chorioallantoic membrane. Iodinated BODIPY structures such as compound 5 may have potential as new photodynamic therapy agents for cancer.