Synthesis and evaluation of 5,15-diaryltetrabenzoporphyrins as photosensitizers for photo-diagnosis and photodynamic activity of tumors.

Photodynamic therapy (PDT) is a well-established treatment modality, typically conducted with single-wavelength irradiation, which may not always be optimal for varying tumor locations and sizes. To address this, photosensitizers with absorption wavelengths ranging from 550 to 760 nm are being explored. Herein, a series of 5,15-diaryltetrabenzoporphyrins (Ar2TBPs) were synthesized. All compounds displayed obvious absorption at 550-700 nm (especially at ∼668 nm), intense fluorescence, efficient generation of singlet oxygen and good photodynamic antitumor effects. Notably, compound I3 (5,15-bis[(4-carboxymethoxy)phenyl]tetrabenzoporphyrin) showed excellent cytotoxicity against Eca-109 cell line upon red light irradiation, with an IC50 value of 0.45 µM, and phototherapeutic index of 25.8. Flow cytometry revealed that I3 could induce distinct cell apoptosis. In vivo studies revealed that compound I3 selectively accumulated at tumor site and exhibited outstanding PDT effect with antitumor activity under single-time administration and light irradiation, and revealed more efficiency than the clinical photosensitizer Verteporfin. These findings underscore the considerable promise of I3 as a robust theranostic agent, offering capabilities in real-time fluorescence imaging and serving as a potent photosensitizer for personalized and precise photodynamic therapy of tumors.

The bromoporphyrins as promising anti-tumor photosensitizers in vitro.

The synthesis of ideal photosensitizers (PSs) is considered to be the most significant bottleneck in photodynamic therapy (PDT). To discover novel PSs with excellent photodynamic anti-tumor activities, a series of novel photosensitizers 5,15-diaryl-10,20-dibromoporphyrins (I1-6) were synthesized by a facile method. Compared with hematoporphyrin monomethyl ether (HMME) as the representative porphyrin-based photosensitizers, it is found that not only the longest absorption wavelength of all compounds was red-shifted to therapeutic window (660 nm) of photodynamic therapy, but also the singlet oxygen quantum yields were significantly increased. Furthermore, all compounds exhibited lower dark toxicity (except I2) and stronger phototoxicity (except I4) against Eca-109 tumor cells than HMME. Among them, I3 possessed the highest singlet oxygen quantum yield (ΦΔ = 0.205), the lower dark toxicity and the strongest phototoxicity (IC50 = 3.5 µM) in vitro. The findings indicated the compounds I3 had the potential to become anti-tumor agents for PDT.

The biological activities of 5,15-diaryl-10,20-dihalogeno porphyrins for photodynamic therapy.

PURPOSE: Esophageal cancer is the most common gastrointestinal tumor and is difficult to be eradicated with conventional treatment. Porphyrin-based photosensitizers (PSs) mediated photodynamic therapy (PDT) could kill tumor cells with less damage to normal cells. As the most widely used porphyrin-based photosensitizer in clinics, Photofrin II has excellent anti-tumor effect. However, it has some disadvantages such as weak absorption at near infrared region, the complexity of components and prolonged skin photosensitivity. Here series novel 5,15-diaryl-10,20-dihalogeno porphyrin derivatives were afforded and evaluated to develop more effective and safer photosensitizers for tumor therapy. METHODS: The photophysical properties and singlet oxygen generation rates of 5,15-diaryl-10,20-dihalogeno porphyrins (I1-6, II1-4) were tested. The cytotoxicity of I1-6 and II1-4 were measured by MTT assay. The pathway of cell death was studied by flow cytometry. In vivo photodynamic efficacy of I3 and II2-4 in Eca-109 tumor-bearing BABL/c nude mice were measured and histopathological analysis were examined. RESULTS: 5,15-Diaryl-10,20-dihalogeno porphyrins I1-6 and II1-4 were synthesized. The longest absorption wavelength of these halogenated porphyrins (λmax = 660 nm) displayed a red shift around 30 nm compared to the unhalogenated porphyrins PS1 (λmax = 630 nm). The singlet oxygen generation rates of I1-6 and II1-4 were significantly higher than PS1 and HMME. All PSs mediated PDT showed obvious cytotoxic effect against Eca-109 cells compared to HMME in vitro and in vivo. Among these PSs, II4 exhibited appropriate absorption in the phototherapeutic window, higher 1O2 generation rate (k = 0.0061 s-1), the strongest phototoxicity (IC50 = 0.4 µM), lower dark toxicity, high generation of intracellular ROS in Eca-109 cells and excellent photodynamic anti-tumor efficacy in vivo. Besides, cell necrosis was induced by compound II4 mediated PDT. CONCLUSION: All new compounds have obvious photodynamic anti-esophageal cancer effects. Among them, the photosensitizer II4 showed excellent efficacy in vitro and in vivo, which has the potential to become a photodynamic anti-tumor drug.

Between-subject correlation of heart rate variability predicts movie preferences.

We introduce a novel and simple method for assessing audiences' emotional responses to audiovisuals (e.g. films). Viewers (N = 21) watched movies and TV commercials from different genres while wearing photoplethysmography (PPG) optic sensors on their wrists. Heart rate variability (HRV) synchrony was observed among the audience. Based on this between-subject synchrony measure, we identified emotionally arousing segments from the materials. New participants (N = 24; N = 16) were then invited to watch these identified segments along with some randomly selected segments as control; they reported that the former was more engaging (effect size w = .67; w = .5). This finding was confirmed in an online study with a larger cohort (N = 300). While some specific effects varied depending on movie genre or gender, HRV-based editing generally performed better than the control. These findings suggest that HRV synchrony can be used as a new tool for audience psychology, and potentially also for automatically creating short trailers out of movies in a principled manner while taking into account the human perspective.

Synthesis and evaluation of novel fluorinated hematoporphyrin ether derivatives for photodynamic therapy.

A photosensitizer with high phototoxicity, suitable amphipathy and low dark toxicity could play a pivotal role in photodynamic therapy (PDT). In this study, a facile and versatile approach was adopted to synthesize a series of novel fluorinated hematoporphyrin ether derivatives (I1-I5 and II1-II4), and the photodynamic activities of these compounds were studied. Compared to hematoporphyrin monomethyl ether (HMME), all PSs showed preferable photodynamic activity against A549 lung tumor cells. The longest visible absorption wavelength of these compounds was approximately 622 nm. Among them, II3 revealed the highest singlet oxygen yield (0.0957 min-1), the strongest phototoxicity (IC50 = 1.24 µM), the lowest dark toxicity in vitro, and exhibited excellent anti-tumor effects in vivo. So compound II3 could act as new drug candidate for photodynamic therapy.

Synthesis and pharmacological evaluation of chlorin derivatives for photodynamic therapy of cholangiocarcinoma.

Photodynamic therapy (PDT) has been developed as a promising therapeutic method in cancer treatment. The discovery of effective photosensitizer, which is the key factor of PDT, is highly desired. This paper reports the synthesis of novel chlorin derivatives, 5,10,15,20-tetraphenyl-[2:3]-[(methoxycarbonyl, carboxy)methano] chlorin I and 5,10,15,20-tetraphenyl-[2:3]- {[methoxycarbonyl, (2-hydroxyethyl)amide]methano}chlorin II. Their structures were characterized with UV-vis, 1HNMR, 13CNMR and HRMS spectroscopies. Photophysical and photochemical experiments results showed that compound I and II had an absorption maximum around 650 nm, with molar extinction coefficients of 1 × 104 M-1 cm-1. They had strong fluorescence emission in 650-660 nm upon excitation with 419-422 nm light. ESR showed that singlet oxygen was produced upon irradiation of compounds with 650 nm light in the presence of molecular oxygen. The photo-bleaching test indicated that the structure of compounds was stable. These new compounds exhibit excellent anti-tumor effects and lower toxicity compared to m-THPC in vitro and in vivo. Compound I and II had high tumor selectivity, which could induced tumor cells shrinkage and necrosis under 650 nm laser irradiation. Flow cytometry revealed that the compounds might mediate PDT effect at late apoptotic phase. These results make these compound I and II promising candidates for future study in photo-diagnosis and photodynamic therapy of cholangiocarcinoma.