The ability for noninvasive visualization of functional changes of a tumor's oxygenation and circulatory system offers new advantages for prognosis and monitoring of the treatment efficacy. The results of breast cancer oxygen state study under chemotherapy action obtained by diffuse optical spectroscopy (DOS) in combination with Doppler ultrasonic imaging are presented. Complex use of optical and ultrasound methods gives complementary information about the size of the tumor node, peculiarities of its vascular bed, rate of its blood flow as well as oxygenation, and provide a picture of the tumor response to treatment. Comparison with tumor pathologic response allowed to identify differences in the changes of these parameters depending on the degree of pathological tumor response to chemotherapy. It was demonstrated that fourth and fifth degrees of therapeutic pathomorphism may be predicted by the increase of oxygen saturation level after the first cycle of chemotherapy. If the reduction or absence of the oxygen saturation dynamics is observed, first or second degree of pathological tumor response can be expected. Additional ultrasound investigation of the tumors may be useful for observation of the dynamics of tumor blood flow thereby for understanding the reasons of induced chemotherapy oxygenation changes. The proposed approach based on DOS and ultrasonography may be applied for monitoring of breast tumors under therapy and prediction of their sensitivity.

The unique cyanoporphyrazine pigment with four bulky phenanthrenyl peripheral substituents has been prepared. It demonstrates the noticeable shift of Q-band to longer wavelengths due to phenanthryl aromatic system extension. The compound showed very strong predominance of photoinduced cytotoxicity over cytotoxicity in the dark. The presented results indicate the enhancement of photodynamic properties of porphyrazine containing polycyclic aryl substituents in peripheral framing. It is confirmed that the chemical design of the peripheral aryl groups is an efficient toolkit for a fine tuning of photodynamic properties. Furthermore, we have shown that in spite of the presence of bulky substituents new cyano-aryl porphyrazine demonstrates the properties of fluorescent molecular rotors, i.e. the segmental intramolecular mobility in environment of low viscosity. Previously on the example of related cyano-aryl porphyrazines combining the properties of fluorescent molecular rotors and photosensitizers we have demonstrated high potential of these compounds as the sensors of local viscosity and rigidity of biological submicrometer environment within a living cell. So, in respect to PDT it can be a significant expansion of photosensitizer functionality as a potential agent of optical theranostics.

Photodynamic therapy is one of the most promising methods for the treatment of oncological, inflammatory and degenerative diseases of the skin. This technique is based on light irradiation of a photosensitizer that has been injected into the patient's body prior to the procedure, with determination of the efficacy of treatment requiring proper assessment of the drug concentration in the tissue lesion and the extent of sensitizer photobleaching during irradiation. We have developed a compact and low cost device based on a fluorescence imaging for localizing the tumor in the patient's body, tracking the position of the tissue lesion during involuntary movements of the patient, estimating accumulation of the sensitizer in the tumor relative to the surrounding tissues and monitoring photobleaching of the sensitizer during laser irradiation. The system that has been created is compatible with any therapeutic laser and includes a single CCD camera and two LEDs, one in the excitation band and the other in the emission band of the 'Photoditazin' sensitizer. In this letter we also present the test results of the device in model experiments and in preliminary clinical trials. The results obtained clearly show the efficacy of the system for monitoring sensitizer photobleaching during photodynamic therapy.

Despite the significant relevance of photodynamic therapy (PDT) as an efficient strategy for primary and adjuvant anticancer treatment, several challenges compromise its efficiency. In order to develop an “ideal photosensitizer” and the requirements applied to photosensitizers for PDT, there is still a need for new photodynamic agents with improved photophysical and photobiological properties. In this study, we performed a detailed characterization of two tetracyanotetra(aryl)porphyrazine dyes with 4-biphenyl (pz II) and 4-diethylaminophenyl (pz IV) groups in the periphery of the porphyrazine macrocycle. Photophysical properties, namely, fluorescence quantum yield and lifetime of both photosensitizers, demonstrate extremely high dependence on the viscosity of the environment, which enables them to be used as viscosity sensors. PzII and pz IV easily enter cancer cells and efficiently induce cell death under light irradiation. Using fluorescence lifetime imaging microscopy, we demonstrated the possibility of assessing local intracellular viscosity and visualizing viscosity changes driven by PDT treatment with the compounds. Thus, pz II and pz IV combine the features of potent photodynamic agents and viscosity sensors. These data suggest that the unique properties of the compounds provide a tool for PDT dosimetry and tailoring the PDT treatment regimen to the individual characteristics of each patient.

Increase of the efficiency of photodynamic therapy (PDT) requires the development of advanced protocols employing both novel photosensitizer (PS) carriers and aids for online monitoring. Nanoconstructs may be comprised of a photosensitizer, chemotherapy drugs, or inhibitors of molecular pathways that support cancer growth. In this paper, we analyze the efficiency of a bimodal approach involving fluorescence and optoacoustic imaging in monitoring drug distribution and photobleaching. The study evaluates typical sensitivities of these techniques to the presence of the two key moieties of a nanoconstruct: benzoporphyrin derivatives (BPD) serving as a PS, and IRDye800 acting as a contrast agent. Both imaging modalities employ dual-wavelength probing at the wavelengths corresponding to absorption peaks of BPD and IRDye800, which enables their separate detection. In an experiment on a tissue-mimicking phantom with inclusions containing separate BPD and IRDye800 solutions, fluorescence imaging demonstrated higher contrast as compared to optoacoustic imaging for both components, though strong light scattering in the surrounding media restricted accurate localization of the markers. It was also sensitive to photobleaching, which is a measure of PDT efficiency. Optoacoustic imaging demonstrated sufficient sensitivity to both components, though less than that of fluorescence imaging, however, it enabled depth-resolved detection of an absorber and estimation of its relative content. Employment of the bimodal approach in monitoring of PS photobleaching adds to its potential in intraprocedural PDT monitoring.