Comparative Analysis of Tetra(2-naphthyl)tetracyano-porphyrazine and Its Iron Complex as Photosensitizers for Anticancer Photodynamic Therapy.

Photodynamic therapy (PDT) is a rapidly developing modality of primary and adjuvant anticancer treatment. The main trends today are the search for new effective photodynamic agents and the creation of targeted delivery systems with the function of controlling the release of the agent in the tumor. Recently, the new group of cyanoarylporphyrazine dyes was reported, which combine the properties of photosensitizers and sensors of the local microenvironment. Such unique characteristics allow the release of the photosensitizer from the transport carrier to be assessed in real time in vivo. The aim of the present work was to compare the photophysical and photobiological properties of tetra(2-naphthyl)tetracyanoporphyrazine and its newly synthesized Fe(II) complex. We have shown that the chelation of the Fe(II) cation with the porphyrazine macrocycle leads to a decrease in molar extinction and an increase in the quantum yield of fluorescence and photostability. We demonstrate that the iron cation significantly affects the rate of dye accumulation in cells, the dark toxicity and photodynamic activity, and the direction of the changes depends on the particular cell line. However, in all the cases, the photodynamic index of a metal complex was higher than that of a metal-free base. In general, both of the compounds were found to be very promising for PDT, including for the use with transport delivery systems, and can be recommended for further in vivo studies.

Ferroptosis and Photodynamic Therapy Synergism: Enhancing Anticancer Treatment.

Photodynamic therapy (PDT) is widely used in cancer treatment; however, several challenges compromise its efficiency. We propose a synergistic action between PDT and ferroptotic cell death. PDT acts as a source of reactive oxygen species for the Fenton reaction, which may reinforce ferroptosis induction and increase PDT efficacy in anticancer therapy.

Preclinical Study of Biofunctional Polymer-Coated Upconversion Nanoparticles.

Upconversion nanoparticles (UCNPs) are new-generation photoluminescent nanomaterials gaining considerable recognition in the life sciences due to their unique optical properties that allow high-contrast imaging in cells and tissues. Upconversion nanoparticle applications in optical diagnosis, bioassays, therapeutics, photodynamic therapy, drug delivery, and light-controlled release of drugs are promising, demanding a comprehensive systematic study of their pharmacological properties. We report on production of biofunctional UCNP-based nanocomplexes suitable for optical microscopy and imaging of HER2-positive cells and tumors, as well as on the comprehensive evaluation of their pharmacokinetics, pharmacodynamics, and toxicological properties using cells and laboratory animals. The nanocomplexes represent a UCNP core/shell structure of the NaYF4:Yb, Er, Tm/NaYF4 composition coated with an amphiphilic alternating copolymer of maleic anhydride with 1-octadecene (PMAO) and conjugated to the Designed Ankyrin Repeat Protein (DARPin 9_29) with high affinity to the HER2 receptor. We demonstrated the specific binding of UCNP-PMAO-DARPin to HER2-positive cancer cells in cultures and xenograft animal models allowing the tumor visualization for at least 24 h. An exhaustive study of the general and specific toxicity of UCNP-PMAO-DARPin including the evaluation of their allergenic, immunotoxic, and reprotoxic properties was carried out. The obtained experimental body of evidence leads to a conclusion that UCNP-PMAO and UCNP-PMAO-DARPin are functional, noncytotoxic, biocompatible, and safe for imaging applications in cells, small animals, and prospective clinical applications of image-guided surgery.

Low-level laser therapy as a modifier of erythrocytes morphokinetic parameters in hyperadrenalinemia.

Low-level laser therapy (LLLT) is widely used in clinical practice for treatment of various pathologies. It is assumed that LLLT impact on microcirculation is among the mechanisms underlying its therapeutic effect. The microcirculation disorder is observed in the pathogenesis of any inflammatory process and is significantly influenced by red blood cells (RBCs). On this point, studying the RBCs morphology under the influence of LLLT on alterated organism is of scientific interest and practical importance. The aim of the present study was to analyze the LLLT effect on morphokinetic parameters of RBCs in hyperadrenalinemia. The LLLT effect was analyzed on rats intraperitoneally injected with adrenaline hydrochloride solution (0.1 mg/kg). As the comparison groups, the effects of LLLT, adrenaline, or saline injection as well as the parameters of intact animals were studied. LLLT was applied on the occipital region of rats for 10 min. The light irradiation with pulse frequency 415 Hz at 890 nm wavelength and average power density in the plane of the output window at 193 µW/cm2 was used. The dynamics of morphological characteristics of RBCs was studied by phase interference microscopy; the RBC electrophoretic mobility was tested by microelectrophoresis technique; photometric analyses of the RBCs amount, hemoglobin content, and osmotic fragility were performed. The adrenaline injection resulted in a significant increase in the amount of RBC pathological forms and a decrease in discocytes and normocytes by more than 50%. An increase in the optical density of RBC phase portraits, a decline in osmotic resistance, and electronegativity of RBC membranes and a reduction of their number in peripheral blood were also registered. The revealed effects persisted for 1 week after the adrenaline administration. LLLT did not significantly impact on the RBC parameters 1 h after adrenaline injection. However, a day later, LLLT reduced the severity of the adrenaline effect on RBSs, which was manifested in a decreased amount of the pathological forms of RBCs, restored RBC phase portraits, higher electrophoretic mobility and osmotic resistance, and RBSs amount in peripheral blood restored up to the level of intact animals. We suppose that the mechanism of LLLT action is realized both at cellular level through the laser radiation effect on RBC membranes, and at systemic level through the activation of stress-realizing systems of the organism with subsequent limitation of inflammatory response.