Advantages of Long-Wavelength Photosensitizer meso-Tetra(3-pyridyl) Bacteriochlorin in the Therapy of Bulky Tumors.

This research presents a novel synthetic photosensitizer for the photodynamic therapy (PDT) of malignant tumors: meso-tetra(3-pyridyl) bacteriochlorin, which absorbs at 747 nm (in the long-wavelength region of the spectrum) and is stable when stored in the dark. H2Py4BC demonstrates pronounced photoinduced activity in vitro against tumor cells of various geneses (IC50 varies from 21 to 68 nM for HEp2, EJ, S37, CT26, and LLC cultured cells) and in vivo provides pronounced antitumor efficacy in the treatment of mice bearing small or large S37, Colo26, or LLC metastatic tumors, as well as in the treatment of rats bearing RS-1 liver cholangioma. As a result, total regression of primary tumor nodules and cure of 40 to 100% of the animals was proven by the experiment criteria, MRI, and histological analysis. Meso-tetra(3-pyridyl) bacteriochlorin quickly penetrates and accumulates in the tumor tissue and internal organs of mice, and after 24 h, 80% of the dye is excreted from the skin in addition to 87-92% from the liver, kidneys, and spleen.

Development of a Dosage form for a Photoswitchable Local Anesthetic Ethercaine.

The toxicity of local anesthetics is a serious problem, given their widespread use. One of the main causes of the side effects of local anesthetics is their non-selectivity of action in the body. A possible way to increase the selectivity of the action of drugs is to use the photopharmacology approach. Previously, we described the light-controlled local anesthetic ethercaine, the biological effect of which can be controlled using light, thereby increasing its selectivity of action. An important limitation of ethercaine was its low solubility in water, limiting the potential of this compound. In this work, we developed a dosage form of ethercaine, which allowed us to increase its solubility from 0.6% to 2% or more. The resulting 1% solution of ethercaine hydrochloride in 4% Kolliphor ELP had high biological activity on the surface anesthesia model, while demonstrating low acute toxicity in mice with intravenous administration (4-5 times less than that of lidocaine).

Effectiveness of Photodynamic Therapy as Antiseptic Measure for Oral Cavity and Pharynx: A Systematic Review.

BACKGROUND: The complex traditional treatment of inflammation diseases in oral cavity includes the prescription of antibiotic and antiseptic therapy. This systematic review aims to evaluate the effect of photodynamic therapy as a part of management of inflammatory diseases in oral cavity; Methods: The study is presented in accordance with the preferred reporting points for systematic reviews and meta-analyses (PRISMA). This systematic review was conducted using electronic databases such as Medline PubMed, Scopus and the Cochrane Central Register of Controlled Trials. All the studies in this systematic review, were randomized, the risk of bias 2 (ROB 2) were assessed; Results: Considering the inclusion and exclusion criteria, we included 10 randomized clinical trials, published up to 2023 investigating the application of photodynamic therapy as a part of management of inflammatory diseases in oral cavity. The diode laser was used in the oral cavity in the zone of inflammatory process (gingivitis, mucositis, periimplantitis, marginal periodontitis, abscess, periostitis, osteomyelitis etc.) in nine studies or in the zone before surgical procedures in one study; Conclusion: Based on the results of clinical studies, it can be stated that photodynamic therapy shows good results for operations performed in the oral cavity and pharynx.

Advantages of combined photodynamic therapy in the treatment of oncological diseases.

When conducting combined therapy of malignant neoplasms, treatment methods with various mechanisms of antitumor effects are used, while an additive or even synergistic effect can be realized. Combination treatment regimens are aimed at increasing the efficiency and, above all, at the complete eradication of the tumor, which can be achieved either by suppressing the survival mechanisms in PDT-resistant tumor cells or by pre-attenuation of tumor cells so that they become more susceptible to subsequent PDT. Photodynamic therapy is an approved medical technology for the treatment of various malignant neoplasms, and several precancerous and non-cancer diseases. To date, numerous data have been published on the combined use of PDT with traditional and innovative methods of treatment. This review considers research in this area in recent years.

A Novel Photoswitchable Azobenzene-Containing Local Anesthetic Ethercaine with Light-Controlled Biological Activity In Vivo.

Pain is a common symptom that impairs the quality of life for people around the world. Local anesthetics widely used for pain relief have a number of side effects, which makes the development of both new drugs and new ways to control their activity particularly important. Photopharmacology makes it possible to reduce the side effects of an anesthetic and control its biological activity in the body. The purpose of this work was to create a new light-controlled local anesthetic and study its biological activity in animals. A compound with a simple scheme of synthesis was chosen to shift the UV-Vis absorption band towards the visible range of the spectrum and was synthesized for the first time. Some computer calculations were performed to make sure that the aforementioned changes would not lead to loss of biological activity. The micellar form of the new compound was prepared, and in vivo biological studies were carried out in rabbits. The existence of a local anesthetic effect, which disappeared almost completely on irradiation with light (λ = 395 nm), was shown using the surface anesthesia model. Moreover, the possibility of multiple reversible changes in the biological activity of ethercaine under the action of light was demonstrated. The latter compound manifests no local irritating effect, either. The data obtained indicate the prospects for the development of new compounds based on azobenzene for light-controlled local anesthesia.

Tin Carboxylate Complexes of Natural Bacteriochlorin for Combined Photodynamic and Chemotherapy of Cancer è.

Photodynamic therapy (PDT) is currently one of the most promising methods of cancer treatment. However, this method has some limitations, including a small depth of penetration into biological tissues, the low selectivity of accumulation, and hypoxia of the tumor tissues. These disadvantages can be overcome by combining PDT with other methods of treatment, such as radiation therapy, neutron capture therapy, chemotherapy, etc. In this work, potential drugs were obtained for the first time, the molecules of which contain both photodynamic and chemotherapeutic pharmacophores. A derivative of natural bacteriochlorophyll a with a tin IV complex, which has chemotherapeutic activity, acts as an agent for PDT. This work presents an original method for obtaining agents of combined action, the structure of which is confirmed by various physicochemical methods of analysis. The method of molecular modeling was used to investigate the binding of the proposed drugs to DNA. In vitro biological tests were carried out on several lines of tumor cells: Hela, A549, S37, MCF7, and PC-3. It was shown that the proposed conjugates of binary action for some cell lines had a dark cytotoxicity that was significantly higher (8-10 times) than the corresponding metal complexes of amino acids, which was explained by the targeted chemotherapeutic action of the tin (IV) complex due to chlorin. The greatest increase in efficiency relative to the initial dipropoxy-BPI was found for the conjugate with lysine as a chelator of the tin cation relative to cell lines, with the following results: S-37 increased 3-fold, MCF-7 3-fold, and Hela 2.4-fold. The intracellular distribution of the obtained agents was also studied by confocal microscopy and showed a diffuse granular distribution with predominant accumulation in the near nuclear region.

The First Selenoanhydride in the Series of Chlorophyll a Derivatives, Its Stability and Photoinduced Cytotoxicity.

In this work, we obtained the first selenium-containing chlorin with a chalcogen atom in exlocycle E. It was shown that the spectral properties were preserved in the target compound and the stability increased at two different pH values, in comparison with the starting purpurin-18. The derivatives have sufficiently high fluorescence and singlet oxygen quantum yields. The photoinduced cytotoxicity of sulfur- and selenium-anhydrides of chlorin p6 studied for the first time in vitro on the S37 cell line was found to be two times higher that of purpurin-18 and purpurinimide studied previously. Moreover, the dark cytotoxicity increased four-fold in comparison with the latter compounds. Apparently, the increase in the dark cytotoxicity is due to the interaction of the pigments studied with sulfur- and selenium-containing endogenous intracellular compounds. Intracellular distributions of thioanhydride and selenoanhydride chlorin p6 in S37 cells were shown in cytoplasm by diffusion distribution. The intracellular concentration of the sulfur derivative turned out to be higher and, as a consequence, its photoinduced cytotoxicity was higher as well.

Derivatives of Natural Chlorophylls as Agents for Antimicrobial Photodynamic Therapy.

The rapid growth of drug-resistant bacteria all over the world has given rise to a major research challenge, namely a search for alternative treatments to which bacteria will be unable to develop resistance. Photodynamic therapy is an approach of this kind. It involves the use of photosensitizers in combination with visible light at a certain wavelength to excite the former and generate reactive oxygen species. Various synthetic heterocyclic compounds are used as photosensitizers. Of these, derivatives of natural chlorophylls have a special place due to their properties. This review deals with the use of such compounds in antimicrobial PDT.