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It has been found that the photosensitizer 131-[2-(guanidinyl)ethylamino] chlorin e6 dimethyl ester accumulates predominantly in lysosomes, partially in endosomes, and does not accumulate in mitochondria of human lung adenocarcinoma A549 cells. The primary photocytotoxic effect of the photosensitizer is associated with the damage to lysosomes and its release into the cytoplasm. In the cytoplasm, the photosensitizer is uniformly distributed in complexes with membrane structures, which serve as the secondary targets of its photoinduced effect. Time-dependent morphological signs of the development of paraptosis have been revealed, which indicate the photodynamic damage to the endoplasmic reticulum as the secondary mechanism of the photocytotoxic effect of the photosensitizer. At this stage, one more change in the potential cellular targets of the photosensitizer occurs: it concentrates in cytoplasmic and nuclear membranes, in the membranes of numerous vacuoles, and in lysosomes, which apparently continue to form during the development of paraptosis. Thus, the chlorin е6 derivative, as a representative of hydrophobic photosensitizers with the intracellular targeting to lysosomes, has a two- or three-stage process of photodynamic action with consecutive changes in cellular targets. [ABSTRACT FROM AUTHOR]

The production technology for nanoparticles based on a copolymer of lactic and glycolic acids (PLGA) containing dipropoxybacteriopurpurinimide (DPBPI) and intended for photodynamic therapy of malignant neoplasms of various etiology is optimized. An approach to reducing the average diameter of the resulting nanoparticles is proposed. The obtained DPBPI-PLGA nanoparticles had average diameter 142.3 ± 2.7 nm; ξ-potential 17.1 ± 3.42 mV; polydispersity index 0.095; and total DPBPI content in DPBPI-PLGA particles 17.4 mg/g. DPBPI-PLGA nanoparticles were produced for biological tests. The intracellular distribution of DPBPI in DPBPI-PLGA nanoparticles was studied in in vitro experiments on A549 cells. DPBPI accumulation kinetics in and elimination kinetics from the cells were also studied. DPBPI-PLGA showed high photoinduced cytotoxicity in in vitro experiments. DPBPI-PLGA nanoparticles exhibited antitumor activity in in vivo experiments in an S37 murine soft tissue sarcoma model. [ABSTRACT FROM AUTHOR]

Boron neutron-capture therapy of cancer is based on the ability of the B isotope to capture thermal neutrons; it is one of the most promising techniques in radiation therapy. The high content and selective accumulation of B in the tumor tissue are the most important prerequisites for its efficacy. The purpose of this study was to determine the biodistribution of cobalt bis(dicarbollide) conjugates with chlorin e amino amide derivatives. Experiments were carried out in Balb/c mice with transplanted CT-26 murine colon carcinoma. Boron-containing conjugates were injected into the tail vein at a dose of 10 mg/kg. The conjugate accumulation in tumor tissue and organs was studied by laser scanning microscopy. Excitation was performed at the wavelength of 514 nm; the signals were recorded in the range of 560-710 nm in increments of 10 nm. To evaluate the amount of the boron conjugate, we calculated the intensity of the fluorescence signal of the samples under investigation. At 3 h after administration of the agent, a high level of fluorescence was observed in the liver, spleen, and lung. The tumor/muscle accumulation ratio was approximately 3. The study demonstrated that boron derivatives of chlorin e are promising agents for boron neutron-capture therapy. [ABSTRACT FROM AUTHOR]

The spectral-kinetic study of deactivation processes of the excited singlet and triplet states of indocarbocyanine dyes (Dye1, Dye2, and Dye3) and chlorin e6 (Chl), which constitute dyads I–III (Dye-Chl), was performed. In dyad Dye1-Chl, deactivation of the excited singlet state of the dye occurs mainly due to inductive-resonance energy transfer to Chl with the efficiency of 97%. The consequence of the energy transfer is population of the triplet level of Chl due to singlet-triplet intersystem crossing. In dyads Dye2-Chl and Dye3-Chl, deactivation of the excited singlet state of Chl occurs mainly due to inductive-resonance energy transfer to the dye molecule. The transfer efficiency is 96% for dyad Dye2-Chl and 85% for dyad Dye3-Chl with the shorter length of the -(CH2)-spacer, which binds the Dye3 and Chl molecules. In solutions of Chl and Dye2 (Dye3) mixtures in acetonitrile, exchange-resonance energy transfer occurs from the triplet level of Chl to the Dye2 (Dye3) molecule and electron transfer takes place involving triplet molecules of Dye2 (Dye3). [ABSTRACT FROM AUTHOR]

The spectral-kinetic study of deactivation processes of the excited singlet and triplet states of indocarbocyanine dyes (Dye1, Dye2, and Dye3) and chlorin e6 (Chl), which constitute dyads I–III (Dye-Chl), was performed. In dyad Dye1-Chl, deactivation of the excited singlet state of the dye occurs mainly due to inductive-resonance energy transfer to Chl with the efficiency of 97%. The consequence of the energy transfer is population of the triplet level of Chl due to singlet-triplet intersystem crossing. In dyads Dye2-Chl and Dye3-Chl, deactivation of the excited singlet state of Chl occurs mainly due to inductive-resonance energy transfer to the dye molecule. The transfer efficiency is 96% for dyad Dye2-Chl and 85% for dyad Dye3-Chl with the shorter length of the -(CH2)-spacer, which binds the Dye3 and Chl molecules. In solutions of Chl and Dye2 (Dye3) mixtures in acetonitrile, exchange-resonance energy transfer occurs from the triplet level of Chl to the Dye2 (Dye3) molecule and electron transfer takes place involving triplet molecules of Dye2 (Dye3). [ABSTRACT FROM AUTHOR]