RESUMO
HYPOTHESIS: Hydrophobic bacteriochlorin based photosensitizer (PS) can be effectively immobilized on MNP covered by human serum albumin (HSA). PS loading into MNP protein shell allows solubilizing PS in water solution without altering its photodynamic activity. MNP@PS can serve as diagnostic tool for tracking PS delivery to tumor tissues by MRI. EXPERIMENTS: Immobilization on MNP-HSA-PEG was performed by adding PS solution in organic solvents with further purification. MNP@PS were characterized by DLS, HAADF STEM and AFM. Absorbance and fluorescence measurements were used to assess PS photophysical properties before and after immobilization. MNP@PS internalization into CT26 cells was investigated by confocal microscopy in vitro and MRI/IVIS were used for tracking MNP@PS delivery to tumors in vivo. FINDINGS: MNP@PS complexes were stable in water solution and retained PS photophysical activity. The length of side chain affected MNP@PS size, loading capacity and cell internalization. In vitro testing demonstrated MNP@PS delivery to cancer cells followed by photoinduced toxicity. In vivo studies confirmed that as-synthetized complexes can be used for MRI tracking over drug accumulation in tumors.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita/química , Fármacos Fotossensibilizantes/administração & dosagem , Porfirinas/administração & dosagem , Animais , Antibióticos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas de Magnetita/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Albumina Sérica Humana/química , Propriedades de SuperfícieRESUMO
This paper presents a primary screening of bacteriochlorin-type compounds with aminoamide, propyl and carbohydrate substituents aimed for development a new generation photosensitizers (PS) for photodynamic therapy of malignant tumors. Absorption and fluorescence spectral characteristics of the compounds, their storage stability in solutions under dark conditions and light exposure, photo-induced and dark cytotoxicity against human HEp2 tumor cells have been studied. It has been shown that the dyes with aminoamide substituents have an absorbtion maximum at 754±2 nm in the long wavelength region and they are not stable during storage (the specific fluorescence intensity decreased by 33-56% during 24 hours). The long wavelength region absorption of the propyl and carbohydrate substituted compounds varied in the range 780-831 nm, they were stable in solutions during storage and under light irradiation. Except the dye with a carbohydrate residue in the exocycle E, all PS exhibited the high photo-induced activity and low level of the dark cytotoxicity. The highest photo-induced cytotoxicity was observed for compounds with aminoamide substituents inthe macrocyclic ring (IC 50 values ranged from 17 nM to49 nM after 2 hour incubation with PS followed by exposure to the 10 J/cm 2 dose of red light). Taking into account the totality of the physico-chemical and biological properties, as well as manufacturability of production, O-propyloxime-N-propoxybacteriopurinimide methyl ester was chosen as the most promising candidate compound for further investigations.
Assuntos
Neoplasias/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Fármacos Fotossensibilizantes/química , Porfirinas/químicaRESUMO
The territorial spread of Tahyna, Batai, Sindbis, West Nile fever and Crimean-Congo hemorrhagic fever viruses throughout the Saratov region in 1998 - 2000 was analyzed. The characteristics of the epizootic activity of the natural foci of these arboviruses in different landscape zones (temperate forest-steppes, steppes and semi-deserts) were calculated. The species composition of small mammals, the natural reservoirs of the causative agents of arbovirus infections, was determined.
Assuntos
Arbovírus/isolamento & purificação , Reservatórios de Doenças/virologia , Animais , Antígenos Virais/análise , Infecções por Arbovirus/epidemiologia , Arbovírus/imunologia , Vírus Bunyamwera/imunologia , Vírus Bunyamwera/isolamento & purificação , Ecossistema , Vírus da Encefalite da Califórnia/imunologia , Vírus da Encefalite da Califórnia/isolamento & purificação , Vírus da Febre Hemorrágica da Crimeia-Congo/imunologia , Vírus da Febre Hemorrágica da Crimeia-Congo/isolamento & purificação , Mamíferos/virologia , Federação Russa , Sindbis virus/imunologia , Sindbis virus/isolamento & purificação , Vírus do Nilo Ocidental/imunologia , Vírus do Nilo Ocidental/isolamento & purificaçãoRESUMO
Information on V. cholerae eltor isolated in the focus of cholera in Kazan in 2001 at different periods of the outbreak is presented. The identity of strains isolated from patients, vibriocarriers and environmental objects, including their antibioticograms (sensitivity to cyprofloxacin and resistance to trimethoprim--sulfamethoxazole, streptomycin, furazolidone and nalidixic acid, which may be regarded as markers), is shown. Variable tandem repetitions in the DNA of 30 isolates strains of different origin have been determined. The results of this determination make it possible to classify all these strains as one genotype, which confirms the suggestion on the circulation of one subclone of the infective agent of cholera in the focus. As revealed in this investigation, the isolated strains are labile with respect to diagnostic phage eltor, while ctx+ strains are resistant to phage eltor ctx+.
Assuntos
Cólera/metabolismo , Vibrio cholerae/genética , Vibrio cholerae/metabolismo , Antibacterianos/metabolismo , Antibacterianos/uso terapêutico , Biomarcadores , Cólera/tratamento farmacológico , Cólera/epidemiologia , Ciprofloxacina/uso terapêutico , Resistência Microbiana a Medicamentos/genética , Furazolidona/metabolismo , Genótipo , Humanos , Ácido Nalidíxico/metabolismo , Federação Russa/epidemiologia , Estreptomicina/metabolismo , Sulfametoxazol/metabolismo , Resistência a Trimetoprima/genética , Vibrio cholerae/classificação , Vibrio cholerae/efeitos dos fármacos , Vibrio cholerae/isolamento & purificaçãoRESUMO
There was revealed a regular reduction of plague, tularemia and pseudotuberculosis bacteria count in the lungs of guinea pigs the first 12 hours after aerosol infection. Generalization of the infectious process and associated septicemia occurred in pulmonary plague and pulmonary tularemia on the 1st-2nd day, and in pulmonary pseudotuberculosis - on the 4th-5th day. Limits of accumulation of the causative agents in the organs and the blood at various stages of the infectious process were established.