RESUMO
Photobiological properties of phthalocyanine photosensitizers, namely, clinically approved Photosens and new compounds Holosens and Phthalosens were analyzed on transitional cell carcinoma of the urinary bladder (T24) and human hepatic adenocarcinoma (SK-HEP-1). Photosens is a sulfated aluminum phthalocyanine with the number of sulfo groups 3.4, which is characterized by a high degree of hydrophilicity, slow cellular uptake, localization in lysosomes and the lowest photodynamic activity. Holosens is an octacholine zinc phthalocyanine, a cationic compound with significant charge. Holosens more efficiently enters the cells; it is localized in Golgi apparatus in addition to lysosomes and exhibits a significant inhibitory effect on cell viability upon irradiation. The highest photodynamic activity was demostrated by Phthalosens. Phthalosens is a metal-free analog of Photosens with a number of sulfo groups 2.5, which determines its amphiphilicity. Phthalosens is characterized by the highest rate of cellular uptake through the outer cell membrane, localization in cell membrane as well as in lysosomes and Golgi apparatus, and the highest activity upon irradiation among the photosensitizers studied. In general, changes in the physicochemical properties of Holosens and Phthalosens ensured an increase in their efficiency in vitro compared to Photosens. The features of accumulation, intracellular distribution and their interrelation with photodynamic activity, revealed in this work, indicate the prospects of Phthalosens and Holosens for clinical practice.
Assuntos
Indóis/farmacologia , Fármacos Fotossensibilizantes/química , Linhagem Celular Tumoral , Complexo de Golgi/metabolismo , Humanos , Indóis/farmacocinética , Isoindóis , Lisossomos/metabolismo , Organelas/metabolismo , Compostos Organometálicos/farmacocinética , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacocinética , Compostos de ZincoRESUMO
A numerical algorithm based on a small-angle approximation of the radiative transfer equation (RTE) is developed to reconstruct scattering characteristics of biological tissues from optical coherence tomography (OCT) images. According to the algorithm, biological tissue is considered to be a layered random medium with a set of scattering parameters in each layer: total scattering coefficient, variance of a small-angle scattering phase function, and probability of backscattering, which fully describe the OCT signal behavior versus probing depth. The reconstruction of the scattering parameters is performed by their variation to fit the experimental OCT signal by the theoretical one using a time-saving genetic algorithm. The proposed reconstruction procedure is tested on model media with known scattering parameters. The possibility to estimate scattering parameters from OCT images is studied for various regimes of OCT signal decay. The developed algorithm is applied to reconstruct optical characteristics of epithelium and stroma for normal cervical tissue and its pathologies, and the potential to distinguish between the types of pathological changes in epithelial tissue by its OCT images is demonstrated.
Assuntos
Algoritmos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Refratometria/métodos , Tomografia de Coerência Óptica/métodos , Neoplasias do Colo do Útero/patologia , Colo do Útero/patologia , Simulação por Computador , Diagnóstico Diferencial , Feminino , Humanos , Modelos Biológicos , Imagens de Fantasmas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tomografia de Coerência Óptica/instrumentaçãoRESUMO
The capabilities of diffuse optical spectroscopy for noninvasive assessing of oxygen status in experimental tumors have been demonstrated. Specific features of the distribution of total hemoglobin, oxygenated hemoglobin, deoxygenated hemoglobin, and blood-oxygen saturation were shown on two tumor models having different histological structure and functional characteristics. The results obtained by the optical technique were verified by immunohistochemical study of tissue samples marked with exogenous marker of hypoxia--pimonidazole.