Confocal microscopy and colocalization analysis using Pearson correlation coefficients were used to show that esterified chlorin e 6 derivatives and their liposomal forms are mainly localized in the endoplasmic reticulum, Golgi complexes, cell mitochondria, and levels of their localization in lysosomes are low. Cellular uptake and accumulation kinetics of chlorin e 6 derivatives were strongly depended on the type of pharmacological formulation used for photosesitizers administration, while intracellular localization was independent on the formulation. Differences in the photodynamic activity and sensitization mechanisms for chlorin e 6 derivatives and their liposomal forms were shown when compared to those of chlorin e 6 photosensitizers in K562 cells. It is assumed that the observed differences in the mechanisms of cellular damage are to a greater extent due to specific photosensitizer localization.
Photodynamic therapy represents a more targeted and less invasive alternative cancer treatment to traditional modalities. Temoporfin, as with many photosensitizers, is given by injection into a vein, and its subsequent fate is largely determined by the binding to plasma proteins and interaction with endothelial and blood cells. Thus, it is essential to be able to control and to alter the biodistribution of temoporfin in blood. In the present study, we evaluated the effect of co-administration of temoporfin with randomly methylated β-CD (Me-β-CD) on the distribution of temoporfin in the main subpopulations of blood cells of healthy donors using absorbance spectrophotometry and flow cytometry. We showed that cell-bound temoporfin fraction in blood strongly depends on the concentration of Me-β-CD. In fact, the accumulation of temoporfin in white blood cells was more sensitive than that in red blood cells, due to the higher volume of membranous organelles in white blood cells. Finally, we demonstrated that Me-β-CD significantly increases cellular uptake of temoporfin cancer human Burkitt′s lymphoma Raji cells. The presence of Me-β-CD resulted in a spotted pattern of temoporfin distribution in the plasma membrane compartment. Our results clearly demonstrated that β-CDs derivatives provide new options to modulate temoporfin biodistribution in blood.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.