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Light enhancement of in vitro antitumor activity of galactosylated phthalocyanines

Abstract Background and objectives: Intensive research in the area of photodynamic therapy (PDT) has been made in recent years revealing it as a promising method for the treatment of tumors and inactivation of pathogenic microorganisms. However, for a broader application of this therapy one major challenge, namely a significant improvement of the targeted drug delivery and uptake, still remains. A possible solution of the selectivity problem could be the application of specifically functionalized photosensitizers, in particular phthalocyanine dyes. Materials and methods: Water-soluble Zn(II) phthalocyanines (ZnPcs) with four galactose moieties on non-peripheral and peripheral positions and a non-substituted Zn(II) phthalocyanine were studied for in vitro antitumor activity on three breast cancer cell lines (MCF-7, MDA-MB-231 and HBL-100). The influence of the exposure to ultraviolet (UV) (365 nm) and red (635 nm) light in non-therapeutic doses on the cellular uptake, binding and subcellular localization of three photosensitizers was investigated by confocal laser scanning microscopy. In addition, phototoxicity studies with the tested phthalocyanines on the non-tumorigenic mouse embryo cell line Balb c/3T3 (clone 31) were carried out. Results: The results indicate that the pre-treatment, namely exposure to UV or red light, influences the localization properties of the used dyes. The positions of galactose units to the ZnPc ring also influenced the uptake, localization and the photodynamic response of breast cancer cells. The results show that the galactose substitution, together with exposure to UV or red light in non-therapeutic doses, are important factors for the photodynamic effect. Conclusion: Experimental PDT with galactose-substituted ZnPcs accompanied by UV and red light pre-irradiation leads to a higher photodynamic effect towards breast tumor cells. Thus, the investigated galactopyranosyl-substituted phthalocyanines could be used as a part of the design of intelligent, stimuli-responsive nanosystems for medical applications.