The combination of photodynamic and targeted therapeutic approaches seems to be a promising strategy for increasing the therapeutic effect of cancer treatment. The aim of this work was to evaluate the potential of a combined agent, which is a conjugate of a zinc complex of photosensitizer chlorin e6 with tyrosine kinase inhibitor vandetanib (ZnChl-Vd). It was shown that ZnChl-Vd has intense absorption and fluorescence in the red region of the spectrum with a quantum yield of fluorescence of about 2% and a singlet oxygen quantum yield of about 20%. In vitro experiments showed intensive accumulation of ZnChl-Vd in cells of human epidermoid carcinoma A-431 with localization in lysosomes and Golgi apparatus. The pronounced photoinduced cytotoxic effect of the conjugate at submicromolar concentrations was shown. In vivo studies demonstrated the selective accumulation of ZnChl-Vd in the xenograft tumors; irradiation of tumors (50 J/cm²) led to profound tumor regression from their initial volume. In the dark, ZnChl-Vd ability to inhibit tumor growth up to 50% compared to control untreated group evidence the contribution of targeted irradiation-independent mechanism of ZnChl-Vd action. The results indicate high potential of ZnChl-Vd as an anticancer agent combining the activity of a photosensitizer and a target agent.

The research was supported by State assignment in Research scientific laboratory of "Chemistry of natural products and their synthetic analogues" of Scientific Educational Centre "Technoplatform 2035", the Russian Foundation for Basic Research (Grant No. 21-73-10230) and the Ministry of Science and Higher Education of the Russian Federation (State Assignment No. 729-2020-0061).