Comparative Studies of the Cellular Uptake, Subcellular Localization, and Cytotoxic and Phototoxic Antitumor Properties of Ruthenium(II)-Porphyrin Conjugates with Different Linkers

Six water-soluble free-base porphyrin-Ru(II) conjugates, 1–3, and Zn(II) porphyrin-Ru(II) conjugates, 4–6, with different linkers between the hydrophobic porphyrin moiety and the hydrophilic Ru(II)-polypyridyl complex, have been synthesized. The linear and two-photon-induced photophysical properties of these conjugates were measured and evaluated for their potential application as dual in vitro imaging and photodynamic therapeutic (PDT) agents. Conjugates 1–3, with their high luminescence and singlet oxygen quantum yields, were selected for further study of their cellular uptake, subcellular localization, and cytotoxic and photocytotoxic (under linear and two-photon excitation) properties using HeLa cells. Conjugate 2, with its hydrophobic phenylethynyl linker, was shown to be highly promising for further development as a bifunctional probe for two-photon (NIR) induced PDT and in vitro imaging. Cellular uptake and subcellular localization properties were shown to be crucial to its PDT efficacy.