Luminescent Iridium-Peptide Nucleic Acid Bioconjugate as Photosensitizer for Singlet Oxygen Production toward a Potential Dual Therapeutic Agent

A novel bioorganometallic PNA conjugate (<b>Ir-PNA</b>) was synthesized by covalently bonding a model PNA tetramer to a luminescent bis-cyclometalated Ir(III) complex that acted as a photosensitizer under light irradiation to generate singlet oxygen (¹O₂). The conjugate was prepared using an Ir complex bearing the 1,10-phenanthroline ligand functionalized with either a free primary amine (<b>Ir-NH</b>_<b>2</b>) or a carboxyl group (<b>Ir-COOH</b>) for the conjugation to PNA. The photophysical studies on the <b>Ir-COOH</b> and the <b>Ir-PNA</b> demonstrated that the luminescent properties were maintained after the conjugation of the Ir fragment to PNA. Furthermore, the abilities to produce ¹O₂ of <b>Ir-COOH</b> and <b>Ir-PNA</b> were confirmed in a cuvette under visible light irradiation employing 1,5-dihydroxynaphthalene as a reporter, and the measured singlet oxygen quantum yield (Φ_Δ) supported the <b>Ir-PNA</b> conjugate efficacy as a photosensitizer (Φ_Δ = 0.54). Two-photon absorption microscopy on HeLa cells revealed that <b>Ir-PNA</b> localized in both the cytosol and nucleus, suggesting its potential as an intracellular carrier for PNA. Cytotoxicity assays by MTT tests showed that <b>Ir-PNA</b> was nontoxic in the absence of light, but induced cell death (EC₅₀ = 18 μM) after UV irradiation. Overall, the <b>Ir-PNA</b> conjugate represents a promising system for the intracellular delivery of the PNA and its application in PDT.