Bioorganometallic Iridium(III)-peptide nucleic acid conjugates as potential dual-action compounds for cancer treatment

Peptide nucleic acids (PNAs) are mimics of native nucleic acid structures able to target natural DNA or RNA with high sequence specificity and affinity and are therefore potential excellent candidates in diagnostics, antisense and antigene therapy.[1] In place of the ribose phosphodiester backbone of DNA and RNA, PNAs contain a pseudopeptide backbone, composed of N-(2-aminoethyl)glycine units, on which the four nucleobases are inserted. PNAs display high chemical and enzymatic stability towards nucleases. Unmodified PNAs exhibit low cellular uptake and this feature constitutes a drawback towards its effective use in therapy. One of the strategies to overcome this problem is the conjugation of PNA to metal complexes that can modify their intrinsic physico-chemical and spectroscopic properties.[2] In our ongoing studies on PNA we have focused our attention on the development of novel bioorganometallic iridium-PNA conjugates that can be employed for the synergic treatment of cancer, combining antisense therapy based on PNAs and photodynamic therapy (PDT) related to the use of a photosensitizer, such as the Ir(III) complex[3] reported in Figure, which is able to generate cytotoxic singlet oxygen (1O2) under appropriate excitation light. This complex is also able to penetrate cell membrane, thus it could act as a carrier for the intracellular delivery of PNAs. Furthermore, photoluminescence properties of the Ir(III) complex can be triggered by two-photon excitation, which allows to obtain less cellular damage and deeper in vivo light penetration. In this communication we will report our preliminary studies on the synthesis and the photophysical characterization of the Ir(III)-PNA conjugate reported in Figure, in which a PNA decamer containing all the four nucleobases has been selected as model PNA sequence