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Photochemical Internalization of a Peptide Nucleic Acid Targeting the Catalytic Subunit of Human Telomerase¹

Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori di Milano, 20133 Milan, Italy [M. F., R. V., M. G. D., N. Z.]; Department of Biophysics, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway [M. F., K. B., L. P.]; and Center of Excellence for Biomedical Research, University of Genoa, 16132 Genoa, Italy [E. M., U. B.]

Because peptide nucleic acids (PNAs) are poorly taken up by mammalian cells, strategies need to be developed for their intracellular delivery. In the present study, we demonstrated the possibility to efficiently release a naked PNA targeting the catalytic component of human telomerase reverse transcriptase (hTERT-PNA) into the cytoplasm of DU145 prostate cancer cells through the photochemical internalization approach. After light exposure, cells treated with the hTERT-PNA and photosensitizer TPPS_2a showed a marked inhibition of telomerase activity and a reduced cell survival, which was not observed after treatment with hTERT-PNA alone. Moreover, in a direct comparison, photochemical internalization technology proved to be more efficient to internalize the hTERT-PNA than an HIV-Tat protein-based approach.

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