Nuclear targeting of chlorin e6 enhances its photosensitizing activity

Tamara V. Akhlynina, David A. Jans, Andrey A. Rosenkranz, Natalya V. Statsyuk, Irina Y. Balashova, Gabor Toth, Imre Pavo, Andrey B. Rubin, Alexander S. Sobolev

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Although photosensitizers, molecules that produce active oxygen species upon activation by visible light, are being extensively used in photodynamic therapy to treat cancer and other clinical conditions, problems include normal cell and tissue damage and associated side effects, which are attributable in part to the fact that cytotoxic effects are largely restricted to the plasma membrane. We have previously shown that the photosensitizer chlorin e6 has significantly higher photosensitizing activity when present in conjugates containing specific ligands and thus able to be internalized by receptor-expressing cells. In this study we use insulin-containing conjugates to which variants of the simian virus SV40 large tumor antigen nuclear localization signal (NLS) were linked to target chlorine E6 to the nucleus, a hypersensitive site for active oxygen species- induced damage. NLSs were either included as peptides cross-linked to the carrier bovine serum albumin or encoded within the sequence of a β- galactosidase fusion protein carrier. The results for photosensitization demonstrate clearly for the first time that NLSs increase the photosensitizing activity of chlorin e6, maximally reducing the EC50 by a factor of over 2000-fold. This has wide-reaching implications for achieving efficient cell type-specific photodynamic therapy.

Original languageEnglish
Pages (from-to)20328-20331
Number of pages4
JournalThe Journal of Biological Chemistry
Issue number33
Publication statusPublished - 15 Aug 1997
Externally publishedYes

Cite this

Akhlynina, T. V., Jans, D. A., Rosenkranz, A. A., Statsyuk, N. V., Balashova, I. Y., Toth, G., Pavo, I., Rubin, A. B., & Sobolev, A. S. (1997). Nuclear targeting of chlorin e6 enhances its photosensitizing activity. The Journal of Biological Chemistry, 272(33), 20328-20331.