Nuclear targeting of chlorin e6 enhances its photosensitizing activity

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

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

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
JournalJournal of Biological Chemistry
Volume272
Issue number33
DOIs
Publication statusPublished - Aug 15 1997

Fingerprint

Photodynamic therapy
Photosensitizing Agents
Photochemotherapy
Reactive Oxygen Species
Galactosidases
Photosensitivity Disorders
Nuclear Localization Signals
Simian virus 40
Neoplasm Antigens
Cell membranes
Bovine Serum Albumin
Viruses
Carrier Proteins
Fusion reactions
Chemical activation
Cell Membrane
Insulin
Tissue
Ligands
Light

ASJC Scopus subject areas

  • Biochemistry

Cite this

Akhlynina, T. V., Jans, D. A., Rosenkranz, A. A., Statsyuk, N. V., Balashova, I. Y., Tóth, G., ... Sobolev, A. S. (1997). Nuclear targeting of chlorin e6 enhances its photosensitizing activity. Journal of Biological Chemistry, 272(33), 20328-20331. https://doi.org/10.1074/jbc.272.33.20328

Nuclear targeting of chlorin e6 enhances its photosensitizing activity. / Akhlynina, Tamara V.; Jans, David A.; Rosenkranz, Andrey A.; Statsyuk, Natalya V.; Balashova, Irina Y.; Tóth, G.; Pavo, Imre; Rubin, Andrey B.; Sobolev, Alexander S.

In: Journal of Biological Chemistry, Vol. 272, No. 33, 15.08.1997, p. 20328-20331.

Research output: Contribution to journalArticle

Akhlynina, TV, Jans, DA, Rosenkranz, AA, Statsyuk, NV, Balashova, IY, Tóth, G, Pavo, I, Rubin, AB & Sobolev, AS 1997, 'Nuclear targeting of chlorin e6 enhances its photosensitizing activity', Journal of Biological Chemistry, vol. 272, no. 33, pp. 20328-20331. https://doi.org/10.1074/jbc.272.33.20328
Akhlynina TV, Jans DA, Rosenkranz AA, Statsyuk NV, Balashova IY, Tóth G et al. Nuclear targeting of chlorin e6 enhances its photosensitizing activity. Journal of Biological Chemistry. 1997 Aug 15;272(33):20328-20331. https://doi.org/10.1074/jbc.272.33.20328
Akhlynina, Tamara V. ; Jans, David A. ; Rosenkranz, Andrey A. ; Statsyuk, Natalya V. ; Balashova, Irina Y. ; Tóth, G. ; Pavo, Imre ; Rubin, Andrey B. ; Sobolev, Alexander S. / Nuclear targeting of chlorin e6 enhances its photosensitizing activity. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 33. pp. 20328-20331.
@article{2e2044be80904e10a52c278c6d7c6783,
title = "Nuclear targeting of chlorin e6 enhances its photosensitizing activity",
abstract = "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.",
author = "Akhlynina, {Tamara V.} and Jans, {David A.} and Rosenkranz, {Andrey A.} and Statsyuk, {Natalya V.} and Balashova, {Irina Y.} and G. T{\'o}th and Imre Pavo and Rubin, {Andrey B.} and Sobolev, {Alexander S.}",
year = "1997",
month = "8",
day = "15",
doi = "10.1074/jbc.272.33.20328",
language = "English",
volume = "272",
pages = "20328--20331",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "33",

}

TY - JOUR

T1 - Nuclear targeting of chlorin e6 enhances its photosensitizing activity

AU - Akhlynina, Tamara V.

AU - Jans, David A.

AU - Rosenkranz, Andrey A.

AU - Statsyuk, Natalya V.

AU - Balashova, Irina Y.

AU - Tóth, G.

AU - Pavo, Imre

AU - Rubin, Andrey B.

AU - Sobolev, Alexander S.

PY - 1997/8/15

Y1 - 1997/8/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0030846556&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030846556&partnerID=8YFLogxK

U2 - 10.1074/jbc.272.33.20328

DO - 10.1074/jbc.272.33.20328

M3 - Article

C2 - 9252335

AN - SCOPUS:0030846556

VL - 272

SP - 20328

EP - 20331

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 33

ER -