Targeted intracellular delivery of photosensitizers to enhance photodynamic efficiency

Andrey A. Rosenkranz, David A. Jans, Alexander S. Sobolev

Research output: Contribution to journalArticleResearchpeer-review

162 Citations (Scopus)

Abstract

Photodynamic therapy (PDT) is a novel treatment, used mainly for anticancer therapy, that depends on the retention of photosensitizers (PS) in tumour cells and irradiation of the tumour with appropriate wavelength light· Photosensitizers are molecules such as porphyrins and chlorins that, on photoactivation, effect strongly locaized oxidative damage within target cells. The PS used for PDT localize in various cytoplasmic membranous structures, but are not found in the most vulnerable intracellular sites for reactive oxygen species, such as the cell nucleus. The experimental approaches discussed in the present paper indicate that it is possible to design highly efficient molecular constructs, PS carriers, with specific modules conferring cell-specific targeting, internalization, escape from intracellular vesicles and argeting to the most vulnerable intracellular, compartments, such as the nucleus. Nuclear targeting of these PS-carrying constructs results in enhanced photodynamic activity, maximally · about 2500-fold that of free PS. Future work is intended to optimize this approach to the point at which tumour · cells can be killed rapidly and efficiently, while minimizing normal cell and tissue damage.

Original languageEnglish
Pages (from-to)452-464
Number of pages13
JournalImmunology and Cell Biology
Volume78
Issue number4
DOIs
Publication statusPublished - 11 Sep 2000
Externally publishedYes

Keywords

  • Nuclear import
  • Nuclear localization sequence
  • Photodynamic therapy
  • Photosensitizer
  • Receptor-mediated endocytosis
  • Targeted delivery

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