Cell specific aptamer-photosensitizer conjugates as a molecular tool in photodynamic therapy

ChemMedChem. 2008 Mar;3(3):425-8. doi: 10.1002/cmdc.200700260.

Abstract

This paper describes the application of a molecular construct of a photosensitizer and an aptamer for photo-therapeutically targeting tumor cells. The key step in increasing selectivity in chemotherapeutic drugs is to create effective molecular platforms that could target cancer cells but not normal cells. Recently, we have developed a strategy via cell-SELEX (Systematic Evolution of Ligands by Exponential Enrichment) to obtain cell specific aptamers using intact viable cells as targets to select aptamers that can recognize cell membrane proteins with high selectivity and excellent affinity. We have identified an aptamer TD05 that only recognizes Ramos cells, a Burkitt’s lymphoma cell line. Here, the high specificity of aptamers in target cell binding and an efficient phototherapy reagent, Ce6, are molecularly engineered to construct a highly selective Aptamer-photosensitizer conjugates (APS) to effectively destroy target cancer cells. Introduction of the APS conjugates followed by irradiation of light selectively destroyed target Ramos cells but not acute lymphoblastic leukemia and myeloid leukemia cell lines. This study demonstrates that the use of cancer specific aptamers conjugated to a photosensitizer will enhance the selectivity of photodynamic therapy. Coupled with the advantages of the cell-SELEX in generating multiple effective aptamers for diseased cell recognition, we will be able to develop highly efficient photosensitizer based therapeutical reagents for clinical applications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Aptamers, Nucleotide / chemical synthesis
  • Aptamers, Nucleotide / pharmacology*
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / pathology
  • Flow Cytometry
  • Fluorescein-5-isothiocyanate
  • Humans
  • Photochemotherapy / methods*
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / pharmacology*
  • Porphyrins / chemical synthesis
  • Porphyrins / pharmacology*

Substances

  • Amines
  • Antineoplastic Agents
  • Aptamers, Nucleotide
  • Photosensitizing Agents
  • Porphyrins
  • phytochlorin
  • Fluorescein-5-isothiocyanate