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Design, synthesis and in vitro evaluation of β-glucuronidase-sensitive prodrug of 5-aminolevulinic acid for photodiagnosis of breast cancer cells

Published inBioorganic Chemistry, vol. 78, p. 372-380
Publication date2018
Abstract

Treatment of cancer cells by clinically approved hexyl ester of 5-aminolevulinic acid (ALA-Hex) induces accumulation of fluorescent porphyrins in tumors. This allows fluorescence photodiagnosis (PD) of bladder cancer by blue light illumination. However, PD of other cancers is hampered by acute toxicity of the compound limiting its use to local applications. We have designed and synthesized a new prodrug of ALA-Hex that tackles the stability-activity paradox of amino-modified 5-ALA prodrugs. The glucuronide prodrug Glu-ALA-Hex demonstrates excellent stability under physiological conditions and activation in the presence of the target enzyme. β-glucuronidase-triggered release of 5-ALA is programmed to yield fluorescence in tumor environment with elevated β-glucuronidase activity, a characteristic of many solid tumors. Glu-ALA-Hex produces similar levels of fluorescence as ALA-Hex in breast cancer MCF7 cells in vitro but with much lower non-specific cell toxicity.

Keywords
  • 5-Aminolevulinic acid
  • Prodrugs
  • Beta-glucuronidase
  • Fluorescence
  • Photodiagnosis
  • Breast cancer
Citation (ISO format)
HERCEG, Viktorija et al. Design, synthesis and in vitro evaluation of β-glucuronidase-sensitive prodrug of 5-aminolevulinic acid for photodiagnosis of breast cancer cells. In: Bioorganic Chemistry, 2018, vol. 78, p. 372–380. doi: 10.1016/j.bioorg.2018.03.020
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Article (Accepted version)
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ISSN of the journal0045-2068
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Technical informations

Creation04/11/2018 4:37:00 PM
First validation04/11/2018 4:37:00 PM
Update time03/15/2023 8:14:15 AM
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