Scientific article
Open access

Tunable phosphatase-sensitive stable prodrugs of 5-aminolevulinic acid for tumor fluorescence photodetection

Published inJournal of Controlled Release, vol. 235, p. 155-164
Publication date2016

5-Aminolevulinic acid (5-ALA) has been at the forefront of small molecule based fluorescence-guided tumor resection and photodynamic therapy. 5-ALA and two of its esters received marketing authorization but suffer from several major limitations, namely low stability and poor pharmacokinetic profile. Here, we present a new class of 5-ALA derivatives aiming at the stabilization of 5-ALA by incorporating a phosphatase sensitive group, with or without self-cleavable linker. Compared to 5-ALA hexyl ester (5-ALA-Hex), these compounds display an excellent stability under acidic, basic and physiological conditions. The activation and conversion into the 5-ALA is controlled and can be structure-tailored. The prodrugs display reduced acute toxicity compared to 5-ALA-Hex with superior dose response profiles of protoporphyrin IX synthesis and fluorescence intensity in human glioblastoma cells in vitro. Clinically relevant fluorescence kinetics in vivo shown in U87MG glioblastoma spheroid tumor model in chick embryos provide a solid basis for their further development and translation to clinical fluorescence guided tumor resection and photodynamic therapy.

  • 5-Aminolevulinic acid
  • Alkaline phosphatase
  • Photodynamic therapy
  • Prodrugs
  • Tumor photodetection
Citation (ISO format)
BABIC, Andréj et al. Tunable phosphatase-sensitive stable prodrugs of 5-aminolevulinic acid for tumor fluorescence photodetection. In: Journal of Controlled Release, 2016, vol. 235, p. 155–164. doi: 10.1016/j.jconrel.2016.05.047
Main files (1)
Article (Accepted version)
ISSN of the journal0168-3659

Technical informations

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