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

Article Article scientifique Article Tunable phosphatase-sensitive stable prodrugs of 5-aminolevulinic acid for tumor fluorescence photodetection fre 2016 author Babic Andréj 742457 author Herceg Viktorija 768015 author Ateb Imene 810668 author Allémann Eric 0000-0002-6598-9521 26730 author Lange Norbert 135650 155-164 10.1016/j.jconrel.2016.05.047 27235981 0168-3659 http://linkinghub.elsevier.com/retrieve/pii/S0168365916303261 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 Dewey 615 31 Section des sciences pharmaceutiques 17 false 883 Technologie pharmaceutique Journal of Controlled Release 235 ed4cce7e-6ee2-4a2c-96d2-458243fb3d21 Article (Accepted version) Public Babic-Tunable-phosphatese-sensitive-prodrugs-of-5-ALA.pdf 792906 application/pdf CC BY-NC openAccess Faculté des sciences / Section des sciences pharmaceutiques

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Tunable phosphatase-sensitive stable prodrugs of 5-aminolevulinic acid for tumor fluorescence photodetection	Journal of Controlled Release			2016	483	536

Archive ouverte UNIGE

Ateb, Imene