Photodynamic therapy of human glioma spheroids: A comparative study of the effectiveness of 5-aminolevulinic acid and its esters

Although 5-aminolevulinic acid (ALA) has several advantages over other photosensitizers, its hydrophilic nature gives rise to relatively poor transport across cell membranes. Esterification of ALA is a commonly used strategy to improve the effectiveness of ALA. In this study, the effectiveness of photodynamic therapy (PDT) in human glioma spheroids incubated in ALA, or ALA esters, is investigated. Spheroid survival and growth are monitored following PDT at representative drug concentrations and light fluences. It is shown that the response of human glioma spheroids to PDT with lipophilic ester derivatives, such as benzyl-ALA and hexyl-ALA, is equivalent to that observed with ALA, however, this equivalency is observed for ester concentrations 10 to 20 times lower than the parent compound