Assessing the Role of Cell Membrane Transporters in 5-Aminolevulinic Acid-Mediated Protoporphyrin Fluorescence and Photodynamic Therapy

Abstract

5-ALA is a prodrug that has become widely used in photodynamic therapy and optic imaging for patients with high-grade glioma. It is taken up by cancer cells and metabolized in the heme biosynthesis pathway to PPIX, which exhibits red fluorescence and photosensitizing activity. Several transporters are involved in 5-ALA uptake and PPIX transport, including GAT, TSPO, and ABC transporters. These transporters influence the production and accumulation of PPIX, affecting the tumor’s fluorescence intensity. The role of transporters was assessed by measuring PPIX levels. GABA and taurine exert a significant influence on PPIX levels, suggesting the involvement of these transporters in ALA-PPIX fluorescence. Among porphyrin transporters, the inhibition of ABCG2 led to a significant increase in intracellular PPIX levels, thereby enhancing PDT efficacy. ABCB1 and TSPO did not significantly affect PPIX levels. These results indicate that among the investigated transporters ABCG2, and GABA transporters play a primary role in 5-ALA-mediated PPIX fluorescence.