A Study on the Photobleaching Effect of 5-ALA Conjugated Gold Nanoparticles in a CT26 Tumor Model During Photodynamic Therapy

Introduction During the process photodynamic therapy (PDT), bleaching of photosensitizer induced by irradiation and generation of reactive oxygen species (ROS) can provide some information concerning the efficiency of treatment. Since gold nanoparticles (GNPs) have been highlighted as efficient drug delivery systems, in this study, by utilizing GNPs conjugated with 5 aminolevulinic acid (5-ALA-GNPs), the photobleaching of ALA-induced protoporphyrin IX (PpIX) was estimated on a colon carcinoma tumor model. Materials and Methods CT26 tumor models were prepared by subcutaneous injection of 5×105 cells into the right flank of Balb/c inbred mice. To estimate the time required to reach maximum concentration of PpIX in the tumors, the fluorescence signal of PpIX was monitored and PDT was performed by intratumoral injection of 5-ALA-GNPs, GNPs, and 5-ALA in separated groups for 15 min with a cycle of 5 min irradiation and 1 min darkness. The photobleaching rate was calculated from recorded fluorescence signals at the darkness intervals. Results The maximum fluorescence of PpIX was recorded 3 and 5 hr after injection of 5-ALA and 5-ALA-GNPs, respectively. Despite the low PpIX accumulation in tumors receiving conjugate, the photobleaching rate of PpIX was determined to be higher than 5-ALA. The reduction of the fluorescence signal due to 5-ALA-GNPs clearance was higher than that of 5-ALA. Conclusion Administration of 5-ALA-GNPs, intensification of ROS generating and the subsequent elevation of photobleaching results in higher treatment efficiency. Also, more rapid clearance of PpIX has an important implication in clinical application of 5-ALA-GNPs that decreases the undesirable effects on healthy tissues.

Keywords:

5 -ALA-Conjugated Gold Nanoparticles , CT26 Tumor Model , Photobleaching , Photodynamic Therapy