Author: Lili Chen, Dusica Cvetkovic, Tristan K. Gaddis, Chang Ming Charlie Ma, Dae-Myoung Yang 👨🔬
Affiliation: Fox Chase Cancer Center 🌍
Purpose:
Recent studies have shown that combining photosensitizers with radiation therapy can enhance tumor control while reducing damage to normal tissues, a technique known as Radiodynamic Therapy (RDT). This in vitro investigation compares the biocompatibility of 5-aminolevulinic acid (5-ALA) and acridine orange (AO) with two cell lines and evaluates their efficacy as RDT sensitizers.
Methods:
Human breast adenocarcinoma (MCF7) and prostate adenocarcinoma (PC-3) cell lines were cultured to determine the biocompatibility and RDT sensitizer potential of 5-ALA and AO. Biocompatibility was evaluated with PrestoBlue assays across various concentrations for both cell lines. After determining optimal sensitizer concentrations, cells were seeded in T-25 flasks and irradiated at doses of 2 and 4 Gy, with experiments performed in triplicate. Clonogenic assays were performed to determine the surviving fractions of the cells.
Results:
Biocompatibility tests showed high survival for both cell lines at 5-ALA concentrations of 0.1-100 μg/mL, while AO concentrations above 1 μg/mL significantly reduced survival. Clonogenic assays revealed similar reductions in surviving fractions at 0.5 μg/mL for 5-ALA and AO across both cell lines. A statistically significant decrease in survival at 0.5 μg/mL was observed in PC-3 cells exposed to 2 Gy. Both cell lines were also treated with 100 μg/mL of 5-ALA, a commonly used experimental concentration. This higher concentration resulted in a significant reduction in cell survival compared to 0.5 μg/mL.
Conclusion:
At 0.5 μg/mL, both sensitizers slightly decreased the surviving fraction, with a notable response in the PC3 cells at 2 Gy. At 100 μg/mL, 5-ALA demonstrated a statistically significant decrease in surviving fraction. The limited biocompatibility of AO suggests restrictions as an RDT sensitizer. Ongoing experiments aim to explore cellular uptake and a broader range of photon energies to further compare 5-ALA and AO as RDT sensitizers.