Efficiency Comparison between Radiotherapy Alone And In The Presence of Radio- or Photo- Sensitizers on Viability of DFW and HT29 Cell Lines: From Simulations to Experimental Results

Introduction: Radiotherapy (RT) is a conventional cancer treatment which address needs of most cancerous patients. However, toxicity of high X-ray energies increases side effects to the normal tissues. Combining RT with agents like radiosensitizers and photosensitizers has improved its effectiveness. This study presents a mathematical model of X-ray induced photodynamic therapy (XPDT) and validates its results with relevant experimental data. Material and Methods: This study developed XPDT using TiO₂ nanoparticles as nanoscintillators and PpIX as a photosensitizer. A multi-scale physicochemical model was created to simulate XPDT, highlighting the role of molecular oxygen in its efficiency. XPDT outcomes were compared with RT—both alone and combined with radiosensitizers—using data from two radioresistant cell lines: DFW and HT-29. Results: Simulations and experimental data showed XPDT to be more effective than RT alone or RT with TiO₂. Simulations estimated XPDT reduced cell viability by 45.28% in DFW and 59.02% in HT-29 compared to RT. Modeling helped estimate both apoptotic and necrotic cell death, and a minimum XPDT efficiency was defined based on cells affected synchronously by both RT and PDT. At 4 Gy irradiation and 4 mg/ml nanocomplex concentration, at least 13.22% of DFW and 21.23% of HT-29 cells were eliminated. TiO₂-enhanced RT had the most effects in cell killing during XPDT. Conclusion: XPDT showed higher efficacy in targeting cancer cells compared to RT or PDT alone. However, further research is needed to understand certain unexpected cellular responses under specific treatment conditions.