Photosensitizer-Enhanced Radiotherapy Reduces Giant Cancer Cell Formation in HeLa and A431 Models

Giant cancer cells are abnormal tumor cells that often arise after ionizing radiation (IR) treatment. Their persistence is associated with tumor resistance, recurrence, and poor clinical outcomes, highlighting the need for strategies that can eliminate them effectively. Radiotherapy (RT), which uses IR to damage tumor DNA, remains an indispensable method of choice in cancer therapy. Photodynamic therapy (PDT), by contrast, involves a photosensitizing drug and light activation to produce reactive oxygen species (ROS) that destroy cancer cells. Importantly, photosensitizers may also act as radiosensitizers, making them promising candidates for combination therapy.

In our study, we tested whether combining PDT and RT could improve cancer cell killing and reduce giant cell formation. HeLa (cervical carcinoma) and A431 (epidermoid carcinoma) cells were treated with Photosens (NIOPIK, Russia), followed by light exposure at 20 J/cm². IR was delivered using a Novalis TX electron accelerator at 600 Gy/hour, with doses guided by the LD50 for both HeLa and A431 cancer cell line (6 Gy).

The combined treatment showed a strong cytotoxic effect and, importantly, caused a marked reduction in the proportion of giant cancer cells formed compared to IR alone. Our results suggest that combining PDT with RT provides a dual attack strategy that not only improves tumor cell killing but also reduces the formation of giant cells, which may translate into more effective and durable cancer control in clinical practice.

The study was supported by the Ministry of Education and Science of the Russian Federation (State assignment FSWR-2023-0032).