Sequential Treatment of Cell Cycle Regulator and Nanoradiosensitizer Achieves Enhanced Radiotherapeutic Outcome

Nanoradiosensitizers are promising agents for enhancing cancer radiotherapeutic efficiency. Although many attempts have been adopted to improve their radiation enhancement effect through regulation of their size, shape, and/or surface chemistry, few methods have achieved satisfactory radiotherapeutic outcomes. Herein, we propose a sequential drug treatment strategy through cell cycle regulation for achieving improved radiotherapeutic performance of the nanoradiosensitizers. Docetaxel (DTX), a clinically approved first-line drug in breast cancer treatment, is first used to affect the cell cycle distribution and arrest cells in the G2/M phase, which has been proven to be the most effective phase for endocytosis and the most radiosensitive phase for radiotherapy. The cells are then exposed to a commonly used nanoradiosensitizer, gold nanoparticles (GNPs), followed by X-ray irradiation. It is found that by arresting the cancer cells in G2/M phase via the DTX pretreatment, the cellular internalization of GNPs is significantly promoted, therefore enhancing the radiosensitivity of cancer cells. The sensitization enhancement ratio of this sequential DTX/GNP treatment reaches 1.91, which is significantly higher than that (1.29) of GNP treatment. Considering its low cost, simple design, and high feasibility, this sequential drug delivery strategy may hold great potential in radiotherapy.