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.