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.