Dynamically-enhanced retention of gold nanoclusters in HeLa cells following X-rays exposure: A cell cycle phase-dependent targeting approach

Abstract

Background and purpose: Cell cycle phase could affect the cellular uptake of nanoparticles. Based on the fact that ionizing radiation exposure can delay cell cycle progression including inducing G2/M phase arrest, we propose that ionizing radiation exposure is a cell cycle phase-dependent targeting approach for intracellular delivery of nano-agents in tumor cells.

Materials and methods: We synthesized luminescent gold nanoclusters (AuNCs) using a one-pot green synthetic method. Subsequently, we used the as-prepared AuNCs as both "nano-agents" and fluorescent trafficking probes for our study using human cervical carcinoma HeLa cells. Estimating the cellular uptake of AuNCs and cell cycle analysis were performed following X-rays irradiation and cell synchronization.

Results: Our work showed that X-rays irradiation could delay the division of HeLa cells and thereby enhance the retention of AuNCs in HeLa cells, which is a reverse strategy compared with other studies on synergistic nano-radiotherapy. Our results demonstrated that the cell cycle synchronization influenced the cellular uptake processes of AuNCs, suggesting that dynamic cell cycle progression could affect the cellular uptake kinetics of AuNCs.

Conclusion: We consider that the radiation-induced cell division delay might provide a possible mechanism underlying the enhanced effect for the cellular uptake of AuNCs in irradiated HeLa cells.

Keywords: Cell cycle; Cellular uptake; Ionizing radiation; Nano-agents; Synergistic chemo-radiotherapy.