Monitoring Nitric Oxide-Induced Hypoxic Tumor Radiosensitization by Radiation-Activated Nanoagents under BOLD/DWI Imaging.

Tumor heterogeneity leads to unpredictable radiotherapeutic outcomes although multiple sensitization strategies have been developed. Real-time monitoring of treatment response through noninvasive imaging methods is critical and a great challenge in optimizing radiotherapy. Herein, we propose a combined functional magnetic resonance imaging approach (blood-oxygen-level-dependent/diffusion-weighted (BOLD/DWI) imaging) for monitoring tumor response to nitric oxide (NO)-induced hypoxic radiosensitization achieved by radiation-activated nanoagents (NSC@SiO2-SNO NPs). This nanoagent carrying NO donors can efficiently concentrate in tumors and specifically produce high concentrations of NO under radiation. In vitro and in vivo studies show that this nanoagent can effectively reduce tumor hypoxia, promote radiation-induced apoptosis and DNA damage under hypoxia, and ultimately inhibit tumor growth. In vivo BOLD/DWI imaging enables noninvasive monitoring of improvements in tumor oxygen levels and radiosensitivity during treatment with this nanostrategy by quantifying functional parameters. This work demonstrates that BOLD/DWI imaging is a useful tool for evaluating tumor response and monitoring the effectiveness of radiotherapeutic strategies aimed at improving hypoxia, with great clinical potential.