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

Abstract

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.

Biomarker-driven molecular imaging probes in radiotherapy

“…Taken together, conventional fMRI scanning approaches and other quantitative imaging modalities have already been used to monitor the biological response in the tumor during the treatment procedure for external/internal radiotherapy 125 , 154 . These quantitative imaging modalities also lay a solid foundation for developing biomarkers-driven molecular imaging with specificity and accuracy.…”

Development of nanotechnology-mediated precision radiotherapy for anti-metastasis and radioprotection

“…[33][34][35] Moreover, specific imaging techniques can be used to monitor the TME and tumor responses to therapy, thus beneficial in guiding precision RT. [36][37][38] Furthermore, the exo/endogenous stimuli responsive-nanotechnologies also play an important role in realizing precision RT. For instance, pH-responsive nanoradiosensitizers are able to self-regulate their particle sizes at different pH values for enhanced tumor penetration.…”

“…20a). 36 The NaGdF 4 :Eu 3+ NPs were coated with a mesoporous silica layer and then loaded with S-nitrosothiol (SNO, a nitric oxide (NO) donor) (NSC@SiO 2 -SNO). NSC@SiO 2 -SNO could release a great deal of NO upon X-ray irradiation.…”

“…761 The BOLD/DWI fMRI was used to monitor tumor radiosensitivity and oxygen concentration. 36 Liu et al developed a quantitative MRI-based diagnostic system to predict tumors’ responses to RT. The system could stratify pancreatic patients into resistant and sensitive groups.…”