A γ-radiation-responsive diselenide-core micelle for on-demand delivery of cannabidiol in the mitigation of acute radiation injury

With the widespread application of nuclear energy, the associated risks of nuclear accidents and radiation leakage have increased considerably. To address potential acute radiation injuries and reduce the toxicity burden posed by conventional radioprotective agents, the development of novel therapeutic strategies is urgently needed. In this study, we designed a γ-radiation-responsive drug delivery system by encapsulating the radioprotective agent cannabidiol (CBD) into amphiphilic polymer micelles (denoted as mPEG-SeSe-St@CBD) incorporating diselenide bonds as radiation-sensitive units. The resulting micelles exhibited a small particle size (≈155 nm), negative surface charge (zeta potential = −14.5 mV), and a stable spherical morphology. In vitro drug release studies demonstrated that the CBD-loaded micelles responded sensitively to low-dose γ-irradiation, achieving over 60% cumulative release within 6 h, with release kinetics governed by Fick diffusion. In vivo evaluations revealed that the polymeric micelles not only promoted body weight recovery in irradiated mice, but also facilitated cellular and tissue uptake, alleviated intracellular oxidative stress, and conferred multi-organ protection. As a result, the 30-day post-irradiation survival rate was enhanced to over 50%. In the absence of radiation, the micelles can remain intact spherical structure, thereby reducing the risk of drug exposure. Collectively, this study presents a radiation-sensitive nanoplatform with radioprotective efficacy, offering a promising new approach for the prevention and treatment of acute radiation injuries.