Diselenide-based nanoparticles enhancing the radioprotection to the small intestine of mice.

Abstract

The widespread application of ionizing radiation (IR) in medicine, while beneficial, also poses potential risks that necessitate effective countermeasures. Both 2-(3-aminopropylamino) ethanethiol (WR-1065) and curcumin are recognized as radioprotective agents; however, their clinical utility is hindered by notable shortcomings that could be addressed through reactive oxygen species (ROS)-responsive amphiphilic nanomaterials. We introduced a newly synthesized poly (ethylene glycol) (PEG)-polycaprolactone (PCL) polymer integrated with diselenide bonds and curcumin (HOOC-SeSe-Cur-PEG-SeSe-Cur-PCL, PEG-Cur-SeSe-PCL). The resulting spherical nanoparticles (NPs), which self-assembled from this polymer, were uniform with an average diameter of 118 nm. As a carrier for WR-1065, these NPs demonstrated a loading capacity of 30.9% and an efficacy of 56.7%. Importantly, the degradation of WR-1065 within the NPs was minimal in gastric fluid, decreasing by only approximately 20% over a 6-hour period. The innovative aspect of these NPs is their design to destabilize in ROS-rich environments, facilitating the release of WR-1065 and curcumin. Indeed, the survival rate of mice increased to 50% when these NPs were orally administered prior to exposure to a lethal dose of whole-body irradiation (8 Gy). The radioprotective impact of WR-1065-loaded NPs was evident in the small intestine of irradiated mice, characterized by the amelioration of radiation-induced epithelial damage, reduction of DNA damage, and inhibition of the apoptotic pathway. Collectively, this oral nanocarrier system for WR-1065 and curcumin holds promise as a potential candidate for the prophylaxis and treatment of acute intestinal injuries induced by IR.