Organic-inorganic covalent selenium reversing ischemic reperfusion injury

Clear elucidation of the connection between chemical structure and biological action mechanisms is the key issue preventing the successful development of nanomedicines. Herein, employing essential trace element selenium (Se) as an example, we fabricate organic-inorganic covalent Se hybrid by anchoring Se atom to polyethylene glycol chain during carbonization to form organic Se-C and inorganic Se-Se bonds in one system to integrate the advantages of both species. The weak covalent Se-Se bond breaks down in response to redox stimuli, thus releases organic Se with stronger electron transfer ability to scavenge free radicals, and forms highly active inorganic Se, which further releases free Se atom to trigger selenoprotein synthesis and activation, ultimately reverses reperfusion injury in male-mice ischemic stroke, and improves neurological restoration. This work provides a unique Se atom reprogramming strategy to design highly bioactive hybrid Se species with clear chemical nature and action mechanisms. Developing potent and biocompatible antioxidative nanomedicines is beneficial for reversing ischemic reperfusion injury, but hindered by a lack of understanding of biological action mechanisms. Here, the authors report bioactive organic-inorganic covalent selenium hybrid nanoparticles, and elucidate their mechanisms of action in suppressing reperfusion-induced injury of ischemic stroke.