Interleukin-12 sustained release system promotes hematopoietic recovery after radiation injury

The continuous production of all mature blood cell lineages is maintained by Hematopoietic stem cells (HSCs), but they are highly susceptible to damage by ionizing radiation (IR) that induces death. Therefore, devising the therapeutic strategies that can mitigate hematopoietic toxicity caused by IR would benefit acute radiation syndrome (ARS) victims and radiation therapy patients. Here, we prepared an injectable hydrogel based on RGD-alginate and Laponite by a simple mixing method to release IL-12 (RGD-Alg/Laponite@IL-12) slowly and locally. The localization administration of RGD-Alg/Laponite@IL-12 substantially increased the survival and promoted the hematopoietic recovery of mice following sublethal-dose irradiation. These results suggested that local intra-bone marrow injection of RGD-Alg/Laponite@IL-12 hydrogel can effectively stimulate IL12R-PI3K/AKT signaling axis, which promotes proliferation and hematopoietic growth factors (HGFs) secretion of bone marrow mesenchymal stem/stromal cells (BM-MSCs). This signaling axis facilitates hematopoietic microenvironment repair and plays a pivotal role in hematopoietic reconstitution. In conclusion, our study attempted a biomaterial-sustained release of IL-12 for the treatment of irradiated hematopoietic injury and provided a new therapeutic strategy for hematopoietic acute radiation syndrome (H-ARS).