Abstract Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a highly effective treatment for a variety of hematologic malignancies, but also associated with serious complications, such as graft-versus-host-disease (GVHD), a severe immune condition that manifests in multiple organs including the kidneys. Kidney injury in the setting of allo-HSCT has an incidence as high as 80% and leads to high patient morbidity and mortality, however, its progression and mechanisms remain poorly characterized. Moreover, no approved drugs for AKI of any etiology exist, as most experimental therapies have poor pharmacokinetic profiles and minimal efficacy in treating AKI in humans. We have characterized the pathology, genetic and molecular signatures of GVHD-mediated AKI in a murine model of HCT. GVHD results in AKI characterized predominantly by T-cell infiltration and activation of inflammatory pathways in both donor infiltrating inflammatory cells, as well as resident cells (i.e. tubules). By RNA sequencing, we have identified specific inflammatory pathways that are differentially expressed between healthy and GVHD mice and can serve as targets for therapeutic intervention. Moreover, we have synthesized nanoparticles that can specifically target proteins overexpressed in GVHD-kidneys and can encapsulate a variety of small molecule drugs. The complete understanding of this disease and development of this technology has a high potential to improve clinical practice and patient prognosis after allo-HCT, but it can also serve as a platform for treating other forms of cancer-associated kidney injury (e.g. induced by nephrotoxic chemotherapy), thus affecting the life of numerous patients. Citation Format: Magdalini Panagiotakopoulou, Emma Grabarnik, Edgar A. Jaimes, Marcel R. van den Brink, Daniel A. Heller. Acute kidney injury induced by allogeneic hematopoietic stem cell transplantation: disease understanding and treatment with nanotechnology-based therapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 501.