Nanoparticles reshaping graft-versus-host disease landscape

Graft-versus-host disease (GVHD) is a major immune-mediated complication of allogeneic hematopoietic stem cell transplantation and remains the leading cause of non-relapse mortality. Glucocorticosteroids are the first-line treatment; however, there is a critical need for more effective and less toxic alternatives. Nanomedicine constitutes a promising approach by enabling a more tailored and safer drug delivery, although their use in GVHD remains very scarce. This review aims to systematically analyse the existing literature on nanomaterial-based approaches for the diagnosis, prevention and treatment of GVHD. Encouraging results have been reported across major nanomaterial subtypes, suggesting nanomedicine as a viable and versatile platform to improve GVHD outcomes compared with conventional approaches. However, this review also highlights the heterogeneity and frailty of the available data, and the urgent need for clinical translation and deeper exploration of alternative formulations. Finally, we advance as final remarks innovative encapsulation and targeting rationales, supported by an exploration of novel cellular and molecular mechanisms underlying GVHD, to increase therapeutic efficacy, reduce systemic toxicity, and eventually uncouple GVHD from the beneficial graft-versus-leukemia effect.