Autologous platelet delivery of siRNAs by autologous plasma protein self-assembled nanoparticles for the treatment of acute kidney injury

Acute kidney injury (AKI) involves the activation of intrarenal hemostatic and inflammatory pathways. Platelets rapidly migrate to affected sites of AKI and release extracellular vesicles (EVs) laden with bioactive mediators that regulate inflammation and hemostasis. While small interfering RNA (siRNA) is a potent gene-silencing tool for biomedical applications, its therapeutic application in vivo remains challenging. We developed an innovative nucleic acid delivery platform by hybridizing synthetic transformation-related protein 53 (p53) siRNA with autologous plasma and incubating the complex with autologous platelets. These engineered platelets selectively delivered p53 siRNA to injured renal tubular cells via EV-mediated cargo release, resulting in targeted p53 suppression in renal cells and subsequent attenuation of AKI progression. This platelet-centric translational strategy demonstrates significant potential for advancing precision therapies in AKI by exploiting endogenous platelet trafficking to deliver therapeutics directly to injury sites.Supplementary Information The online version contains supplementary material available at 10.1186/s12951-025-03338-6.