Microbubble Functionalization with Platelet Membrane Enables Targeting and Early Detection of Sepsis-Induced Acute Kidney Injury.

Abstract

The morbidity and mortality of sepsis-induced acute kidney injury (SAKI) remain high. Early detection using molecular ultrasound imaging may reduce mortality and improve the prognosis. Inspired by the intrinsic relationship between platelets and SAKI, platelet membrane-coated hybrid microbubbles (Pla-MBs) are designed for early recognition of SAKI. Pla-MBs are prepared by ultrasound-assisted recombination of liposomes and platelets, consisting of inherent platelet membrane isolated from platelets. By coating with platelet membranes, Pla-MBs are endowed with various adhesive receptors (such as integrin αIIbβ3), providing a benefit for selective adhesion to damaged endothelium in SAKI. In a rat SAKI model, by combining the advantages of molecular ultrasound imaging and platelet membrane, Pla-MBs display platelet-mimicking properties and achieve the early targeted diagnosis of SAKI prior to the regular laboratory markers of kidney function. Moreover, the expression of platelet-binding proteins (von Willebrand factor and fibrinogen) in the kidneys shows consistent results with molecular ultrasound imaging. Together, microbubble functionalization with platelet membranes is diagnostically beneficial for SAKI and might be a promising modality for endothelial injury diseases in the future.