Targeted echogenic and anti-inflammatory polymeric prodrug nanoparticles for the management of renal ischemia/reperfusion injury.

Ischemia/reperfusion (IR) injury is an inevitable pathological event occurring when blood is resupplied to the tissues after a period of ischemia. One of major causes of IR injury is the overproduction of reactive oxygen species (ROS) including hydrogen peroxide (H 2 O 2), which mediates the expression of various inflammatory cytokines to exacerbate tissue damages. The overproduced H 2 O 2 could therefore serve as a diagnostic and therapeutic biomarker of IR injury. In this study, poly(boronated methacrylate) (pBMA) nanoparticles were developed as nanotheranostic agents for renal IR injury, which not only generate CO 2 bubbles to enhance the ultrasound contrast but also provide potent preventive effects in a H 2 O 2 -triggered manner. The surface of pBMA nanoparticles was decorated with taurodeoxycholic acid (TUDCA) that binds P-selectin overexpressed in inflamed tissues. In the mouse model of renal IR injury, TUDCA-coated pBMA (T-pBMA) nanoparticles preferentially accumulated in the injured kidney and markedly enhanced the ultrasound contrast. T-pBMA nanoparticles also effectively prevented renal IR injury by scavenging H 2 O 2 and suppressing the expression of inflammatory cytokines. Treatment progress of IR injury could be also monitored by echogenic T-pBMA nanoparticles. Given their targeting ability, excellent H 2 O 2 -responsiveness, anti-inflammatory activity and H 2 O 2 -triggered echogenicity, T-pBMA nanoparticles have excellent translational potential for the management of various H 2 O 2 -related diseases including IR injury. [Display omitted] [ABSTRACT FROM AUTHOR]