posted on 2022-08-05, 13:20authored byHyeonbin Shin, Seungwon Jeong, Yeongjong Lee, Chanhee Jeon, Gayoung Kwon, Sooyeon Kim, Dongwon Lee
Renal ischemia-reperfusion (IR) injury is an inevitable
complication
in various clinical settings including kidney transplantation and
major vascular surgeries. Renal IR injury is a major risk factor for
acute kidney injury, which still remains a major clinical challenge
without effective therapy. The main cause of renal IR injury is the
massive production of reactive oxygen species (ROS) including hydrogen
peroxide (H2O2) that initiate inflammatory signaling
pathways, leading to renal cell death. In this study, we developed
fucoidan-coated polymeric prodrug (Fu-PVU73) nanoparticles as renal
IR-targeting nanotherapeutics that can rapidly eliminate H2O2 and exert anti-inflammatory and antiapoptotic effects.
Fu-PVU73 nanoparticles were composed of H2O2-activatable antioxidant and anti-inflammatory polymeric prodrug
(PVU73) that incorporated H2O2-responsive peroxalate
linkages, ursodeoxycholic acid (UDCA), and vanillyl alcohol (VA) in
its backbone. Fu-PVU73 nanoparticles rapidly scavenged H2O2 and released UDCA and VA during H2O2-triggered degradation. In the study of renal IR injury mouse
models, Fu-PVU73 nanoparticles preferentially accumulated in the IR
injury-induced kidney and markedly protected the kidney from IR injury
by suppressing the generation of ROS and the expression of proinflammatory
cytokines. We anticipate that Fu-PVU73 nanoparticles have tremendous
therapeutic potential for not only renal IR injury but also various
ROS-associated inflammatory diseases.