Renoprotective Angiographic Polymersomes
Danqing Liu, Erik Jan Cornel, Jianzhong Du
Abstract
Abstract Computed tomography (CT) angiography is powerful for the diagnosis of vascular diseases. Unfortunately, this method usually requires a high dosage of iodinated contrast agents, which can lead to severe elevation of reactive oxygen species (ROS) levels within kidneys. This causes oxidative stress, apoptosis, and hence contrast‐induced nephropathy (CIN), a leading cause of iatrogenic renal failure, especially for patients with renal insufficiency. Herein, a route is shown to circumvent such problems with the usage of rationally designed renoprotective angiographic polymersomes (RAPs) as blood pool CT contrast agents. RAPs are biodegradable nanoparticles prepared via self‐assembly of poly(ethylene oxide)‐ block ‐poly(triiodobenzoic chloride‐conjugated polylysine‐ stat ‐phenylboronic acid pinacol ester‐conjugated polylysine) (PEO 45 ‐ b ‐P[(Lys‐IBC) 45 ‐ stat ‐(Lys‐PAPE) 15 ]). The key to the efficiency of such nanoparticles as renoprotective contrast agents arises from the rationally chosen repeat units: Lys‐IBC exhibits a concentration‐dependent X‐ray attenuation capability and Lys‐PAPE introduces an ROS‐scavenging ability to the polymersome. The study shows that RAPs can reduce the risk of CIN in mice with kidney injury. Additionally, a 5‐fold increase in angiographic live time is observed using RAPs, compared to commonly used iodinated small molecule contrast agents. In summary, a new strategy is proposed for the design of a renoprotective angiographic contrast agent that is capable of reducing the risk of CIN.