Highly efficient in vivo uranium clearance achieved by carboxyl functionalized nanocages

Abstract

Effective in vivo uranium clearance and mitigation of its radiation damage are crucial for the safety of uranium-exposed workers and residents, yet remain challenging. Current small-molecule drugs suffer from rapid metabolism and poor organ targeting, limiting their effectiveness in both preventive and long-term exposure scenarios. Nano decorporation agents, despite their prolonged in vivo retention due to nanoscale size and physico-chemical properties, encounter limitations such as restricted long channels and mismatched coordination geometry of chelating sites, which impede rapid and selective uranyl binding under physiological conditions. This study employs discrete metal-organic polyhedra (MOPs) to achieve a dense grafting and flexible arrangement of carboxylic acid chains, aiming to attain collaborative coordination of uranyl ions on the faces of tetrahedral structures. These MOPs selectively capture uranyl at low concentrations in vitro and show superior in vivo removal efficiency compared to clinical drugs and currently reported nano agents in both prophylactic and delayed treatments, where higher grafting density of carboxyl chains leads to greater decorporation efficiency. This work underscores the potential of MOPs in advancing nanomedicine for nuclear emergencies.