Supramolecular Nano-Assembly of Caffeate-Strengthened Phenylboronic Ester with Multistep ROS Scavenging Ability for Targeted Therapy of Acute Kidney Injury

Acute kidney injury (AKI) is a life-threatening complication with a considerable occurrence among patients. AKI is typically accompanied by an elevation in reactive oxidative species (ROS) in renal tissues, which is the main contributor to kidney damage. Herein, a supramolecular nano-assembly (Ser-HPEC) containing an ethyl caffeate-strengthened phenylboronic ester with ROS-triggered antioxidative ability is proposed for AKI-targeted therapy. Nano-assemblies can rapidly accumulate in the ischemia-reperfusion-injured kidney via kidney injury molecule-1 (Kim-1)-mediated homing ability of l-serine. By consuming pathological levels of ROS, two different antioxidants, ethyl caffeate and 4-hydroxybenzyl alcohol, are spontaneously released from a single module to relieve oxidative stress and diminish acute inflammation in injured renal tissue. The multistep ROS scavenging strategy combined with a precise targeting capability endows the aforementioned nano-assembly with effectiveness in preserving the integrity and functions of the injured kidney, providing new inspiration for the treatment of inflammatory diseases, including AKI. Homing, responding, and more antioxidants-three musketeers to eliminate reactive oxidative species (ROS): A triplet anti-ROS nanocarrier made of ethyl caffeate modified phenylboronic acid is applied to mitigate ischemia-reperfusion induced acute kidney injury with an enhanced precision assisted by Kim-1-targeting l-serine.image