Supramolecular Nano-Assembly of Caffeate-Strengthened Phenylboronic Ester with Multistep ROS Scavenging Ability for
Fan Jia1,2, Bo Yu1, Jian Li1,2
1MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang Province, 310027, P. R. China.
Abstract:
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.
Insights
This study introduces a novel nano-assembly for acute kidney injury (AKI) therapy. The nano-assembly targets injured kidneys, releases antioxidants to combat oxidative stress, and preserves kidney function.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Renal Medicine
Background:
- Acute kidney injury (AKI) is a critical condition often caused by increased reactive oxidative species (ROS) in renal tissues.
- Oxidative stress and inflammation are key contributors to kidney damage in AKI.
Purpose of the Study:
- To develop a supramolecular nano-assembly (Ser-HPEC) for targeted AKI therapy.
- To utilize ROS-triggered antioxidant release for mitigating kidney damage.
Main Methods:
- Fabrication of a supramolecular nano-assembly (Ser-HPEC) with phenylboronic ester and ethyl caffeate.
- Incorporation of l-serine for kidney injury molecule-1 (Kim-1)-mediated homing to injured kidneys.
- In vivo evaluation of nano-assembly efficacy in an ischemia-reperfusion injury model.
Main Results:
- The Ser-HPEC nano-assembly demonstrated rapid accumulation in ischemia-reperfusion-injured kidneys.
- Spontaneous release of ethyl caffeate and 4-hydroxybenzyl alcohol upon encountering ROS.
- Effective reduction of oxidative stress and acute inflammation in renal tissues.
- Preservation of kidney integrity and function.
Conclusions:
- The developed nano-assembly offers a targeted and effective therapeutic strategy for AKI.
- The ROS-scavenging and targeted delivery approach shows promise for treating inflammatory kidney diseases.
- This work provides new insights into nanomedicine applications for AKI treatment.
