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A MicroRNA and ROS-Scavenger Co-Loaded Nanogel for in Situ Macrophage Regulation and MR-Visualized Treatment of
Sunli Wan1, Yuanyuan Guo2, Xinhua Liu2
1Department of Radiology, Wuxi No.2 People's Hospital, Jiangnan University Medical Center, 68 Zhongshan Road, Wuxi, Jiangsu, 214002, China.
Abstract:
Atherosclerosis is a major pathophysiological factor in cardiovascular disease and is characterized by inflammatory responses and oxidative stress in plaques. Developing plaque microenvironment regulators for effective atherosclerosis treatment remains a great challenge owing to the pathological complexity, individual heterogeneity, and the limited efficiency of current medications. Herein, the integration of macrophage regulators and reactive oxygen species (ROS) scavengers into a nucleic acid nanogel platform is proposed for a highly efficient visualized treatment of atherosclerosis. As a proof-of-concept, an ROS scavenger with paramagnetic functionality, 2,2,6,6-tetramethylpiperidinyl-1-oxide (TEMPO), is selected for site-specific grafting onto single DNA strands via phosphorothioate groups to obtain TEMPO-DNA conjugates, which are subsequently assembled into TEMPO-grafted Y-shaped blocks with magnetic resonance imaging (MRI) capacity. Additionally, microRNA (miR-146a-5p) with macrophage-reprogramming ability is used as a crosslinker to integrate with the TEMPO-grafted blocks for preparing the multifunctional nanogel. With TEMPO inside, the nanoplatform enabled dynamic monitoring of disease progression and visualization of plaque treatment. The prepared drug co-delivery nanogels significantly relieved oxidative stress and regulated the inflammatory state of macrophages, leading to the remarkable regression and stabilization of plaques. Through its MRI capacity and synergistic therapeutic functionalities, this easy-to-prepare nanogel system provides a promising alternative strategy for imaging and visualizing the treatment of atherosclerotic plaques.
Insights
This study introduces a novel nanogel platform that combines macrophage regulation and reactive oxygen species (ROS) scavenging for atherosclerosis treatment. The nanogel enables visualized plaque monitoring and therapeutic intervention, offering a promising approach for cardiovascular disease management.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cardiovascular Research
Background:
- Atherosclerosis involves complex plaque microenvironments with inflammation and oxidative stress.
- Current treatments face challenges due to pathological complexity and limited efficacy.
- Need for advanced therapeutic strategies to regulate plaque microenvironment and visualize treatment.
Purpose of the Study:
- To develop a multifunctional nanogel platform for visualized atherosclerosis treatment.
- To integrate macrophage regulators and reactive oxygen species (ROS) scavengers into a single nanoplatform.
- To enable dynamic monitoring and therapeutic intervention in atherosclerotic plaques.
Main Methods:
- Synthesized TEMPO-DNA conjugates for ROS scavenging and MRI capability.
- Utilized miR-146a-5p as a crosslinker to form multifunctional nanogels.
- Evaluated nanogel efficacy in relieving oxidative stress and regulating macrophage inflammation.
Main Results:
- The nanogel platform demonstrated dynamic monitoring and visualization of plaque treatment.
- Successfully relieved oxidative stress and modulated macrophage inflammatory states.
- Achieved significant regression and stabilization of atherosclerotic plaques.
Conclusions:
- The developed nanogel system offers a promising strategy for imaging and visualizing atherosclerosis treatment.
- Combines synergistic therapeutic functionalities with magnetic resonance imaging (MRI) capacity.
- Provides an easy-to-prepare and effective alternative for managing atherosclerotic plaques.
