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Macrophage-Targeted ROS-Responsive Nanoplatform for Coordinated NF-κB and Nrf2 Modulation in Atherosclerosis Therapy
Jin Liu1, Bo Li1, Yunlong Tian1
1School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai264005, P.R. China.
This study introduces a novel nanotherapeutic system that precisely targets atherosclerotic plaques. The system releases drugs in response to high reactive oxygen species (ROS) levels, reducing inflammation and plaque progression.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cardiovascular Research
Background:
- Atherosclerosis (AS) involves plaque formation, inflammation, and oxidative stress.
- Current treatments for AS have limitations like restenosis, thrombosis, poor bioavailability, and toxicity.
- There is a critical need for advanced, targeted therapies for atherosclerosis.
Purpose of the Study:
- To develop a multifunctional liposomal platform (Rh-ManLP@Ce) for targeted atherosclerosis intervention.
- To create a system with environment-responsive drug release and active macrophage targeting.
- To investigate the synergistic therapeutic effects of Rhein and Cerium Oxide (CeO2) in AS.
Main Methods:
- Engineered a liposomal platform (Rh-ManLP@Ce) incorporating DSPE-PEG-Rhein and ROS-responsive lipids.
- Decorated the liposome surface with mannose ligands for macrophage targeting.
- Loaded the nanotherapeutic system with Cerium Oxide (CeO2).
- Evaluated in vitro and in vivo performance, including ROS responsiveness, cellular uptake, and therapeutic efficacy.
Main Results:
- Rh-ManLP@Ce demonstrated enhanced responsiveness in high-ROS environments and efficient macrophage internalization.
- Significant accumulation of the nanotherapeutic within atherosclerotic lesions was observed.
- The system effectively inhibited the NF-κB inflammatory pathway via Rhein and activated the Nrf2 antioxidant pathway via CeO2.
- Dual synergistic action suppressed foam cell formation and delayed plaque progression.
Conclusions:
- The developed Rh-ManLP@Ce system offers a precise and effective strategy for managing atherosclerosis.
- This nanotherapeutic platform shows potential for treating diseases associated with oxidative stress and inflammation.
- The study highlights the promise of combining targeted delivery with environment-responsive release for complex diseases.
