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Resolvin D1 delivery to lesional macrophages using antioxidative black phosphorus nanosheets for atherosclerosis
Zhongshan He1, Wei Chen2, Kuan Hu3,4,5
1Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Abstract:
The buildup of plaques in atherosclerosis leads to cardiovascular events, with chronic unresolved inflammation and overproduction of reactive oxygen species (ROS) being major drivers of plaque progression. Nanotherapeutics that can resolve inflammation and scavenge ROS have the potential to treat atherosclerosis. Here we demonstrate the potential of black phosphorus nanosheets (BPNSs) as a therapeutic agent for the treatment of atherosclerosis. BPNSs can effectively scavenge a broad spectrum of ROS and suppress atherosclerosis-associated pro-inflammatory cytokine production in lesional macrophages. We also demonstrate ROS-responsive, targeted-peptide-modified BPNS-based carriers for the delivery of resolvin D1 (an inflammation-resolving lipid mediator) to lesional macrophages, which further boosts the anti-atherosclerotic efficacy. The targeted nanotherapeutics not only reduce plaque areas but also substantially improve plaque stability in high-fat-diet-fed apolipoprotein E-deficient mice. This study presents a therapeutic strategy against atherosclerosis, and highlights the potential of BPNS-based therapeutics to treat other inflammatory diseases.
Insights
Black phosphorus nanosheets (BPNSs) show promise for treating atherosclerosis by reducing inflammation and reactive oxygen species (ROS). Targeted nanotherapeutics using BPNSs further enhance treatment efficacy, improving plaque stability.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cardiovascular Research
Background:
- Atherosclerosis progression is driven by chronic inflammation and reactive oxygen species (ROS).
- Nanotherapeutics offer potential for treating atherosclerosis by targeting inflammation and ROS.
Purpose of the Study:
- To evaluate black phosphorus nanosheets (BPNSs) as a therapeutic agent for atherosclerosis.
- To develop ROS-responsive, targeted nanocarriers for enhanced atherosclerosis treatment.
Main Methods:
- Assessed BPNSs' ability to scavenge ROS and suppress pro-inflammatory cytokines in macrophages.
- Engineered BPNS-based nanocarriers for targeted delivery of resolvin D1.
- Evaluated nanotherapeutic efficacy in high-fat-diet-fed apolipoprotein E-deficient mice.
Main Results:
- BPNSs effectively scavenged ROS and reduced inflammation in lesional macrophages.
- Targeted BPNS nanocarriers delivered resolvin D1, enhancing anti-atherosclerotic effects.
- Nanotherapeutics significantly reduced plaque area and improved plaque stability in vivo.
Conclusions:
- BPNS-based nanotherapeutics represent a viable strategy for treating atherosclerosis.
- This approach holds potential for treating other inflammatory diseases.
