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Engineered heart-liver axis nanoregulators synergize autophagy activation and systemic metabolic reprogramming
Yiyong Tang1, Jiadi Liu2, Liya Tian2
1Cardiovascular Ultrasound Department, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Insights
This study introduces a novel nanoplatform that simultaneously targets atherosclerosis and hepatic steatosis. The innovative approach enhances drug delivery and activates cellular mechanisms to combat cardiovascular disease progression.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Nanomedicine
Background:
- Atherosclerosis (AS) is a primary cause of global cardiovascular diseases.
- Current AS treatments are limited as they overlook hepatic steatosis, a related risk factor.
- A synergistic therapeutic strategy targeting both conditions is needed.
Purpose of the Study:
- To develop a smart nanoplatform for synergistic regulation of atherosclerosis and hepatic steatosis.
- To investigate the nanoplatform's efficacy in targeting atherosclerotic plaques and improving drug accumulation.
- To evaluate the nanoplatform's potential in alleviating hepatic steatosis and inhibiting AS progression.
Main Methods:
- Fabrication of a nanoplatform using sulfide iron nanosheets, BMAP-27, and a hybrid biomimetic membrane.
- Utilizing low-intensity focused ultrasound for enhanced local drug accumulation.
- Employing near-infrared laser irradiation to trigger Ca2+ entry via TRPV1 channels.
- Assessing reactive oxygen species (ROS) scavenging, anti-inflammatory effects, and liver-protective capabilities.
Main Results:
- The nanoplatform effectively targeted atherosclerotic plaques and enhanced local drug delivery.
- Near-infrared irradiation induced Ca2+ influx, activating autophagy and cholesterol efflux in foam cells.
- The nanoplatform reduced oxidized low-density lipoprotein, scavenged ROS, and suppressed inflammation.
- Hepatic steatosis was alleviated, plasma triglyceride levels decreased, and AS progression was inhibited.
Conclusions:
- The developed nanoplatform offers a dual-targeting strategy for atherosclerosis and hepatic steatosis.
- This approach demonstrates significant potential for treating cardiovascular diseases by addressing related metabolic disorders.
- The nanoplatform facilitates metabolic reprogramming, providing a promising therapeutic avenue for atherosclerosis.
Abstract:
Atherosclerosis (AS) is the most important pathological basis for cardiovascular diseases worldwide. However, the current mainstream therapeutic strategies for AS only target isolated pathological links, ignoring hepatic steatosis as a related risk factor for AS, which leads to limited effectiveness in controlling the overall course of atherosclerosis. Herein, a smart nanoplatform that can synergistically regulate AS and hepatic steatosis was first reported, which featured sulfide iron nanosheets as the core, grafted with bovine myeloid antimicrobial peptide 27 (BMAP-27), skillfully coated with an erythrocyte-macrophage hybrid biomimetic membrane. First, this nanoplatform is capable of targeting atherosclerotic plaques. When combined with low-intensity focused ultrasound, the nanoplatform markedly enhanced local drug accumulation. The localized temperature rise generated by near-infrared laser irradiation acted to open TRPV1 channels, facilitating Ca2+ entry. This increase in cytosolic Ca2+ activated autophagy in foam cells, upregulated ABCA1-mediated cholesterol efflux, and reduced oxidized low-density lipoprotein accumulation. Meanwhile, FPRM efficiently scavenged reactive oxygen species (ROS) within atherosclerotic plaques and synergized with BMAP-27 to suppress AS-related inflammation. Intriguingly, the classic hepatic accumulation-metabolism pathway of FPRM enabled continuous ROS elimination in the liver, effectively alleviating hepatic steatosis and lowering plasma triglyceride levels, thereby achieving metabolic reprogramming and ultimately inhibiting the progression of atherosclerosis.
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