Atherosclerosis (AS) is a condition associated with dysfunctional lipid metabolism and an inflammatory immune microenvironment that remains the leading cause of severe cardiovascular events. Drugs exhibiting both anti-inflammatory and lipid-scavenging activity hold great promise for treating AS. In this study, zeolitic imidazolate framework-8 (ZIF-8) nanoparticles loaded with losartan potassium (LP) were developed as an anti-AS treatment to target both of these therapeutic arms simultaneously. LP@ZIF-8 accumulated within AS target tissues via the enhanced permeability and retention (EPR) effect, as confirmed near-infrared fluorescence (NIRF) imaging and was disrupted in response to the low pH. ZIF-8 could activate autophagy, thus regulating lipid metabolism and restoring cholesterol homeostasis as previously reported, while the released LP served as an anti-inflammatory angiotensin receptor blocker (ARB) inhibitor, which was confirmed the treatment studies. As such, our data highlight LP@ZIF-8 as a promising therapeutic agent capable of attenuating the severity of AS.
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