RESUMO
Atherosclerosis (AS) is a significant contributor to cardiovascular events. Advanced AS is particularly concerning, as it leads to the formation of high-risk vulnerable plaques. Current treatments for AS focus on antithrombotic and lipid-lowering interventions, which are effective in treating early-stage AS. Recent studies have shown that macrophage polarization plays a crucial role in the development of AS. This study presents a new biomedical application of natural tannic acid as an anti-inflammatory nanoplatform for advanced AS. Tannic acid-poloxamer nanoparticles (TPNP) are fabricated through self-assembly of tannic acid (TA) and poloxamer. TPNP has the potential to provide effective treatment for advanced AS. According to in vitro studies, TPNP has been found to suppress the inflammatory response in lipopolysaccharide-stimulated macrophages by scavenging reactive oxygen species (ROS), downregulating the expression levels of inflammatory cytokines (such as interleukin-10 and tumor necrosis factor-α) and regulating polarization of macrophages. In vivo studies further reveal that TPNP can retard the development of advanced atherosclerotic plaques by reducing ROS production and promoting M2 macrophage polarization in the aorta of ApoE-/- mice. Overall, these findings suggest that TPNP could be used to develop natural multifunctional nanoplatforms for molecular therapy of AS and other inflammation-related diseases.
RESUMO
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 via in vivo 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 via the in vivo treatment studies. As such, our data highlight LP@ZIF-8 as a promising therapeutic agent capable of attenuating the severity of AS.
