Abstract
BackgroundAs one typical cardiovascular disease, atherosclerosis severely endanger people’ life and cause burden to people health and mentality. It has been extensively accepted that oxidative stress and inflammation closely correlate with the evolution of atherosclerotic plaques, and they directly participate in all stages of atherosclerosis. Regarding this, anti-oxidation or anti-inflammation drugs were developed to enable anti-oxidative therapy and anti-inflammation therapy against atherosclerosis. However, current drugs failed to meet clinical demands.MethodsNanomedicine and nanotechnology hold great potential in addressing the issue. In this report, we engineered a simvastatin (Sim)-loaded theranostic agent based on porous manganese-substituted prussian blue (PMPB) analogues. The biomimetic PMPB carrier could scavenge ROS and mitigate inflammation in vitro and in vivo. Especially after combining with Sim, the composite Sim@PMPB NC was expected to regulate the processes of atherosclerosis. As well, Mn2+ release from PMPB was expected to enhance MRI.ResultsThe composite Sim@PMPB NC performed the best in regulating the hallmarks of atherosclerosis with above twofold decreases, typically such as oxidative stress, macrophage infiltration, plaque density, LDL internalization, fibrous cap thickness and foam cell birth, etc. Moreover, H2O2-induced Mn2+ release from PMPB NC in atherosclerotic inflammation could enhance MRI for visualizing plaques. Moreover, Sim@PMPB exhibited high biocompatibility according to references and experimental results.ConclusionsThe biomimetic Sim@PMPB theranostic agent successfully stabilized atherosclerotic plaques and alleviated atherosclerosis, and also localized and magnified atherosclerosis, which enabled the monitoring of H2O2-associated atherosclerosis evolution after treatment. As well, Sim@PMPB was biocompatible, thus holding great potential in clinical translation for treating atherosclerosis.Graphic abstract
Highlights
Cardiovascular diseases are highly prevalent and cause the most deaths across the whole world, approximately accounting for nearly half of all deaths [1]
The biomimetic Sim@porous manganese-substituted prussian blue (PMPB) theranostic agent successfully stabilized atherosclerotic plaques and alleviated atherosclerosis, and localized and magnified atherosclerosis, which enabled the monitoring of H2O2-associated atherosclerosis evolution after treatment
Synthesis of biomimetic PMPB and Sim@PMPB NC The synthetic procedures of PMPB NC were shown in Fig. 1a, and they were obtained according to a classic reference [24]
Summary
Cardiovascular diseases are highly prevalent and cause the most deaths across the whole world, approximately accounting for nearly half of all deaths [1]. Starting from endothelial layer dysfunction, atherosclerotic plaques as the hallmark of atherosclerosis are progressively evolved over time In this evolution process, some typically pathological characteristics were concurrently discerned in the intimal layer, e.g., oxidized lowdensity lipoproteins (LDL) accumulation, systematic and local inflammation, oxidative stress augmentation, macrophage infiltrations, collagen-rich fibrous cap development and foam cell birth, etc. The oxidized LDL is accumulated in the intimal layer to promote local inflammation, which further induces a series of structural and physiological changes [7, 11, 15] Based on this fact, inflammation and oxidative stress that have been regarded as the hallmarkers of atherosclerosis can serve as the targets to stimulate the development of various therapeutic drugs and predict cardiovascular events with acute coronary syndromes [15,16,17].
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