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Reactive oxygen species scavenging and inflammation mitigation enabled by biomimetic prussian blue analogues boycott
Yan Zhang1, Yifei Yin1, Wei Zhang2
1Department of Medical Ultrasound and Central Laboratory, Shanghai Tenth People's Hospital, Ultrasound Research and Education Institute, Clinical Research Center for Interventional Medicine, Tongji University School of Medicine, Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment, National Clinical Research Center for Interventional Medicine, No. 301 Yan-chang-zhong Road, Shanghai, 200072, People's Republic of China.
Insights
A novel simvastatin-loaded theranostic agent (Sim@PMPB NC) effectively stabilized atherosclerotic plaques by reducing oxidative stress and inflammation. This nanomedicine also enabled enhanced MRI visualization for monitoring disease progression.
Area of Science:
- Nanomedicine and materials science
- Cardiovascular disease research
- Biomedical imaging
Background:
- Atherosclerosis is a major cardiovascular disease driven by oxidative stress and inflammation.
- Current anti-atherosclerosis therapies face limitations in meeting clinical demands.
- Nanotechnology offers promising solutions for advanced atherosclerosis treatment.
Purpose of the Study:
- To engineer a simvastatin-loaded theranostic agent for atherosclerosis treatment and monitoring.
- To evaluate the anti-atherosclerotic efficacy of the novel agent in vitro and in vivo.
- To assess the potential of the agent for enhanced magnetic resonance imaging (MRI) of atherosclerotic plaques.
Main Methods:
- Development of porous manganese-substituted prussian blue (PMPB) analogues as a nanocarrier.
- Loading of simvastatin (Sim) onto PMPB to create Sim@PMPB nanocomposites (NC).
- In vitro and in vivo evaluation of ROS scavenging, inflammation mitigation, and anti-atherosclerotic effects.
- Assessment of Mn2+ release for MRI enhancement in the presence of H2O2.
Main Results:
- Sim@PMPB NC significantly reduced key atherosclerosis hallmarks, including oxidative stress, macrophage infiltration, and plaque density.
- The agent demonstrated effective stabilization of atherosclerotic plaques and reduced foam cell formation.
- H2O2-triggered Mn2+ release from Sim@PMPB NC enhanced MRI visualization of plaques in inflammatory conditions.
- Sim@PMPB exhibited excellent biocompatibility in experimental models.
Conclusions:
- The biomimetic Sim@PMPB theranostic agent shows significant potential for stabilizing atherosclerotic plaques and alleviating atherosclerosis.
- This nanomedicine enables localized monitoring of atherosclerosis evolution via MRI, particularly in response to H2O2.
- The high biocompatibility of Sim@PMPB suggests promising prospects for clinical translation in treating atherosclerosis.
Background:
As 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.
Methods:
Nanomedicine 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.
Results:
The 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.
Conclusions:
The 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.
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