仿生普鲁士蓝类似物实现的活性氧清除和炎症减轻可抑制动脉粥样硬化。
Reactive oxygen species scavenging and inflammation mitigation enabled by biomimetic prussian blue analogues boycott atherosclerosis.
作者信息
Zhang Yan, Yin Yifei, Zhang Wei, Li Hongyan, Wang Taixia, Yin Haohao, Sun Liping, Su Chunxia, Zhang Kun, Xu Huixiong
机构信息
Department 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.
Department of Radiology, Affiliated Hospital of Guilin Medical University, No. 15 Le-Qun Road, Xiufeng District, Guilin, 541001, Guangxi, People's Republic of China.
出版信息
J Nanobiotechnology. 2021 May 31;19(1):161. doi: 10.1186/s12951-021-00897-2.
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, Mn 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, HO-induced Mn 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 HO-associated atherosclerosis evolution after treatment. As well, Sim@PMPB was biocompatible, thus holding great potential in clinical translation for treating atherosclerosis.
背景
动脉粥样硬化作为一种典型的心血管疾病，严重危及人们的生命，给人们的健康和心理带来负担。氧化应激和炎症与动脉粥样硬化斑块的发展密切相关，并直接参与动脉粥样硬化的各个阶段，这一点已被广泛接受。鉴于此，人们开发了抗氧化或抗炎药物来进行针对动脉粥样硬化的抗氧化治疗和抗炎治疗。然而，目前的药物未能满足临床需求。
方法
纳米医学和纳米技术在解决这一问题方面具有巨大潜力。在本报告中，我们基于多孔锰取代普鲁士蓝（PMPB）类似物设计了一种负载辛伐他汀（Sim）的诊疗剂。这种仿生PMPB载体能够在体外和体内清除活性氧并减轻炎症。特别是与Sim结合后，复合Sim@PMPB纳米粒有望调节动脉粥样硬化的进程。此外，预计PMPB释放的锰会增强磁共振成像（MRI）。
结果
复合Sim@PMPB纳米粒在调节动脉粥样硬化特征方面表现最佳，相关指标降低了两倍以上，典型的如氧化应激、巨噬细胞浸润、斑块密度、低密度脂蛋白内化、纤维帽厚度和泡沫细胞生成等。此外，在动脉粥样硬化炎症中，过氧化氢诱导PMPB纳米粒释放锰，可增强MRI以实现斑块可视化。而且，根据参考文献和实验结果，Sim@PMPB表现出高生物相容性。
结论
仿生Sim@PMPB诊疗剂成功稳定了动脉粥样硬化斑块并减轻了动脉粥样硬化，同时对动脉粥样硬化进行了定位和放大，从而能够监测治疗后与过氧化氢相关的动脉粥样硬化演变。此外，Sim@PMPB具有生物相容性因此在治疗动脉粥样硬化的临床转化中具有巨大潜力。
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