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一种具有近红外响应性的靶向介孔多巴胺纳米药物平台,用于改善动脉粥样硬化。

A targeting mesoporous dopamine nanodrug platform with NIR responsiveness for atherosclerosis improvement.

机构信息

College of Pharmacy, Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing pharmacodynamic evaluation engineering technology research center, Chongqing 400016, China.

College of Pharmacy, Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing pharmacodynamic evaluation engineering technology research center, Chongqing 400016, China.

出版信息

Biomater Adv. 2022 May;136:212775. doi: 10.1016/j.bioadv.2022.212775. Epub 2022 Mar 24.

DOI:10.1016/j.bioadv.2022.212775
PMID:35929293
Abstract

Atherosclerosis (AS), the formation of plaque lesions in the walls of arteries, causes many mortalities and morbidities worldwide. Currently, achieving site-specific delivery and controlled release at plaques is difficult. Herein, we implemented the strategy of constructing a bionic multifunctional nanoplatform (BM-NP) for targeting and improving plaques. BM-NPs were prepared based on probucol-loaded mesoporous polydopamine (MPDA) carriers and were coated with platelet membranes to impart bionic properties. In vitro experiments confirmed that BM-NPs, which respond to near-infrared (NIR) for drug release, remove reactive oxygen species (ROS), thereby reducing the level of oxidized low-density lipoprotein (ox-LDL) and ultimately helping to inhibit macrophage foaming. In vivo experiments proved that BM-NPs actively accumulated in plaques in the mouse right carotid artery (RCA) ligation model. During treatment, BM-NPs with NIR laser irradiation more effectively reduced the area of plaque deposition and slowed the thickening of the arterial wall intima. More importantly, BM-NPs showed the advantage of inhibiting the increase in triglyceride (TG) content in the body, and good biocompatibility. Hence, our research results indicate that intelligent BM-NPs can be used as a potential nanotherapy to precisely and synergistically improve AS.

摘要

动脉粥样硬化(AS)是动脉壁斑块形成的一种疾病,在全球范围内导致了许多死亡和发病。目前,实现斑块的靶向递药和控制释放仍然具有挑战性。在本研究中,我们构建了一种仿生多功能纳米平台(BM-NP)用于靶向改善斑块。BM-NP 是基于载有普罗布考的介孔聚多巴胺(MPDA)载体构建的,并包被血小板膜以赋予仿生特性。体外实验证实,BM-NP 可响应近红外(NIR)光实现药物释放,同时清除活性氧(ROS),从而降低氧化型低密度脂蛋白(ox-LDL)水平,最终有助于抑制巨噬细胞泡沫化。体内实验证明,BM-NP 在小鼠右侧颈总动脉结扎模型中可主动积累在斑块中。在治疗过程中,接受 NIR 激光照射的 BM-NP 更有效地减少了斑块沉积面积,减缓了动脉壁内膜的增厚。更重要的是,BM-NP 显示出抑制体内甘油三酯(TG)含量增加的优势,且具有良好的生物相容性。因此,我们的研究结果表明,智能 BM-NP 可作为一种潜在的纳米疗法,用于精确协同改善 AS。

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