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用于解决动脉粥样硬化炎症的促消退脂质介质的仿生纳米载体

Biomimetic Nanocarriers of Pro-Resolving Lipid Mediators for Resolution of Inflammation in Atherosclerosis.

作者信息

Anghelache Maria, Voicu Geanina, Deleanu Mariana, Turtoi Mihaela, Safciuc Florentina, Anton Ruxandra, Boteanu Delia, Fenyo Ioana Madalina, Manduteanu Ileana, Simionescu Maya, Calin Manuela

机构信息

Medical and Pharmaceutical Bionanotechnologies Laboratory, Institute of Cellular Biology and Pathology "Nicolae Simionescu", Romanian Academy, Bucharest, 050568, Romania.

Liquid and Gas Chromatography Laboratory, Institute of Cellular Biology and Pathology "Nicolae Simionescu", Romanian Academy, Bucharest, 050568, Romania.

出版信息

Adv Healthc Mater. 2024 Jan;13(3):e2302238. doi: 10.1002/adhm.202302238. Epub 2023 Nov 8.

DOI:10.1002/adhm.202302238
PMID:37852632
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11469162/
Abstract

Atherosclerosis (ATH) is a systemic disease characterized by a chronic inflammatory process and lipid deposition in the arterial walls. The chronic inflammation within ATH lesions results, at least in part, from the failed resolution of inflammation. This process is controlled actively by specialized pro-resolving lipid mediators (SPMs), namely lipoxins, resolvins, protectins, and maresins. Herein, biomimetic nanocarriers are produced comprising a cocktail of SPMs-loaded lipid nanoemulsions (LN) covered with macrophage membranes (Bio-LN/SPMs). Bio-LN/SPMs retain on their surface the macrophage receptors involved in cellular interactions and the "marker of self" CD47, which impede their recognition and uptake by other macrophages. The binding of Bio-LN/SPMs to the surface of endothelial cells (EC) and smooth muscle cells (SMC) is facilitated by the receptors on the macrophage membranes and partly by SPMs receptors. In addition, Bio-LN/SPMs prove functional by reducing monocyte adhesion and transmigration to/through activated EC and by stimulating macrophage phagocytic activity. After intravenous administration, Bio-LN/SPMs accumulate in the aorta of ApoE-deficient mice at the level of atherosclerotic lesions. Also, the safety assessment testing reveals no side effects or immunotoxicity of Bio-LN/SPMs. Thus, the newly developed Bio-LN/SPMs represent a reliable targeted nanomedicine for the resolution of inflammation in atherosclerosis.

摘要

动脉粥样硬化（ATH）是一种全身性疾病，其特征为慢性炎症过程和脂质在动脉壁中的沉积。ATH病变内的慢性炎症至少部分是由于炎症未能得到有效消退所致。这一过程由专门的促消退脂质介质（SPM）积极调控，即脂氧素、消退素、保护素和maresin。在此，制备了仿生纳米载体，其由负载有SPM的脂质纳米乳剂（LN）混合物组成，并覆盖有巨噬细胞膜（Bio-LN/SPMs）。Bio-LN/SPMs在其表面保留了参与细胞相互作用的巨噬细胞受体以及“自身标记物”CD47，这阻碍了它们被其他巨噬细胞识别和摄取。巨噬细胞膜上的受体以及部分SPM受体促进了Bio-LN/SPMs与内皮细胞（EC）和平滑肌细胞（SMC）表面的结合。此外，Bio-LN/SPMs通过减少单核细胞对活化EC的黏附和向/穿过活化EC的迁移以及刺激巨噬细胞吞噬活性而发挥功能。静脉注射后，Bio-LN/SPMs在载脂蛋白E缺陷小鼠主动脉的动脉粥样硬化病变部位积聚。而且，安全性评估测试显示Bio-LN/SPMs没有副作用或免疫毒性。因此，新开发的Bio-LN/SPMs代表了一种用于解决动脉粥样硬化炎症的可靠靶向纳米药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae86/11469162/6844e8f40bd0/ADHM-13-2302238-g008.jpg
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