Selenopeptide nanomedicine ameliorates atherosclerosis by reducing monocyte adhesions and inflammations

作者全名："Luo, Zhen; Jiang, Yuxing; Liu, Zimo; Guo, Lamei; Zhang, Li; Rong, Hongtao; Duan, Zhongyu; Liang, Hongwen; Zhang, Aili; Wang, Lei; Yi, Yu; Wang, Hao"

作者地址："[Luo, Zhen; Jiang, Yuxing; Liu, Zimo; Guo, Lamei; Zhang, Li; Wang, Lei; Yi, Yu; Wang, Hao] Natl Ctr Nanosci & Technol NCNST, CAS Ctr Excellence Nanosci, CAS Key Lab Biomed Effects Nanomat & Nanosafety, 11 Beiyitiao, Beijing 100190, Peoples R China; [Luo, Zhen; Duan, Zhongyu] Hebei Univ Technol, Sch Chem Engn & Technol, Tianjin 300130, Peoples R China; [Jiang, Yuxing; Rong, Hongtao] Tianjin Med Univ Gen Hosp, Tianjin 300052, Peoples R China; [Liu, Zimo; Wang, Lei; Yi, Yu; Wang, Hao] Univ Chinese Acad Sci, Beijing 100049, Peoples R China; [Guo, Lamei; Zhang, Li] Tianjin Univ Technol, Sch Environm Sci & Safety Engn, Tianjin 300384, Peoples R China; [Liang, Hongwen] Chongqing Med Univ, Coll Pharm, Chongqing 400016, Peoples R China; [Zhang, Aili] Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai 200240, Peoples R China"

通信作者："Yi, Y; Wang, H (通讯作者)，Natl Ctr Nanosci & Technol NCNST, CAS Ctr Excellence Nanosci, CAS Key Lab Biomed Effects Nanomat & Nanosafety, 11 Beiyitiao, Beijing 100190, Peoples R China.; Yi, Y; Wang, H (通讯作者)，Univ Chinese Acad Sci, Beijing 100049, Peoples R China."

来源：NANO RESEARCH

ESI学科分类：PHYSICS

WOS号：WOS:001184699100004

JCR分区：Q1

影响因子：9.5

年份：2024

卷号：　

期号：　

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文献类型：Article; Early Access

关键词：selenopeptide; self-assembly; atherosclerosis; monocyte adhesion; anti-inflammation

摘要："Atherosclerosis is an inflammatory disease that may cause severe heart disease and stroke. Current pharmacotherapy for atherosclerosis shows limited benefits. In the progression of atherosclerosis, monocyte adhesions and inflammatory macrophages play vital roles. However, precise regulations of inflammatory immune microenvironments in pathological tissues remain challenging. Here, we report an atherosclerotic plaque-targeted selenopeptide nanomedicine for inhibiting atherosclerosis progression by reducing monocyte adhesions and inflammation of macrophages. The targeted nanomedicine has 2.2-fold enhancement in atherosclerotic lesion accumulation. The oxidation-responsibility of selenopeptide enables eliminations of reactive oxygen species and specific release of anti-inflammatory drugs, thereby reducing inflammation responses of macrophages. Notably, we find the oxidative metabolite of selenopeptide, octadecyl selenite, can bind to P-selectin in a high affinity with a dissociation constant of 1.5 mu M. This in situ generated active seleno-species further inhibit monocyte adhesions for anti-inflammation in synergy. With local regulations of monocyte adhesions and inflammations, the selenopeptide nanomedicine achieves 2.6-fold improvement in atherosclerotic plaque inhibition compared with simvastatin in the atherosclerosis mouse model. Meanwhile, the selenopeptide nanomedicine also displays excellent biological safety in both mice and rhesus monkeys. This study provides a safe and effective platform for regulating inflammatory immune microenvironments for inflammatory diseases such as atherosclerosis."

基金机构："National Natural Science Foundation of China [51890892, 22175048, 22007024, 21805058]; National Key R&D Program of China [2018YFE0205400]; Beijing Natural Science Foundation [2232072]"

基金资助正文："This research was financially supported by the National Natural Science Foundation of China (Nos. 51890892, 22175048, 22007024, and 21805058), National Key R&D Program of China (No. 2018YFE0205400), and Beijing Natural Science Foundation (No. 2232072). The authors thank the helpful discussions from Prof. Huaping Xu (from Tsinghua University) and Prof. Ling Zhu (from NCNST)."