Anti-CXCR2 antibody-coated nanoparticles with an erythrocyte-platelet hybrid membrane layer for atherosclerosis therapy

作者全名："Huang, Rongzhong; Zhang, Lujun; Li, Xingsheng; Liu, Fan; Cheng, Xiaoxiao; Ran, Haitao; Wang, Zhigang; Li, Yongyong; Feng, Yuxing; Liang, Liwen; Su, Wenhua; Melgiri, N. D.; Sun, Yang"

作者地址："[Huang, Rongzhong; Li, Xingsheng; Li, Yongyong] Chongqing Med Univ, Affiliated Hosp 2, Precis Med Ctr, Chongqing Municipal Clin Res Ctr Geriatr & Geronto, Chongqing 400010, Peoples R China; [Zhang, Lujun] Second Mil Med Univ, Changhai Hosp, Dept Cardiol, Shanghai, Peoples R China; [Liu, Fan; Cheng, Xiaoxiao; Ran, Haitao; Wang, Zhigang; Sun, Yang] Chongqing Med Univ, Affiliated Hosp 2, Dept Ultrasound, Chongqing Key Lab Ultrasound Mol Imaging, Chongqing 400010, Peoples R China; [Melgiri, N. D.] Impactys Fdn Biomed Res, San Diego, CA USA; [Feng, Yuxing] Ninth Peoples Hosp Chongqing, Dept Rehabil & Pain Med, Chongqing, Peoples R China; [Liang, Liwen; Su, Wenhua] First Peoples Hosp Yunnan Prov, Dept Cardiol, Kunming, Peoples R China"

通信作者："Sun, Y (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Ultrasound, Chongqing Key Lab Ultrasound Mol Imaging, Chongqing 400010, Peoples R China."

来源：JOURNAL OF CONTROLLED RELEASE

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000971363100001

JCR分区：Q1

影响因子：10.5

年份：2023

卷号：356

期号：　

开始页：610

结束页：622

文献类型：Article

关键词：Atherosclerosis; Nanoparticle; CXCR2; CXCL8; IL-8

摘要："Atherosclerosis is the leading cause of mortality globally. RBC-platelet hybrid membrane-coated nanoparticles ([RBC-P]NPs), which biologically mimic platelets in vivo, display evidence of anti-atherosclerotic activity. The efficacy of a targeted RBC-platelet hybrid membrane-coated nanoparticles ([RBC-P]NP)-based approach was investigated as a primary preventive measure against atherosclerosis. A ligand-receptor interactome analysis conducted with circulating platelets and monocytes derived from CAD patients and healthy controls identified CXCL8-CXCR2 as a key platelet ligand-monocyte receptor dyad in CAD patients. Based on this analysis, a novel anti-CXCR2 [RBC-P]NP that specifically binds to CXCR2 and blocks the interaction between CXCL8 and CXCR2 was engineered and characterized. Administering anti-CXCR2 [RBC-P]NPs to Western diet-fed Ldlr(-/-) mice led to diminished plaque size, necrosis, and intraplaque macrophage accumulation relative to control [RBC-P]NPs or vehicle. Importantly, anti-CXCR2 [RBC-P]NPs demonstrated no adverse bleeding/hemorrhagic effects. A series of in vitro experiments was conducted to characterize anti-CXCR2 [RBC-P]NP's mechanism of action in plaque macrophages. Mechanistically, anti-CXCR2 [RBC-P]NPs inhibited p38 alpha (Mapk14)-mediated, pro-inflammatory M1 skewing and corrected efferocytosis in plaque macrophages. This targeted [RBC-P]NP-based approach, in which the cardioprotective effects of anti-CXCR2 [RBC-P]NP therapy overweighs its bleeding/hemorrhagic risks, could potentially be used to proactively manage atherosclerotic progression in at-risk populations."

基金机构："National Natural Science Foundation of China [81960095,81871369]"

基金资助正文："Funding National Natural Science Foundation of China (81960095,81871369) ."