Targeted tilianin lipid nanoparticles for the treatment of atherosclerosis through remodeling lesional macrophage phenotype  

作　　者：Yaoyao Luo Zhongshan He Mengran Guo Xinchun Wang Zhaohui Jin Min Sun Huiling Yang Wanqin Zeng Shengbin Liu Yupei Zhang Guohong Li Xiaoling Yin Shugang Qin Xing Duan Yong'an Hu Xiangrong Song 

机构地区：[1]Department of Critical Care Medicine,Frontiers Science Center for Disease-related Molecular Network,State Key Laboratory of Biotherapy,West China Hospital,Sichuan University,Chengdu 610041,China [2]First Affiliated Hospital of the Medical College,Shihezi University,Shihezi 832008,China [3]College of Medicine,Shihezi University,Shihezi 832002,China

出　　处：《Nano Research》2025年第2期571-585,共15页纳米研究(英文版)

基　　金：This research was supported by the Science and Technology Project of Xinjiang Production and Construction Corps(No.2022AB020);the Youth Fund of National Natural Science Foundation of China(Nos.82104081 and 82400537);the Sichuan Province Science and Technology Support Program(No.2023NSFSC1682,and No.2024NSFSC0714,Zhongshan He);the Postdoctoral Fellowship Program of CPSF under Grant(No.GZC20241133,Zhongshan He);the Sichuan University Postdoctoral Research and Development Fund(No.2024SCU12014);the West China Hospital Postdoctoral Research and Development Fund(No.2024HXBH058);the Sichuan University Postdoctoral Interdisciplinary Innovation Fund(No.JCXK2203).

摘　　要：Remodeling of the lesional macrophages in atherosclerotic plaques from pro-inflammatory M1 to pro-resolving M2 phenotype is emerging as a promising approach to atherosclerosis treatment.Tilianin(Til),as a natural plant-derivedingredient,hasthepotential tosuppress atherosclerosis progression.However,the poorly aqueous solubility and capacity of targeted plaques limit to clinic transformation of Til.Furthermore,whether Til can remodel the lesional macrophage phenotype remains uninvestigated.Herein,we developed a lesional macrophage-targeted Til lipid nanoparticles(FA@Til-LNPs)via folate modification and investigated their therapeutic efficiency and potential mechanisms for atherosclerosis treatment.We observed that the FA@Til-LNPs not only improved solubility and bioavailability,but also actively targeted M1 macrophages in atherosclerotic plaques,and the internalized FA@Til-LNPs could effectively regulate macrophage polarization toward the M2 phenotype.The nanotherapeutics reduced plaque areas and substantially improved plaque stability by effectively reducing necrotic core area and augmenting the collagen cap area in high-fat diet-fed ApoE--mice.Mechanistically,RNA-sequencing analysis revealed that the FA@Til-LNPs inhibited the pro-inflammatory signaling pathway by down-regulating the expression of pro-inflammatory genes associated with cytokine and chemokine pathways in lesional macrophages.This study first developed the innovative targeting nanotherapeutics of Til to regulate macrophage phenotype for atherosclerosis treatment.

关 键 词：ATHEROSCLEROSIS tilianin lipid nanoparticles M1 to M2 remodeling lesional macrophage-targeted 

分 类 号：R73[医药卫生—肿瘤]