Remodeling macrophage efferocytosis and phenotype via targeted nanoimmunotherapy for atherosclerosis.
4 affiliations
- 1Department of Critical Care Medicine, Department of Clinical Pharmacy, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Tianfu Jincheng Laboratory, Chengdu 610041, China.
- 2Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA.
- 3Laboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu 610041, China.
- 4Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Abstract
Macrophages within advanced atherosclerotic lesions typically exhibit impaired efferocytosis and tend to adopt a pro-inflammatory M1-like phenotype, leading to the progression of atherosclerosis. Despite this challenge, the development of biocompatible nanotherapeutics capable of effectively remodeling macrophage efferocytosis and phenotype remains elusive. Here, we developed engineered targeted-peptide-modified nanocarriers (PP) and demonstrated their potential to restore macrophage efferocytosis while promoting re-polarization towards an anti-inflammatory M2-like phenotype. Furthermore, PP efficiently facilitated the delivery of an inflammation-resolving-drug to lesional macrophages within advanced atherosclerotic lesions. This combination approach substantially enhanced the anti-atherosclerotic efficacy of PP-based nanomedicine, effectively ameliorating atherosclerosis progression. In advanced plaque-bearing ApoE -/- mice, PP nanomedcine efficiently accumulated in atherosclerotic plaques, notably restoring macrophage efferocytosis, promoting anti-inflammatory M2-like macrophage polarization, and leading to reduced plaque areas and enhanced plaque stability. This study not only underscores the new pleiotropic effects of PP to restore macrophage efferocytosis and modulate macrophage phenotype, but also highlights the promising potential of PP for the treatment of atherosclerosis and diseases associated with macrophage dysfunction.
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BibTeX
@article{he2026remodeling,
title = {{Remodeling macrophage efferocytosis and phenotype via targeted nanoimmunotherapy for atherosclerosis.}},
author = {Zhongshan He and Yaoyao Luo and Yongjiang Li and Shuping Yang and Yingjun Fan and Yi Zhang and Shengbin Liu and Zhuoming Zhou and Chengjian Cao and Haixing Shi and Mengran Guo and Yuting Chen and Yupei Zhang and Duotian Qin and Wei Chen and Xiangrong Song},
journal = {Acta pharmaceutica Sinica. B},
year = {2026},
month = aug,
doi = {10.1016/j.apsb.2026.08.006},
url = {https://europepmc.org/article/MED/42948745},
note = {CC BY},
}
RIS
TY - JOUR
TI - Remodeling macrophage efferocytosis and phenotype via targeted nanoimmunotherapy for atherosclerosis.
AU - Zhongshan He
AU - Yaoyao Luo
AU - Yongjiang Li
AU - Shuping Yang
AU - Yingjun Fan
AU - Yi Zhang
AU - Shengbin Liu
AU - Zhuoming Zhou
AU - Chengjian Cao
AU - Haixing Shi
AU - Mengran Guo
AU - Yuting Chen
AU - Yupei Zhang
AU - Duotian Qin
AU - Wei Chen
AU - Xiangrong Song
PY - 2026
DA - 2026/08/09
JO - Acta pharmaceutica Sinica. B
DO - 10.1016/j.apsb.2026.08.006
UR - https://europepmc.org/article/MED/42948745
AB - Macrophages within advanced atherosclerotic lesions typically exhibit impaired efferocytosis and tend to adopt a pro-inflammatory M1-like phenotype, leading to the progression of atherosclerosis. Despite this challenge, the development of biocompatible nanotherapeutics capable of effectively remodeling macrophage efferocytosis and phenotype remains elusive. Here, we developed engineered targeted-peptide-modified nanocarriers (PP) and demonstrated their potential to restore macrophage efferocytosis while promoting re-polarization towards an anti-inflammatory M2-like phenotype. Furthermore, PP efficiently facilitated the delivery of an inflammation-resolving-drug to lesional macrophages within advanced atherosclerotic lesions. This combination approach substantially enhanced the anti-atherosclerotic efficacy of PP-based nanomedicine, effectively ameliorating atherosclerosis progression. In advanced plaque-bearing ApoE -/- mice, PP nanomedcine efficiently accumulated in atherosclerotic plaques, notably restoring macrophage efferocytosis, promoting anti-inflammatory M2-like macrophage polarization, and leading to reduced plaque areas and enhanced plaque stability. This study not only underscores the new pleiotropic effects of PP to restore macrophage efferocytosis and modulate macrophage phenotype, but also highlights the promising potential of PP for the treatment of atherosclerosis and diseases associated with macrophage dysfunction.
SN - 2211-3835
SN - 2211-3843
ER -