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ACS Applied Materials & Interfaces

ACS Applied Materials & Interfaces

IF: 8.3
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CpG-Conjugated Silver Nanoparticles as a Multifunctional Nanomedicine to Promote Macrophage Efferocytosis and Repolarization for Atherosclerosis Therapy

Published:1 November 2023 DOI: 10.1021/acsami.3c11227 PMID: 37910772
Cui Tang, Hui Wang, Lina Guo, Chan Zou, Jianming Hu, Hanyong Zhang, Wenhu Zhou* and Guoping Yang*, 

Abstract

Atherosclerosis (AS) is a major contributor to cardiovascular diseases, necessitating the development of novel therapeutic strategies to alleviate plaque burden. Macrophage efferocytosis, the process by which macrophages clear apoptotic and foam cells, plays a crucial role in plaque regression. However, this process is impaired in AS lesions due to the overexpression of CD47, which produces a “do not eat me” signal. In this study, we investigated the potential of CpG, a toll-like receptor 9 agonist, to enhance macrophage efferocytosis for AS therapy. We demonstrated that CpG treatment promoted the engulfment of CD47-positive apoptotic cells and foam cells by macrophages. Mechanistically, CpG induced a metabolic shift in macrophages characterized by enhanced fatty acid oxidation and de novo lipid biosynthesis, contributing to its pro-efferocytic effect. To enable in vivo application, we conjugated CpG on silver nanoparticles (AgNPs) to form CpG-AgNPs, which could protect CpG from biological degradation, promote its cellular uptake, and release CpG in response to intracellular glutathione. Combining the intrinsic antioxidative and anti-inflammatory abilities of AgNPs, such nanomedicine displayed multifunctionalities to simultaneously promote macrophage efferocytosis and repolarization. In an ApoE–/– mouse model, intravenous administration of CpG-AgNPs effectively targeted atherosclerotic plaques and exhibited potent therapeutic efficacy with excellent biocompatibility. Our study provides valuable insights into CpG-induced macrophage efferocytosis and highlights the potential of CpG-AgNPs as a promising therapeutic strategy for AS.

Substances (2)

Materials
Procduct Name CAS Molecular Formula Supplier Price
BMS 303141 943962-47-8 C19H15Cl2NO4S 146 suppliers $15.00-$2691.10
BMS 303141 943962-47-8 C19H15Cl2NO4S 146 suppliers $15.00-$2691.10

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