CpG-Conjugated Silver
Nanoparticles as a Multifunctional
Nanomedicine to Promote Macrophage Efferocytosis and Repolarization
for Atherosclerosis Therapy
posted on 2023-11-01, 19:20authored byCui Tang, Hui Wang, Lina Guo, Chan Zou, Jianming Hu, Hanyong Zhang, Wenhu Zhou, Guoping Yang
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.