A pioneering study led by researchers from Tongji University School of Medicine, Shanghai Jiao Tong University School of Medicine and Naval Medical University has unveiled a novel nanomedicine, mPEG@ELA-11, which demonstrates significant potential in treating atherosclerosis (AS), a leading cause of cardiovascular diseases globally. The research, published in BME Frontiers, introduces a pH-responsive nanocarrier designed to enhance the therapeutic efficacy of the peptide ELA-11.
Atherosclerosis is characterized by lipid accumulation and inflammation in arterial walls. The study found that the APELA gene, encoding ELA-11, is significantly downregulated in human carotid atherosclerotic plaques, particularly in unstable lesions. ELA-11 was shown to suppress macrophage foam cell formation, M1 polarization, and apoptosis by inhibiting the AKT-mediated endoplasmic reticulum (ER) stress pathway, as confirmed through in vitro experiments.
To address limitations of ELA-11, such as short half-life and poor bioavailability, researchers developed mPEG@ELA-11, a nanocarrier with optimal size (~35 nm) and pH-dependent release properties. In vivo experiments using ApoE -/- mice revealed that mPEG@ELA-11 significantly reduced atherosclerotic plaque area and necrotic core size compared to free ELA-11, attributed to its targeted release mechanism. Ex vivo fluorescence imaging showed preferential accumulation in the liver and aorta, with minimal uptake in other organs.
The study highlights the therapeutic potential of mPEG@ELA-11, offering a promising strategy for managing atherosclerosis. Future research will focus on long-term safety, immunogenicity, and regulatory compliance to advance clinical translation.
BME Frontiers
Experimental study
Not applicable
mPEG@ELA-11 Alleviates Atherosclerosis via AKT-ER Stress-Mediated Macrophage Modulation
25-Nov-2025