Targeted nanoimmunotherapy reduces atherosclerotic plaque burden in mice

This new article publication from Acta Pharmaceutica Sinica B discusses a targeted nanoimmunotherapy designed to restore macrophage clearance of dying cells, promote an anti-inflammatory phenotype, and reduce atherosclerotic plaque burden in mice.

Macrophages are key immune cells in atherosclerotic plaques. In advanced lesions, their ability to remove dying cells, a process known as efferocytosis, becomes impaired, while inflammatory activity contributes to plaque progression and instability. The authors of this article developed a nanotherapeutic platform that combines targeted drug delivery with the immune-modulating activity of phosphorene, a form of black phosphorus. The researchers modified phosphorene nanosheets with the collagen IV-binding peptide KC11 and loaded them with Resolvin D1, a lipid mediator that helps resolve inflammation.

The resulting formulation, PP@KC/RD, accumulated in atherosclerotic plaques and was efficiently taken up by lesional macrophages in mice. Cell experiments showed enhanced efferocytosis and a shift toward an anti-inflammatory M2-like macrophage phenotype. Mechanistic studies linked improved cell clearance to increased expression of the MerTK receptor and reduced CaMKIIγ signaling, while increased PPAR-γ expression supported macrophage reprogramming. In mice with advanced atherosclerosis, intravenous treatment twice weekly for 12 weeks reduced plaque burden more effectively than Resolvin D1 or the targeted carrier alone.

At the study endpoint, plaques covered 9.4% of the total aortic area in the PP@KC/RD group, compared with 32.4% in saline-treated controls. Treated plaques also had smaller necrotic cores and increased collagen cap areas, features consistent with greater plaque stability. Tissue examinations, blood chemistry, and blood cell measurements showed no obvious toxicity under the tested conditions. This research highlights phosphorene's potential to act as both a drug carrier and an immune-modulating component, offering a strategy to address macrophage dysfunction in atherosclerosis. The findings are preclinical, and further research is needed to establish safety and efficacy in people.