Phosphorene nanosheets with Resolvin D1 reduce plaques in mice

Researchers have described a targeted nanoplatform based on phosphorene, a form of black phosphorus, that restored the clearance of dying cells by macrophages and reduced atherosclerotic plaque area in mice, according to a paper in Acta Pharmaceutica Sinica B. doi.org In ApoE−/− mice with advanced atherosclerosis, plaques covered 9.4% of the total aortic area in the group given the full formulation, compared with 32.4% in saline-treated controls. doi.org

In advanced lesions, macrophages lose the ability to remove dying cells, a process called efferocytosis, and tend to adopt a pro-inflammatory M1-like phenotype. Both changes contribute to plaque progression and instability. doi.org

Design of the nanoplatform

The authors modified phosphorene nanosheets with KC11, a peptide that binds collagen IV, and loaded them with Resolvin D1, a lipid mediator that helps resolve inflammation. The resulting formulation is called PP@KC/RD. In mice, it accumulated in atherosclerotic plaques and was efficiently taken up by macrophages in the lesions. doi.org

In cell experiments, the formulation enhanced efferocytosis and shifted macrophages toward an anti-inflammatory M2-like phenotype. Mechanistic studies linked the improved clearance to higher expression of the MerTK receptor and reduced CaMKIIγ signaling. Increased PPAR-γ expression supported the reprogramming of the macrophages. doi.org

Results in mice

The mice received intravenous treatment twice a week for 12 weeks. The full formulation reduced plaque burden more effectively than Resolvin D1 alone or the targeted carrier alone. doi.org

Plaques in the treated animals also had smaller necrotic cores and larger collagen cap areas. The authors describe these features as consistent with greater plaque stability. doi.org

Tissue examinations, blood chemistry and blood cell measurements showed no obvious toxicity under the tested conditions. doi.org

The authors suggest that phosphorene can serve both as a drug carrier and as an immune-modulating component. The findings are preclinical, and further research is needed to establish safety and efficacy in people. doi.org

Phosphorene nanosheets with Resolvin D1 cut plaque area to 9.4% in mice with atherosclerosis

Design of the nanoplatform

Results in mice

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