Curcumin-Loaded Biohybrid Nanoparticles Modulating Inflammation and Reducing Lipid Accumulation in Atherosclerotic Plaques for Atherosclerosis Treatment

Atherosclerosis is critically driven by inflammation, inadequately addressed by current lipid-lowering therapies. Curcumin has anti-inflammatory and antioxidant properties but poor bioavailability. We develop a biohybrid nanoparticle, termed CP@Leuko, featuring a curcumin-loaded poly(lactic- co -glycolic) acid core within a leukocyte membrane protein-modified zwitterionic lipid shell. The coating enables active targeting of inflamed plaques, resulting in approximately 3-fold greater accumulation in the aortas of ApoE–/– mice versus controls. CP@Leuko modulates inflammation by reducing TNF-α and elevating IL-10 levels in serum and aortic tissues. The treatment attenuates plaque progression, reducing en face aortic plaque area from 25.15% to 11.76% and the aortic root lesion area from 36.69% to 17.10%. It decreases the necrotic core size by about 16.24% while increasing collagen content approximately 1.8-fold, thereby enhancing plaque stability. The formulation significantly improves serum lipid profiles and demonstrates excellent biocompatibility. In summary, CP@Leuko represents a targeted nanotherapeutic strategy leveraging anti-inflammatory efficacy for atherosclerosis treatment.