Journal: Bioactive Materials

Article Title: A foam cell-targeted lipophagy restoration strategy stabilizes vulnerable atherosclerotic plaques

doi: 10.1016/j.bioactmat.2026.02.041

Figure Lengend Snippet: Schematic of the anti-atherosclerotic mechanism of OPN-HMCN@MLT. ( A ) The study commenced with the synthesis of mesoporous carbon nanospheres (MCN) functionalized with an OPN-binding peptide and hyaluronic acid to construct the OPN-HMCN nanoplatform. The OPN-binding peptide was designed to recognize OPN enriched in the extracellular matrix and on the surface of foam cells, thereby enabling selective accumulation in OPN-rich pathological regions. Following OPN recognition, OPN-HMCN@MLT undergoes CD44-dependent endocytosis. Melatonin (MLT), a lipid autophagy–promoting agent, was subsequently encapsulated within the nanocarrier to form OPN-HMCN@MLT. Firstly, the released MLT can bind to and upregulate the expression of PPARα and PPARγ, which then promote the expression of downstream genes (ABCA1, ABCG1, ACOX-1, and CTP1A) and trigger the lipophagy. ( B ) Subsequently, its lipophagy-enhancing effects, including ABCA1/G1-mediated cholesterol efflux and CTP1A/ACOX-1-mediated mitochondrial fatty acid oxidation, were studied to confirm the reversal of foam cell formation. ( C ) These effects eventually promote foam cells to reverse into macrophages. Abbreviations: MCN, mesoporous carbon nanoparticle; OPN, osteopontin; MLT, melatonin; LDL, low-density lipoprotein; ox-LDL, oxidized low-density lipoprotein; PA, Photoacoustic.

Article Snippet: To block nonspecific binding, membranes were incubated with 5% skim milk for 1 h. Thereafter, membranes were incubated overnight at 4 °C with primary antibodies against ABCA1, ABCG1, ACOX1, CPT1A, LC3 (ab192890, 1:2000, abcam), LAMP1 (84658-5-RR, 1:8000, Proteintech), PPARα (66826-1-Ig, 1:3000, Proteintech), PPARγ (66936-1-Ig, 1:10000, Proteintech), P62 (18420-1-AP, 1:10000, Proteintech), MCAD (55210-1-AP, 1:3000, Proteintech), LCAD (17526-1-AP, 1:10000, Proteintech), tubulin (80762-1-RR, 1:10000, Proteintech), GAPDH (60004-1-Ig, 1:50000, Proteintech), and β-actin (66009-1-Ig, 1:20000, Proteintech).

Techniques: Binding Assay, Construct, Expressing

Journal: Bioactive Materials

Article Title: A foam cell-targeted lipophagy restoration strategy stabilizes vulnerable atherosclerotic plaques

doi: 10.1016/j.bioactmat.2026.02.041

Figure Lengend Snippet: In vitro evaluation of foam cell lipid accumulation and lipophagy activation following OPN-HMCN@MLT treatment. ( A - C ) ORO and BODIPY staining images and corresponding quantification of ORO and BODIPY positive areas of RAW264.7 cells under different stimulations (n = 5, scale bar for ORO: 100 μm, scale bar for BODIPY: 20 μm). ( D ) Bio-TEM images of RAW264.7 cells post various treatments (n = 5, scale bars 1.0 μm). Green arrows indicate nanoparticles. ( E , F ) Morphometric analysis determined the mean number and area (μm 2 ) of LDs per cell section. ( G ) Confocal images depicting lipophagy flux in foam cells following different treatments (n = 5 biological replicates, scale bars: 10 μm). ( H - J ) The quantities of acidified autophagosomes (GFP-RFP+), neutral autophagosomes (GFP + RFP+), and LDs labeled with BODIPY were measured per cell for each condition. (K to N) Representative Western blot images and quantitative analysis of LC3, LAMP1, and P62 expression in foam cells. ∗ P < 0.05, ∗∗ P < 0.01, ∗∗∗ P < 0.001, and ∗∗∗∗ P < 0.0001.

Article Snippet: To block nonspecific binding, membranes were incubated with 5% skim milk for 1 h. Thereafter, membranes were incubated overnight at 4 °C with primary antibodies against ABCA1, ABCG1, ACOX1, CPT1A, LC3 (ab192890, 1:2000, abcam), LAMP1 (84658-5-RR, 1:8000, Proteintech), PPARα (66826-1-Ig, 1:3000, Proteintech), PPARγ (66936-1-Ig, 1:10000, Proteintech), P62 (18420-1-AP, 1:10000, Proteintech), MCAD (55210-1-AP, 1:3000, Proteintech), LCAD (17526-1-AP, 1:10000, Proteintech), tubulin (80762-1-RR, 1:10000, Proteintech), GAPDH (60004-1-Ig, 1:50000, Proteintech), and β-actin (66009-1-Ig, 1:20000, Proteintech).

Techniques: In Vitro, Activation Assay, Staining, Labeling, Western Blot, Expressing