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EXP001885

Paper

Fine Tuning of Core–Shell Structure of Hyaluronic Acid/Cell-Penetrating Peptides/siRNA Nanoparticles for Enhanced Gene Delivery to Macrophages in Antiatherosclerotic Therapy (2018)

Peptide

Penetratin — NPs-2 (HA 200 kDa, low density shell)

Sequence: RQIKIWFQNRRMKWKK

RNA

siRNA

All experiment fields

Experiment Id EXP001885
Paper Fine Tuning of Core–Shell Structure of Hyaluronic Acid/Cell-Penetrating Peptides/siRNA Nanoparticles
Peptide Penetratin — NPs-2 (HA 200 kDa, low density shell)
Delivery Success Class yes
In Vivo Flag yes
Uptake Confirmed yes
Label Confidence high
In Vitro Functional Effect
Endosomal Escape Evidence
Peptide Concentration
Rna Concentration
Mixing Ratio CPP/siRNA N/P = 4:1 (complete complexation); HA coated by adsorption to produce NPs-1/NPs-2/NPs-3.
Formulation Format Core–shell nanoparticle (Penetratin/siRNA core; hyaluronic acid shell for NPs)
Formulation Components Core: penetratin-condensed LOX-1 siRNA (NCs). Shell: HA 200 kDa, low density shell; HAase-responsive de-shielding in plaques/macrophage environment.
Size Nm 141.30
Zeta Mv 22.10
Model Scope in_vivo
Model Type in vivo
Cell Lines Or Primary Cells
Animal Model Male apoE-deficient mice on high-cholesterol diet (16 weeks induction) followed by 12-week treatment.
Administration Route Tail vein (i.v.) injection; 1.5 mg/kg siRNA, twice per week for 12 weeks (pharmacodynamic efficacy).
Output Type In vivo functional delivery: anti-atherosclerotic efficacy (lesion area, lipid, inflammation markers)
Output Value LOX-1 siRNA formulations reduced aortic root lesion area and lipid accumulation; NPs-3 showed the strongest reduction and decreased CD68+ macrophage content and MCP-1 vs controls.
Output Units
Output Notes HA-coated NCs using 200 kDa HA with lower coating density. In vivo ex vivo imaging (Cy5-siRNA 1 mg/kg) showed higher aorta plaque accumulation for HA-coated NPs (highest for NPs-3) vs free siRNA/NCs; therapeutic study shows best efficacy for NPs-3.
Toxicity Notes
Curation Notes