Disturbed Flow-Facilitated Margination and Targeting of Nanodisks Protect against Atherosclerosis.
Small
; 19(2): e2204694, 2023 01.
Article
in En
| MEDLINE
| ID: mdl-36403215
ABSTRACT
Disturbed blood flow induces endothelial pro-inflammatory responses that promote atherogenesis. Nanoparticle-based therapeutics aimed at treating endothelial inflammation in vasculature where disturbed flow occurs may provide a promising avenue to prevent atherosclerosis. By using a vertical-step flow apparatus and a microfluidic chip of vascular stenosis, herein, it is found that the disk-shaped versus the spherical nanoparticles exhibit preferential margination (localization and adhesion) to the regions with the pro-atherogenic disturbed flow. By employing a mouse model of carotid partial ligation, superior targeting and higher accumulation of the disk-shaped particles are also demonstrated within disturbed flow areas than that of the spherical particles. In hyperlipidemia mice, administration of disk-shaped particles loaded with hypomethylating agent decitabine (DAC) displays greater anti-inflammatory and anti-atherosclerotic effects compared with that of the spherical counterparts and exhibits reduced toxicity than "naked" DAC. The findings suggest that shaping nanoparticles to disk is an effective strategy for promoting their delivery to atheroprone endothelia.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Atherosclerosis
/
Nanoparticles
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Small
Journal subject:
ENGENHARIA BIOMEDICA
Year:
2023
Document type:
Article
Affiliation country:
China