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Macrophage Membrane-Encapsulated Dopamine-Modified Poly Cyclodextrin Multifunctional Biomimetic Nanoparticles for Atherosclerosis Therapy.

Authors :
Zhu L
Zhong Y
Yan M
Ni S
Zhao X
Wu S
Wang G
Zhang K
Chi Q
Qin X
Li C
Huang X
Wu W
Source :
ACS applied materials & interfaces [ACS Appl Mater Interfaces] 2024 Jun 26; Vol. 16 (25), pp. 32027-32044. Date of Electronic Publication: 2024 Jun 12.
Publication Year :
2024

Abstract

Atherosclerotic plaques exhibit high cholesterol deposition and oxidative stress resulting from high reactive oxygen species (ROS). These are the major components in plaques and the main pro-inflammatory factor. Therefore, it is crucial to develop an effective therapeutic strategy that can simultaneously address the multiple pro-inflammatory factors via removing cholesterol and inhibiting the overaccumulated ROS. In this study, we constructed macrophage membrane-encapsulated biomimetic nanoparticles (MM@DA-pCD@MTX), which not only alleviate cholesterol deposition at the plaque lesion via reverse cholesterol transport but also scavenge the overaccumulated ROS. β-Cyclodextrin (β-CD) and the loaded methotrexate (MTX) act synergistically to induce cholesterol efflux for inhibiting the formation of foam cells. Among them, MTX up-regulated the expression of ABCA1, CYP27A1, and SR-B1. β-CD increased the solubility of cholesterol crystals. In addition, the ROS scavenging property of dopamine (DA) was perfectly preserved in MM@DA-pCD@MTX, which could scavenge the overaccumulated ROS to alleviate the oxidative stress at the plaque lesion. Last but not least, MM-functionalized "homing" targeting of atherosclerotic plaques not only enables the targeted drug delivery but also prolongs in vivo circulation time and drug half-life. In summary, MM@DA-pCD@MTX emerges as a potent, multifunctional therapeutic platform for AS treatment, offering a high degree of biosafety and efficacy in addressing the complex pathophysiology of atherosclerosis.

Details

Language :
English
ISSN :
1944-8252
Volume :
16
Issue :
25
Database :
MEDLINE
Journal :
ACS applied materials & interfaces
Publication Type :
Academic Journal
Accession number :
38867426
Full Text :
https://doi.org/10.1021/acsami.4c04431