期刊
PHARMACEUTICS
卷 13, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/pharmaceutics13091414
关键词
magnetic nanoparticles; dextran; protocatechuic acid; anti-inflammatory activity; endothelial cells; macrophages
资金
- Romanian Ministry of Research, Innovation, and Digitization, CNCS/CCCDI-UEFISCDI, within PNCDI III [PN-III-P1-1.2-PCCDI-2017-0697, 13PCCDI/2018]
- Romanian Academy
This study developed dextran shell-iron oxide core nanoparticles loaded with protocatechuic acid (PCA) and evaluated their anti-inflammatory potential at non-cytotoxic and therapeutically relevant concentrations. The results showed that MNP-Dex/PCA reduced inflammatory molecules levels in activated endothelial cells and M1-type macrophages, along with decreased monocyte adhesion, through the modulation of ERK1/2, p38-alpha MAPKs, and NF-kB signaling pathways. These findings support the future development of dextran shell-magnetic core nanoparticles as theranostic tools for vascular inflammation therapy.
Vascular inflammation plays a crucial role in the progression of various pathologies, including atherosclerosis (AS), and thus it has become an attractive therapeutic target. The protocatechuic acid (PCA), one of the main metabolites of complex polyphenols, is endowed with anti-inflammatory activity, but its formulation into nanocarriers may increase its bioavailability. In this study, we developed and characterized dextran shell-iron oxide core nanoparticles loaded with PCA (MNP-Dex/PCA) and assessed their cytotoxicity and anti-inflammatory potential on cells acting as key players in the onset and progression of AS, namely, endothelial cells (EC) and monocytes/macrophages. The results showed that MNP-Dex/PCA exert an anti-inflammatory activity at non-cytotoxic and therapeutically relevant concentrations of PCA (350 mu M) as supported by the reduced levels of inflammatory molecules such as MCP-1, IL-1 beta, TNF-alpha, IL-6, and CCR2 in activated EC and M1-type macrophages and functional monocyte adhesion assay. The anti-inflammatory effect of MNP-Dex/PCA was associated with the reduction in the levels of ERK1/2 and p38-alpha mitogen-activated protein kinases (MAPKs) and NF-kB transcription factor. Our data support the further development of dextran shell-magnetic core nanoparticles as theranostic nanoparticles for guidance, imaging, and therapy of vascular inflammation using PCA or other anti-inflammatory compounds.
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