Related Experiment Video
Updated: May 21, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
ROS-responsive nanoparticles with selenomethionine for ferroptosis modulation in abdominal aortic aneurysm
Haipeng He1, Lei Chen2, Jiaxin Peng1
1Department of Vascular Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Abstract:
Oxidative stress, particularly ROS accumulation, plays a key role in the development of abdominal aortic aneurysm (AAA). Surgical treatments and current drugs for AAA have limitations, including lack of specificity and significant side effects. This study constructed ROS-responsive nanoparticles using phenylthio-modified dendritic polylysine (PDP) loaded with selenomethionine (PDPs-Se) for AAA treatment, and elucidated its mechanism of action. In-vitro studies revealed that PDPs-Se enhanced the clearance of ROS by increasing the levels of superoxide dismutase (SOD) and glutathione (GSH) while reducing malondialdehyde (MDA) levels. Furthermore, PDPs-Se upregulated the expression levels of GPX4, SLC7A11, and FTH1 to suppress ferroptosis and modulate the differentiation of vascular smooth muscle cells (VSMCs) from a synthetic to a contractile phenotype. In-vivo experiments revealed that PDPs-Se attenuated the progression of AAA by inhibiting oxidative stress responses and improving the aortic wall thickness, indicating its potential as an approach for AAA therapy.
Insights
This study developed novel ROS-responsive nanoparticles (PDPs-Se) to treat abdominal aortic aneurysm (AAA). The nanoparticles effectively reduced oxidative stress and ferroptosis, showing promise for AAA therapy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cardiovascular Research
Background:
- Oxidative stress, specifically reactive oxygen species (ROS) accumulation, is a critical factor in abdominal aortic aneurysm (AAA) development.
- Current AAA treatments have limitations, including poor specificity and adverse side effects.
Purpose of the Study:
- To develop and characterize ROS-responsive nanoparticles (PDPs-Se) for targeted AAA treatment.
- To elucidate the mechanism of action of PDPs-Se in mitigating AAA progression.
Main Methods:
- Construction of phenylthio-modified dendritic polylysine (PDP) nanoparticles loaded with selenomethionine (PDPs-Se).
- In vitro assessment of ROS scavenging, antioxidant enzyme levels (SOD, GSH), lipid peroxidation (MDA), ferroptosis markers (GPX4, SLC7A11, FTH1), and vascular smooth muscle cell (VSMC) phenotype modulation.
- In vivo evaluation of PDPs-Se efficacy in an AAA animal model, assessing oxidative stress and aortic wall integrity.
Main Results:
- In vitro studies demonstrated that PDPs-Se effectively scavenged ROS, increased SOD and GSH levels, and reduced MDA.
- PDPs-Se upregulated GPX4, SLC7A11, and FTH1, suppressing ferroptosis and promoting VSMC contractile phenotype.
- In vivo experiments showed that PDPs-Se attenuated AAA progression by inhibiting oxidative stress and improving aortic wall thickness.
Conclusions:
- PDPs-Se nanoparticles represent a promising therapeutic strategy for AAA by targeting oxidative stress and ferroptosis.
- The developed nanoparticles offer a potential alternative to current AAA treatments with improved specificity and reduced side effects.
