TiO2-纳米粒子增强声动力疗法用于预防后囊翳和铁沉着症的机制探索

IF 5 2区 医学 Q1 OPHTHALMOLOGY Investigative ophthalmology & visual science Pub Date : 2024-10-01 DOI:10.1167/iovs.65.12.24
Yuanyuan Li, Pingjun Chang, Liming Xu, Zehui Zhu, Man Hu, Jiaying Cen, Siyan Li, Yun-E Zhao
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引用次数: 0

摘要

目的:探讨以二氧化钛纳米颗粒(TiO2-NPs)为声敏化剂的声动力疗法(SDT)在预防后囊混浊(PCO)方面的应用和潜在的铁蛋白沉积机制:方法:我们采用旋涂法制作了TiO2-NP涂层眼内透镜(TiO2-IOLs),然后用超声波激活光敏剂TiO2。用人晶状体上皮细胞(HLECs)进行了体外实验,以探索合适的 TiO2 浓度和超声参数。研究内容包括活性氧(ROS)生成、谷胱甘肽(GSH)消耗、谷胱甘肽过氧化物酶4(GPX4)Western印迹分析、脂质过氧化测定和转录组学分析。最后,将二氧化钛人工晶体植入兔眼,以探索 SDT 的体内性能:通过体外和体内实验,该研究确定了持续时间为 5 分钟、频率为 1 兆赫、占空比为 50%、强度为 1.2 瓦/平方厘米的超声参数对于杀死 HLECs 而不损伤其他眼部结构是可靠有效的。体外实验表明,SDT 会产生过量的 ROS,从而破坏线粒体膜电位并显著降低 GSH 含量。此外,还观察到 GPX4 的下调、脂质过氧化物的积累和线粒体形态的改变,这表明铁变态反应可能是其基本机制。RNA 序列分析结果还显示,多个促铁蛋白沉积基因和铁蛋白沉积标记基因 PTGS2 的表达增加。动物实验初步证明了 SDT 在体内治疗 PCO 的安全性和有效性:结论:TiO2-IOLs 与 SDT 结合使用,可通过产生 ROS 和细胞内铁变态反应有效预防 PCO。
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TiO2-Nanoparticle-Enhanced Sonodynamic Therapy for Prevention of Posterior Capsular Opacification and Ferroptosis Exploration of Its Mechanism.

Purpose: To explore the application and potential ferroptosis mechanisms of sonodynamic therapy (SDT) using titanium dioxide nanoparticles (TiO2-NPs) as sonosensitizers for the prevention of posterior capsule opacification (PCO).

Methods: We fabricated TiO2-NP-coated intraocular lenses (TiO2-IOLs) using the spin-coating method, followed by ultrasound activation of the photosensitizer TiO2. In vitro experiments were performed with human lens epithelial cells (HLECs) to explore the appropriate concentration of TiO2 and ultrasonic parameters. Investigations included reactive oxygen species (ROS) generation, glutathione (GSH) depletion, glutathione peroxidase 4 (GPX4) western blot analysis, lipid peroxidation assays, and transcriptomics analysis. Finally, TiO2-IOLs were implanted in rabbit eyes to explore the in vivo performance of SDT.

Results: Through both in vitro and in vivo experiments, the study determined that the ultrasound parameters of 5-minute duration, 1-MHz frequency, 50% duty cycle, and 1.2-W/cm2 intensity were reliable and valid for killing HLECs without damaging other ocular structures. In vitro experiments demonstrated that SDT generated excess ROS, which disrupted the mitochondrial membrane potential and significantly reduced the GSH content. Additionally, the downregulation of GPX4, accumulation of lipid peroxides, and alteration of mitochondrial morphology were observed, suggesting that ferroptosis may be the underlying mechanism. The RNA-sequencing analysis results also showed an increase in the expression of multiple pro-ferroptosis genes and the ferroptosis marker gene PTGS2. Animal experiments preliminarily demonstrated the safety and effectiveness of SDT in treating PCO in vivo.

Conclusions: TiO2-IOLs combined with SDT effectively prevented PCO by generating ROS and intracellular ferroptosis.

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来源期刊
CiteScore
6.90
自引率
4.50%
发文量
339
审稿时长
1 months
期刊介绍: Investigative Ophthalmology & Visual Science (IOVS), published as ready online, is a peer-reviewed academic journal of the Association for Research in Vision and Ophthalmology (ARVO). IOVS features original research, mostly pertaining to clinical and laboratory ophthalmology and vision research in general.
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