Mitochondria-Targeted SS-31 Conjugated Liposome Attenuate Oxidative Stress in Endothelial and Skeletal Muscle Cells.

IF 1.8 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE
Eun-Mi Kim, Yeon-Hee Han, Phil-Sun Oh, Wang Qi, Seok-Tae Lim, Hwan-Jeong Jeong
{"title":"Mitochondria-Targeted SS-31 Conjugated Liposome Attenuate Oxidative Stress in Endothelial and Skeletal Muscle Cells.","authors":"Eun-Mi Kim, Yeon-Hee Han, Phil-Sun Oh, Wang Qi, Seok-Tae Lim, Hwan-Jeong Jeong","doi":"10.1159/000547281","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Mitochondria play a pivotal role as therapeutic targets in a range of disorders, including metabolic and neurodegenerative diseases. SS31, a peptide engineered to target mitochondria, offers potent antioxidant activity, positioning it as a promising therapeutic option. Nevertheless, the hydrophilic profile of SS31 poses challenges such as reduced stability, suboptimal delivery, and poor mitochondrial localization in clinical applications.</p><p><strong>Aim: </strong>This study was designed to develop a mitochondria-targeted liposomal carrier by conjugating SS31KRKC to the liposome surface (SS31-LP) and to investigate its biological effects in vitro.</p><p><strong>Methods: </strong>A lysine-arginine-lysine-cysteine (KRKC) linker was incorporated with SS31 to facilitate surface conjugation to liposomes via thiol-based coupling. The hydrodynamic diameter and zeta potential of the resulting formulations were quantified to determine the optimal lipid-to-peptide ratio for mitochondrial targeting. The in vitro mitochondrial localization, cytotoxicity, antioxidant potential, and anti-apoptotic efficacy of SS31-LP were evaluated in HUVEC and C2C12 cells.</p><p><strong>Results: </strong>SS31-LP demonstrated pronounced mitochondrial localization and showed variable cellular internalization based on zeta potential. Pretreatment with SS31-LP enhanced cellular viability, mitigated oxidative damage, and reduced apoptosis in response to oxidative stress caused by H₂O₂ or blue LEDs.</p><p><strong>Conclusion: </strong>Overall, SS31-LP presents as a valuable therapeutic strategy for cellular protection against oxidative injury and may be an advantageous platform for targeted drug delivery applications.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"1-30"},"PeriodicalIF":1.8000,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Vascular Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000547281","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Mitochondria play a pivotal role as therapeutic targets in a range of disorders, including metabolic and neurodegenerative diseases. SS31, a peptide engineered to target mitochondria, offers potent antioxidant activity, positioning it as a promising therapeutic option. Nevertheless, the hydrophilic profile of SS31 poses challenges such as reduced stability, suboptimal delivery, and poor mitochondrial localization in clinical applications.

Aim: This study was designed to develop a mitochondria-targeted liposomal carrier by conjugating SS31KRKC to the liposome surface (SS31-LP) and to investigate its biological effects in vitro.

Methods: A lysine-arginine-lysine-cysteine (KRKC) linker was incorporated with SS31 to facilitate surface conjugation to liposomes via thiol-based coupling. The hydrodynamic diameter and zeta potential of the resulting formulations were quantified to determine the optimal lipid-to-peptide ratio for mitochondrial targeting. The in vitro mitochondrial localization, cytotoxicity, antioxidant potential, and anti-apoptotic efficacy of SS31-LP were evaluated in HUVEC and C2C12 cells.

Results: SS31-LP demonstrated pronounced mitochondrial localization and showed variable cellular internalization based on zeta potential. Pretreatment with SS31-LP enhanced cellular viability, mitigated oxidative damage, and reduced apoptosis in response to oxidative stress caused by H₂O₂ or blue LEDs.

Conclusion: Overall, SS31-LP presents as a valuable therapeutic strategy for cellular protection against oxidative injury and may be an advantageous platform for targeted drug delivery applications.

线粒体靶向SS-31偶联脂质体减轻内皮细胞和骨骼肌细胞的氧化应激。
背景:线粒体在包括代谢性和神经退行性疾病在内的一系列疾病中作为治疗靶点发挥着关键作用。SS31是一种针对线粒体的肽,具有强大的抗氧化活性,使其成为一种有前景的治疗选择。然而,在临床应用中,SS31的亲水特性带来了一些挑战,如稳定性降低、递送不理想和线粒体定位不良。目的:将SS31KRKC偶联至脂质体表面,制备线粒体靶向脂质体载体(SS31-LP),并研究其体外生物学效应。方法:将赖氨酸-精氨酸-赖氨酸-半胱氨酸(KRKC)连接体与SS31结合,通过巯基偶联促进与脂质体的表面偶联。对所得配方的流体动力学直径和zeta电位进行量化,以确定线粒体靶向的最佳脂质与肽比。在HUVEC和C2C12细胞中评价SS31-LP的体外线粒体定位、细胞毒性、抗氧化潜能和抗凋亡作用。结果:SS31-LP显示出明显的线粒体定位,并显示出基于zeta电位的可变细胞内化。SS31-LP预处理可提高细胞活力,减轻氧化损伤,减少h2o2或蓝色led引起的氧化应激引起的细胞凋亡。结论:总的来说,SS31-LP是一种有价值的细胞氧化损伤治疗策略,可能是靶向给药应用的有利平台。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Journal of Vascular Research
Journal of Vascular Research 医学-生理学
CiteScore
3.40
自引率
0.00%
发文量
25
审稿时长
>12 weeks
期刊介绍: The ''Journal of Vascular Research'' publishes original articles and reviews of scientific excellence in vascular and microvascular biology, physiology and pathophysiology. The scope of the journal covers a broad spectrum of vascular and lymphatic research, including vascular structure, vascular function, haemodynamics, mechanics, cell signalling, intercellular communication, growth and differentiation. JVR''s ''Vascular Update'' series regularly presents state-of-the-art reviews on hot topics in vascular biology. Manuscript processing times are, consistent with stringent review, kept as short as possible due to electronic submission. All articles are published online first, ensuring rapid publication. The ''Journal of Vascular Research'' is the official journal of the European Society for Microcirculation. A biennial prize is awarded to the authors of the best paper published in the journal over the previous two years, thus encouraging young scientists working in the exciting field of vascular biology to publish their findings.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信