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没食子酸-线粒体靶向序列-HR诱导线粒体靶向的细胞保护作用。

Gallic acid-mitochondria targeting sequence-HR induces mitochondria-targeted cytoprotection.

作者信息

Bae Yoonhee, Kim Goo-Young, Jessa Flores, Ko Kyung Soo, Han Jin

机构信息

Department of Physiology, Cardiovascular and Metabolic Disease Center, Smart Marine Therapeutic Center, Inje University College of Medicine, Busan 47392, Korea.

Division of Applied Medicine, Research Institute for Korea Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea.

出版信息

Korean J Physiol Pharmacol. 2022 Jan 1;26(1):15-24. doi: 10.4196/kjpp.2022.26.1.15.

DOI:10.4196/kjpp.2022.26.1.15
PMID:34965992
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8723982/
Abstract

The development of selective targeting of drug molecules towards the mitochondria is an important issue related to therapy efficacy. In this study, we report that gallic acid (GA)-mitochondria targeting sequence (MTS)-HR exhibits a dual role as a mitochondria-targeting vehicle with antioxidant activity for disease therapy. In viability assays, GA-MTS-HR showed a better rescue action compared to that of MTS-HR. GA-MTS-HR dramatically exhibited cell penetration and intercellular uptake compared to MTS and fit escape from lysosome release to the cytosol. We demonstrated the useful targeting of GA-MTS-HR towards mitochondria in AC16 cells. Also, we observed that the antioxidant properties of mitochondrial-accrued GA-MTSHR alleviated cell damage by reactive oxygen species production and disrupted mitochondrial membrane potential. GA-MTS-HR showed a very increased cytoprotective effect against anticancer activity compared to that of MTS-HR. We showed that GA-MTS-HR can act as a vehicle for mitochondria-targeting and as a reagent for therapeutic applications intended for cardiovascular disease treatment.

摘要

药物分子对线粒体的选择性靶向开发是一个与治疗效果相关的重要问题。在本研究中，我们报告了没食子酸（GA）-线粒体靶向序列（MTS）-HR作为一种具有抗氧化活性的线粒体靶向载体，在疾病治疗中发挥双重作用。在活力测定中，GA-MTS-HR比MTS-HR表现出更好的挽救作用。与MTS相比，GA-MTS-HR显著表现出细胞穿透和细胞间摄取，并能从溶酶体释放到细胞质中逃逸。我们证明了GA-MTS-HR在AC16细胞中对线粒体的有效靶向。此外，我们观察到线粒体积累的GA-MTSHR的抗氧化特性减轻了活性氧产生引起的细胞损伤，并破坏了线粒体膜电位。与MTS-HR相比，GA-MTS-HR对抗癌活性表现出非常增强的细胞保护作用。我们表明，GA-MTS-HR可以作为线粒体靶向的载体，也可以作为用于心血管疾病治疗的治疗应用试剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae74/8723982/7d6d06bf2b0d/kjpp-26-1-15-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae74/8723982/84cdc9bb8de8/kjpp-26-1-15-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae74/8723982/475375880f40/kjpp-26-1-15-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae74/8723982/4a90079423f4/kjpp-26-1-15-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae74/8723982/18ca5fab0a71/kjpp-26-1-15-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae74/8723982/a5597523bf7e/kjpp-26-1-15-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae74/8723982/7d6d06bf2b0d/kjpp-26-1-15-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae74/8723982/84cdc9bb8de8/kjpp-26-1-15-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae74/8723982/7d064c619d50/kjpp-26-1-15-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae74/8723982/dd60ae4e22da/kjpp-26-1-15-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae74/8723982/475375880f40/kjpp-26-1-15-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae74/8723982/4a90079423f4/kjpp-26-1-15-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae74/8723982/18ca5fab0a71/kjpp-26-1-15-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae74/8723982/a5597523bf7e/kjpp-26-1-15-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae74/8723982/7d6d06bf2b0d/kjpp-26-1-15-f8.jpg

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Biocompatible Polymer Nanoparticles for Drug Delivery Applications in Cancer and Neurodegenerative Disorder Therapies.用于癌症和神经退行性疾病治疗中药物递送应用的生物相容性聚合物纳米颗粒
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