Suppr超能文献

超声靶向阳离子微泡介导的基因转染及对视网膜新生血管形成的抑制作用

Ultrasound-targeted cationic microbubble-mediated gene transfection and inhibition of retinal neovascularization.

作者信息

Wu Ming-Xing, Zhou Yu, Zhou Xi-Yuan, Xu Yan

机构信息

Department of Ophthalmology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.

出版信息

Int J Ophthalmol. 2022 Jun 18;15(6):876-885. doi: 10.18240/ijo.2022.06.04. eCollection 2022.

Abstract

AIM

To investigate whether ultrasound-targeted cationic microbubbles (CMBs) destruction could deliver endostatin-green fluorescent protein (GFP) plasmids efficiently to the human retinal endothelial cells (HRECs) and inhibit retinal neovascularization in mice.

METHODS

CMBs were prepared and the presentation of GFP reporter was confirmed by flow cytometry and laser confocal microscopy. Experiments assessing HRECs migration and vascular formation were performed to evaluate gene therapy's efficiency A mouse model of oxygen-induced retinopathy was employed and the expression of Bcl-xl, Bcl-2, vascular endothelial growth factor (VEGF) and endostatin in the retina of mice were determined by Western blotting and quantitative polymerase chain reaction (qPCR). The expression of endostatin-GFP in the retina was examined by laser confocal microscopy at 5, 14, and 28d after treatment.

RESULTS

The gene expression of endostatin was the highest in the group of the CMBs. Besides, the inhibition and antiangiogenesis effect of the migration and development of HRECs were improved following treatment with CMBs compared with the other groups . , retinal neovascularization was significantly inhibited and the fluorescence intensity of endostatin-GFP in the mouse retina was importantly higher in the group of CMBs than that in other groups.

CONCLUSION

The research illustrates ultrasound-targeted CMBs destruction possessed distinct effect on the inhibition of the vascular formation and the development of retinal neovascularization both and .

摘要

目的

研究超声靶向破坏阳离子微泡(CMBs)能否将内皮抑素-绿色荧光蛋白(GFP)质粒有效递送至人视网膜内皮细胞(HRECs),并抑制小鼠视网膜新生血管形成。

方法

制备CMBs,通过流式细胞术和激光共聚焦显微镜确认GFP报告基因的表达。进行评估HRECs迁移和血管形成的实验以评价基因治疗的效果。采用氧诱导视网膜病变小鼠模型,通过蛋白质免疫印迹法和定量聚合酶链反应(qPCR)检测小鼠视网膜中Bcl-xl、Bcl-2、血管内皮生长因子(VEGF)和内皮抑素的表达。在治疗后第5、14和28天,通过激光共聚焦显微镜检查视网膜中内皮抑素-GFP的表达。

结果

内皮抑素基因表达在CMBs组中最高。此外,与其他组相比,用CMBs处理后HRECs迁移和发育的抑制及抗血管生成作用得到改善。CMBs组小鼠视网膜新生血管形成明显受到抑制,且内皮抑素-GFP在小鼠视网膜中的荧光强度显著高于其他组。

结论

该研究表明超声靶向破坏CMBs对抑制血管形成和视网膜新生血管发育均具有显著作用。

相似文献

1
Ultrasound-targeted cationic microbubble-mediated gene transfection and inhibition of retinal neovascularization.
Int J Ophthalmol. 2022 Jun 18;15(6):876-885. doi: 10.18240/ijo.2022.06.04. eCollection 2022.
4
Antiangiogenesis effects of endostatin in retinal neovascularization.
J Ocul Pharmacol Ther. 2013 Sep;29(7):619-26. doi: 10.1089/jop.2012.0225. Epub 2013 Apr 1.
8
9
LncRNA Promotes Apoptosis, Invasion, and Angiogenesis of Retinal Endothelial Cells in Retinopathy of Prematurity MiR-145-5p.
Front Med (Lausanne). 2022 Apr 4;9:803214. doi: 10.3389/fmed.2022.803214. eCollection 2022.

引用本文的文献

1
Genetic Engineered Ultrasound-Triggered Injectable Hydrogels for Promoting Bone Reconstruction.
Research (Wash D C). 2023 Sep 1;6:0221. doi: 10.34133/research.0221. eCollection 2023.
2
Microbubble-Assisted Ultrasound for Drug Delivery to the Retina in an Ex Vivo Eye Model.
Pharmaceutics. 2023 Apr 11;15(4):1220. doi: 10.3390/pharmaceutics15041220.

本文引用的文献

1
Ultrasound molecular imaging-guided tumor gene therapy through dual-targeted cationic microbubbles.
Biomater Sci. 2021 Apr 7;9(7):2454-2466. doi: 10.1039/d0bm01857k. Epub 2021 Feb 17.
2
Transcutaneous Ultrasound-Mediated Nonviral Gene Delivery to the Liver in a Porcine Model.
Mol Ther Methods Clin Dev. 2019 Jul 26;14:275-284. doi: 10.1016/j.omtm.2019.07.005. eCollection 2019 Sep 13.
3
Control of Acoustic Cavitation for Efficient Sonoporation with Phase-Shift Nanoemulsions.
Ultrasound Med Biol. 2019 Mar;45(3):846-858. doi: 10.1016/j.ultrasmedbio.2018.12.001. Epub 2019 Jan 11.
4
Ultrasound-Mediated Gene Therapy in Swine Livers Using Single-Element, Multi-lensed, High-Intensity Ultrasound Transducers.
Mol Ther Methods Clin Dev. 2018 Jul 5;10:179-188. doi: 10.1016/j.omtm.2018.06.008. eCollection 2018 Sep 21.
6
Mechanistic understanding the bioeffects of ultrasound-driven microbubbles to enhance macromolecule delivery.
J Control Release. 2018 Feb 28;272:169-181. doi: 10.1016/j.jconrel.2018.01.001. Epub 2018 Jan 4.
7
Cationic gas-filled microbubbles for ultrasound-based nucleic acids delivery.
Biosci Rep. 2017 Dec 22;37(6). doi: 10.1042/BSR20160619.
8
Immunohistochemical Study of the Expression of Vascular Endothelial Growth Factor Receptor-2 (KDR/Flk-1) during Myocardial Infarction.
Bull Exp Biol Med. 2017 Aug;163(4):500-505. doi: 10.1007/s10517-017-3838-3. Epub 2017 Aug 29.
9
Cationic microbubbles and antibiotic-free miniplasmid for sustained ultrasound-mediated transgene expression in liver.
J Control Release. 2017 Sep 28;262:170-181. doi: 10.1016/j.jconrel.2017.07.015. Epub 2017 Jul 11.
10
Prospect of ultrasound-mediated gene delivery in cardiovascular applications.
Expert Opin Biol Ther. 2016 Jun;16(6):815-26. doi: 10.1517/14712598.2016.1169268. Epub 2016 Apr 11.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验