通过超声介导的微气泡破坏递送的Caveolin阻止内皮细胞增殖。

IF 2.3 4区 医学 Q3 BIOPHYSICS
Cellular and molecular bioengineering Pub Date : 2023-04-12 eCollection Date: 2023-06-01 DOI:10.1007/s12195-023-00763-1
Iván M López-Rodulfo, Elisa Villa-Martínez, Amelia Rios, Bruno Escalante
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引用次数: 0

摘要

引言:一氧化氮合酶(eNOS)是血管稳态的重要调节因子。eNOS由细胞内机制调节,包括与Caveolin-1(Cav)的蛋白质-蛋白质相互作用。Cav与eNOS结合并损害eNOS的激活,从而降低血管通透性和血管生成。Cav阻断eNOS已被认为是一种治疗性抗血管生成的方法。然而,需要解决肽的有效和可控递送。方法:用DAF2-DA评价触角(AP)-Cav在微泡(MBs)中的NO产生、用伤口愈合测定法评价细胞迁移、用BrdU评价细胞增殖和大鼠主动脉环离体血管生成。结果:AP-Cav对UMMD处理的细胞有增强的抑制作用。与游离AP Cav给药相比,MBs和AP Cav的超声破坏递送增加了乙酰胆碱诱导的bEnd.3细胞的NO释放、伤口愈合、细胞增殖和血管生成抑制。结论:我们证明,通过AP-Cav负载的MBs和UMMD递送Cav可能是一种通过提高疗效和细胞特异性来增加其治疗潜力的Cav给药方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Caveolin Delivered by Ultrasound-Mediated Microbubble Destruction Prevents Endothelial Cell Proliferation.

Caveolin Delivered by Ultrasound-Mediated Microbubble Destruction Prevents Endothelial Cell Proliferation.

Introduction: The nitric oxide synthase (eNOS) is an important regulator of vascular homeostasis. eNOS is modulated by intracellular mechanisms that include protein-protein interaction with Caveolin-1 (Cav). Cav binds to and impairs eNOS activation reducing vascular permeability and angiogenesis. Blocking of eNOS by Cav has been proposed as therapeutic antiangiogenic approach. However, the efficient and controlled delivery of the peptide requires to be solved.

Methods: The effect of antennapedia (AP)-Cav loaded into microbubbles (MBs) and delivered by ultrasound-mediated microbubble destruction (UMMD) into brain endothelial cells (bEnd.3 cells) was evaluated on NO production using DAF2-DA, cell migration assessed by the wound healing assay, cell proliferation with BrdU, and ex-vivo angiogenesis in rat aortic rings.

Results: An enhanced inhibitory effect of AP-Cav was observed on cells treated with UMMD. MBs and ultrasound disruption delivery of AP-Cav increased acetylcholine-induced NO release, wound healing, cell proliferation, and angiogenesis inhibition on bEnd.3 cells, compared to free AP-Cav administration.

Conclusion: We demonstrated that the delivery of Cav via AP-Cav-loaded MBs and UMMD may be an administration method for Cav that would increase its therapeutic potential by enhancing efficacy and cellular specificity.

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来源期刊
CiteScore
5.60
自引率
3.60%
发文量
30
审稿时长
>12 weeks
期刊介绍: The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.
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