Magnetic nanoparticles assisted modulation of the vascular cGMP system

磁性纳米颗粒辅助调节血管 cGMP 系统

• 批准号: 114073527
• 负责人: Professor Dr. Alexander Pfeifer
• 金额: --
• 依托单位: Institut für Pharmakologie und Toxikologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/114073527?language=en
• 关键词: Magnetic; nanoparticles; assisted; modulation; vascular

In the first funding period, we focused on the use of magnetic nanoparticles (MNPs) to enhance and target lentiviral (LV) gene transfer in the vascular system. A broad spectrum of MNPs was studied to optimize LV gene transfer in vitro and ex vivo. In addition, first studies in vivo were performed. Based on this work, we will now focus on the study of the nitric oxide (NO)/cGMP pathway, which is essential for vascular homeostasis. In the present proposal, we will study novel mechanisms that control NO and cGMP production. The major focus will be on cGMP-dependent protein kinase (protein kinase G, PKG) and its downstream targets that mediate the NO/cGMP/PKG effects. We have preliminary data suggesting that a so far unknown pathway involving a PKG substrate and the small GTPase Rac regulate cellular cGMP concentrations. Moreover, we will study the link between cGMP/PKG signaling and NO production in the endothelium. Without the application of MNPs and magnetic gradient field an efficient and targeted transduction of vessels under flow conditions is not possible. Therefore, we will use optimized LV/MNP complexes to study the physiological effects of the signaling pathways in the vascular system. Apart from ex vivo perfusion systems that also allow for force measurements as an important physiological read-out, we will further develop the LV/MNP system using MNP-containing microbubbles (MBs) with the aim to achieve efficient gene transfer to vessels in the vascular system in vivo.

在第一个资助期，我们专注于使用磁性纳米颗粒（MNP）来增强和靶向血管系统中的慢病毒（LV）基因转移。研究了广泛的 MNP 以优化体外和离体 LV 基因转移。此外，还进行了首次体内研究。基于这项工作，我们现在将重点研究一氧化氮 (NO)/cGMP 途径，这对于血管稳态至关重要。在本提案中，我们将研究控制 NO 和 cGMP 产生的新机制。主要重点是 cGMP 依赖性蛋白激酶（蛋白激酶 G、PKG）及其介导 NO/cGMP/PKG 效应的下游靶标。我们的初步数据表明，迄今为止未知的途径涉及 PKG 底物和小 GTPase Rac 调节细胞 cGMP 浓度。此外，我们将研究 cGMP/PKG 信号传导与内皮细胞中 NO 产生之间的联系。如果不应用 MNP 和磁梯度场，就不可能在流动条件下对血管进行有效且有针对性的转导。因此，我们将使用优化的LV/MNP复合物来研究血管系统中信号通路的生理效应。除了还可以将力测量作为重要生理读数的离体灌注系统外，我们将进一步开发使用含有 MNP 的微泡 (MB) 的 LV/MNP 系统，旨在实现体内血管系统中血管的有效基因转移。

项目成果

Optimization of Magnetic Nanoparticle-Assisted Lentiviral Gene Transfer

• DOI: 10.1007/s11095-011-0660-x
• 发表时间: 2012-01
• 期刊: Pharmaceutical Research
• 影响因子: 3.7
• 作者: Christina Trueck;Katrin Zimmermann;O. Mykhaylyk;M. Anton;Sarah Vosen;D. Wenzel;B. Fleischmann;A. Pfeifer

Magnetic Nanoparticles for Biomedical Applications

• DOI: 10.1007/s11095-012-0736-2
• 发表时间: 2012-03
• 期刊: Pharmaceutical Research
• 影响因子: 3.7
• 作者: A. Pfeifer;Katrin Zimmermann;C. Plank

Combined targeting of lentiviral vectors and positioning of transduced cells by magnetic nanoparticles

• DOI: 10.1073/pnas.0803746106
• 发表时间: 2009-01-06
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Hofmann, Andreas;Wenzel, Daniela;Pfeifer, Alexander
• 通讯作者: Pfeifer, Alexander

Vascular Repair by Circumferential Cell Therapy Using Magnetic Nanoparticles and Tailored Magnets.

• DOI: 10.1021/acsnano.5b04996
• 发表时间: 2016-01
• 期刊: ACS nano
• 影响因子: 17.1
• 作者: Sarah Vosen;S. Rieck;Alexandra Heidsieck;O. Mykhaylyk;Katrin Zimmermann;W. Bloch;D. Eberbeck;C. Plank;B. Gleich;A. Pfeifer;B. Fleischmann;D. Wenzel

Identification of Magnetic Nanoparticles for Combined Positioning and Lentiviral Transduction of Endothelial Cells

用于内皮细胞组合定位和慢病毒转导的磁性纳米颗粒的鉴定

• DOI: 10.1007/s11095-011-0657-5
• 发表时间: 2012
• 期刊: Pharmaceutical Research
• 影响因子: 3.7
• 作者: Wenzel D;Rieck S;Vosen S;Mykhaylyk O;Trueck C;Eberbeck D;Trahms L;Zimmermann K;Pfeifer A;Fleischmann BK
• 通讯作者: Fleischmann BK