Nanomedical approach to prevention and treatment of atherosclerosis

预防和治疗动脉粥样硬化的纳米医学方法

• 批准号: 243858656
• 负责人: Professorin Dr. Iwona Cicha, Ph.D.
• 金额: --
• 依托单位: Sektion für Experimentelle Onkologie und Nanomedizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/243858656?language=en
• 关键词: Nanomedical; approach; prevention; treatment; atherosclerosis

Cardiovascular diseases represent one of the biggest global healthproblems, but effective approaches to targeted therapies are stillmissing. The potential clinical impact of nanotechnology in terms ofcardiovascular diseases management is enormous, but no specificnanoparticle-based system has been approved for diagnosis ortherapy of atherosclerosis in humans. In the field of atherosclerosis,magnetic targeting of SPION-loaded cells to vascular stents in orderto prevent thrombosis and restenosis constitutes a promisingpreclinical approach. However, the experimental attempts tomagnetically target drugs to medium and large vessels are veryscarce. Consequently, little is known about the feasibility of magneticdrug targeting approach in atherosclerosis. In the original project, weanalyzed the direct in vitro effect of SPIONs on endothelium,investigated the magnetic targeting of SPIONs using human arteriesex vivo, and established angiography-aided in vivo targeting ofSPIONs in rabbit model. Further, we evaluated the effects of SPIONsconjugated with dexamethasone on atherosclerotic plaques in a rabbitmodel of abdominal aortic atherosclerosis. In this renewal project, wepropose to focus our investigations on magnetic drug targetingapproach to atherosclerosis in order to validate the feasibility ofregion-specific SPION accumulation ex vivo and in vivo. Furthermore,the therapeutic efficacy of the drug-conjugated SPIONs will beextensively investigated in a rabbit model of advancedatherosclerosis. To achieve these objectives, we will at first analysethe effects of blood components on magnetic particle accumulationunder flow ex vivo. The further tasks will be designed to achieve an invivo proof of efficacy studies on magnetic particle accumulation anddrug targeting using drug-loaded SPIONs. For this purpose, we willevaluate the efficacy of SPION delivery to atherosclerotic plaquesusing magnetic resonance imaging and histology. Furthermore, toobtain the preclinical proof of efficacy of the previously developedmarimastat-bound SPIONs and anti-VEGF antibody-conjugatedSPIONs, the magnetic drug targeting studies in atherosclerotic rabbitswill be performed using these nanoparticles. We are convinced thatby increasing the effective local doses of pharmaceutical agents,magnetic drug targeting may represent a useful tool to improve theplaque stability and reduce inflammatory responses.

心血管疾病是全球最大的健康问题之一，但仍然缺乏有效的靶向治疗方法。纳米技术在心血管疾病管理方面的潜在临床影响是巨大的，但是没有特定的基于纳米颗粒的系统被批准用于诊断或治疗人类动脉粥样硬化。在动脉粥样硬化领域，磁靶向SPION负载细胞的血管支架，以防止血栓形成和再狭窄构成了一个有前途的临床前方法。然而，磁靶向药物在中、大血管中的实验研究还很少。因此，磁靶向药物治疗动脉粥样硬化的可行性尚不清楚.本课题首先分析了SPIONs对血管内皮的直接体外作用，然后研究了SPIONs的磁靶向作用，最后建立了血管造影辅助的SPIONs体内靶向作用的兔模型。此外，我们评估了SPION与地塞米松结合对兔腹主动脉粥样硬化模型中动脉粥样硬化斑块的影响。在这个更新的项目中，我们建议将我们的研究重点放在磁药物靶向动脉粥样硬化的方法，以验证区域特异性SPION积累的可行性离体和体内。此外，药物结合SPION的治疗效果将在兔晚期动脉粥样硬化模型中进行广泛研究。为了实现这些目标，我们将首先分析血液成分对离体流动条件下磁性颗粒积聚的影响。进一步的任务将被设计为使用载药SPION实现关于磁性颗粒积聚和药物靶向的有效性研究的体内证明。为此，我们将通过磁共振成像和组织学评价SPION对动脉粥样硬化斑块的疗效。此外，为了获得先前开发的马立马司他结合SPION和抗VEGF抗体缀合SPION的临床前疗效证据，将使用这些纳米颗粒在动脉粥样硬化兔中进行磁性药物靶向研究。我们相信，通过增加药物的有效局部剂量，磁性药物靶向可能是改善斑块稳定性和减少炎症反应的有用工具。

项目成果

Drug delivery to atherosclerotic plaques using superparamagnetic iron oxide nanoparticles

• DOI: 10.2147/ijn.s179273
• 发表时间: 2018-01-01
• 期刊: INTERNATIONAL JOURNAL OF NANOMEDICINE
• 影响因子: 8
• 作者: Matuszak，Jasmin;Lutz，Barbara;Cicha，Iwona
• 通讯作者: Cicha，Iwona

Magnetic Accumulation of SPIONs under Arterial Flow Conditions: Effect of Serum and Red Blood Cells

• DOI: 10.3390/molecules24142588
• 发表时间: 2019-07-02
• 期刊: MOLECULES
• 影响因子: 4.6
• 作者: Hennig, Till L.;Unterweger, Harald;Cicha, Iwona
• 通讯作者: Cicha, Iwona

Endothelial biocompatibility and accumulation of SPION under flow conditions

流动条件下内皮生物相容性和 SPION 的积累

• DOI: 10.1016/j.jmmm.2014.09.005
• 发表时间: 2015
• 期刊: Journal of Magnetism and Magnetic Materials
• 影响因子: 2.7
• 作者: Matuszak J;Zaloga J;Friedrich RP;Lyer S;Nowak J;Odenbach S;Alexiou C;Cicha I
• 通讯作者: Cicha I