Ultrasound image-guided treatment of ischemia-reperfusion injury using argon microbubbles
超声图像引导氩气微泡治疗缺血再灌注损伤
基本信息
- 批准号:10415201
- 负责人:
- 金额:$ 8.13万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-01 至 2023-04-30
- 项目状态:已结题
- 来源:
- 关键词:1-Phosphatidylinositol 3-Kinase3-DimensionalAcousticsAcuteAnimal ModelAnimalsApplications GrantsArgonBiological AssayBiological MarkersBlood CirculationCASP3 geneCardiacCaspaseCell Culture TechniquesCell LineCell SurvivalCell membraneCellsCentrifugationClinicClinicalCollaborationsColloidsCytoprotective AgentDevelopmentEncapsulatedEngineeringEnsureEnvironmentExhibitsExposure toFormulationFutureGasesGlucoseGlutamate ReceptorGoalsHealthHeart ArrestHeart InjuriesHypoxiaIn VitroIncentivesInhalationInjuryKidneyLengthLipidsLiposomesLiteratureMeasuresMediatingMethodsMicrobubblesMicrofluidicsModelingMyocardial InfarctionNeuronal InjuryNeuronsNitric OxideNoble GasesOxidative StressOxygenPathway interactionsPediatric HospitalsPerfusionPhiladelphiaPhospholipidsPhysiologicalPreclinical TestingPreparationProductionPropertyProto-Oncogene Proteins c-aktProtocols documentationReperfusion InjuryReperfusion TherapyReportingResearchRestSignal PathwaySignal TransductionSiteSolubilitySonicationStrokeSystemTestingTherapeuticTherapeutic EffectTimeTissuesTranslatingTranslationsTraumatic Brain InjuryUltrasonographyUp-RegulationValidationWorkXenonaqueousbaseclinical applicationdeprivationdesigndisabilityearly phase clinical trialefficacy evaluationefficacy testingexperiencehypoxic ischemic injuryimage guidedimage guided therapyimprovedin vivoin vivo imaginginterfacialischemic injurymouse modelnon-invasive imagingpreventscale upside effectsimulationtheranosticstreatment effectultrasoundvalidation studies
项目摘要
The key health significance of this proposal involves the ultrasound-mediated, image-guided, localized treatment
of ischemia reperfusion injury (IRI) in neuronal and cardiac models using echogenic argon microbubbles
(ArMBs). There exist no clinically approved methods for treating damaged tissue after experiencing hypoxic
ischemic and reperfusion injuries such as stroke or cardiac arrest. Noble gases like argon (Ar) and xenon (Xe)
are highly promising cytoprotective agents that have been shown to successfully treat acute IRI in vitro and in
animal models. Whereas Xe has been researched in greater detail including in early clinical trials, it can be
prohibitively expensive and difficult to obtain. Ar is a hundred times cheaper and widely available, while exhibiting
excellent organoprotective efficiency. Furthermore, the mechanism of Xe action depends on its interaction with
glutamate receptors on cell membranes, whereas Ar is reported to work by stimulating various endogenous
cellular protecting signaling pathways, making it a more versatile antiapoptotic agent. Current Ar therapy is long
and systemic, via inhalation, making it non-specific to the injury site, likely diminishing therapeutic effect. As a
solution, we propose the development of MBs (MBs) for localized delivery of the therapeutic gas. MBs are
inherently echogenic due to their non-linear oscillations induced by clinical ultrasound. Therapeutic gases such
as Ar, however, are difficult to stabilize inside bubbles due to the former's high aqueous solubility. The team has
recently succeeded in small-scale production of stable, echogenic, noble gas MBs through optimization of the
MB shell composition, leading to a productive, ongoing collaboration with clinicians at the Children's Hospital of
Philadelphia (CHOP). The proposed research will be conducted through the implementation of three specific
aims. (1) 1-10 µm ArMBs will be formulated at a high yield of >1010 MBs per mL. Ultrasound signal of optimized
ArMBs will be investigated in flow phantoms and in a mouse model by measuring the magnitude, perfusion, and
persistence of contrast. (2) The therapeutic effect of ultrasound mediated Ar release from bubbles in treating IRI
will be estimated in in vitro cell culture-based simulations of neuronal and cardiac injuries induced by oxygen
glucose deprivation. The validity of ArMBs will be proved by enhanced cell viability, decrease in caspase
activation, and upregulation in the phosphatidylinositol 3 kinase (PI3K-AKT) pathway. (3) Further incentive to
use ArMBs will be recognized by comparing their IRI treatment results to that of bulk Ar exposure to cells and
exposure to XeMBs. ArMB activity even with the deactivation of glutamate receptors will be shown to cement
the feasibility of ArMBs for a variety of cytoprotective treatments. The PI team will leverage their expertise in
colloidal design, cellular dynamics, and ultrasound imaging to precisely engineer the ArMB shell and to rigorously
establish the validity of this new, inexpensive agent in vitro for the team's long-term goal of testing ArMBs for
non-invasive, image guided treatment of IRI in large animal models and translating them to clinical settings.
该建议的关键健康意义涉及超声介导,图像引导,局部治疗
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Daeyeon Lee其他文献
Daeyeon Lee的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Daeyeon Lee', 18)}}的其他基金
Ultrasound image-guided treatment of ischemia-reperfusion injury using argon microbubbles
超声图像引导氩气微泡治疗缺血再灌注损伤
- 批准号:
10303690 - 财政年份:2021
- 资助金额:
$ 8.13万 - 项目类别:
相似海外基金
REU Site: Design, Create, and Innovate 3-Dimensional User Interfaces to Improve Human Sensory and Motor Performance in Virtual Environments (HUMANS MOVE)
REU 网站:设计、创建和创新 3 维用户界面,以提高虚拟环境中的人类感官和运动表现 (HUMANS MOVE)
- 批准号:
2349771 - 财政年份:2024
- 资助金额:
$ 8.13万 - 项目类别:
Standard Grant
CAREER: Atomic-level understanding of stability and transition kinetics of 3-dimensional interfaces under irradiation
职业:对辐照下 3 维界面的稳定性和转变动力学的原子水平理解
- 批准号:
2340085 - 财政年份:2024
- 资助金额:
$ 8.13万 - 项目类别:
Continuing Grant
Artificial fabrication of 3-dimensional noncollinear magnetic order and magnetization manipulation by spin torque
三维非共线磁序的人工制造和自旋转矩磁化操纵
- 批准号:
23H00232 - 财政年份:2023
- 资助金额:
$ 8.13万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Understanding of 3-dimensional seismic behavior of RC frame high-speed railway/highway viaducts using FE analysis
使用有限元分析了解 RC 框架高速铁路/公路高架桥的 3 维抗震性能
- 批准号:
23H01489 - 财政年份:2023
- 资助金额:
$ 8.13万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Modernization of 3-dimensional printing capabilities at the Aquatic Germplasm and Genetic Resource Center
水产种质和遗传资源中心 3 维打印能力的现代化
- 批准号:
10736961 - 财政年份:2023
- 资助金额:
$ 8.13万 - 项目类别:
The 3-dimensional nest of the honey bee: organization, development, and impact on colony function
蜜蜂的 3 维巢穴:组织、发育及其对蜂群功能的影响
- 批准号:
2216835 - 财政年份:2023
- 资助金额:
$ 8.13万 - 项目类别:
Standard Grant
Research on high-density 3-dimensional polymer optical waveguide device for photonics-electronics convergence
光电子融合高密度三维聚合物光波导器件研究
- 批准号:
23H01882 - 财政年份:2023
- 资助金额:
$ 8.13万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Scaff-Net: 3 Dimensional multiphoton polymerisation printed scaffolds for medium throughput recording from stem cell derived human cortical networks.
Scaff-Net:3 维多光子聚合打印支架,用于从干细胞衍生的人类皮质网络进行中等通量记录。
- 批准号:
EP/X018385/1 - 财政年份:2023
- 资助金额:
$ 8.13万 - 项目类别:
Research Grant
3-dimensional prompt gamma imaging for online proton beam dose verification
用于在线质子束剂量验证的 3 维瞬发伽马成像
- 批准号:
10635210 - 财政年份:2023
- 资助金额:
$ 8.13万 - 项目类别:
Equipment: MRI: Track 1 Acquisition of a 3-Dimensional Nanolithography Instrument
设备:MRI:轨道 1 获取 3 维纳米光刻仪器
- 批准号:
2320636 - 财政年份:2023
- 资助金额:
$ 8.13万 - 项目类别:
Standard Grant