NANOFORMULATIONS OF REDOX ENZYMES FOR TREATMENT OF ISCHEMIC STROKE
用于治疗缺血性中风的氧化还原酶纳米制剂
基本信息
- 批准号:8360237
- 负责人:
- 金额:$ 22.31万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-07-01 至 2012-06-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAttenuatedBiologicalBlood - brain barrier anatomyBlood CirculationBlood flowBrainBrain HypoxiaCell SurvivalCentral Nervous System DiseasesChargeComplexEndothelial CellsEnzymesFree Radical ScavengersFundingGrantIn VitroInflammationIschemic StrokeMicellesModelingNational Center for Research ResourcesNebraskaOxidation-ReductionPatientsPermeabilityPhasePhysiologicalPrincipal InvestigatorResearchResearch InfrastructureResourcesSourceStagingStrokeSystemTherapeuticTimeUnited States National Institutes of Healthcatalasecostcrosslinkenzyme activityimprovedin vivonano containernanoformulationnanomedicineneuroinflammationneuroprotectionnovelpolyionpolypeptideregenerative therapyrestorationtherapeutic protein
项目摘要
This subproject is one of many research subprojects utilizing the resources
provided by a Center grant funded by NIH/NCRR. Primary support for the subproject
and the subproject's principal investigator may have been provided by other sources,
including other NIH sources. The Total Cost listed for the subproject likely
represents the estimated amount of Center infrastructure utilized by the subproject,
not direct funding provided by the NCRR grant to the subproject or subproject staff.
The long-term objective of this proposal is to develop delivery system of free-radical scavengers, RedOx enzymes, to the brain to attenuate neuroinflammation and increase neuroprotection in patients with ischemic stroke. Initial treatment for stroke involves removing the blockage and restoring blood flow. When acute phase is over, the treatment focused on restoration of brain function and cell survival. At this stage, delivery of RedOx enzymes to the brain to decrease inflammation is of great importance. However, the blood brain barrier (BBB) severely limits the delivery of therapeutic polypeptides to the brain and is a major obstacle to the successful treatment of many devastating central nervous system (CNS) diseases. To improve the therapeutic polypeptide transport to the brain, preserve enzyme activity, and reduce immunogenecity, the therapeutic RedOx enzymes will be cross-linked with a synthetic polyelectrolyte of opposite charge to form a stable polyion complex micelle, "nanozyme". We hypothesize that 1) enzyme incorporated nanocontainers will be stable at physiological conditions, 2) will enhance permeability of the enzyme across the in vitro BBB, 3) will increase circulation time and/or permeability across the BBB in vivo, and 4) will improve biological activity in in vitro brain hypoxia and in vivo stroke models. Specific Aims are 1) to assemble RedOx nanozymes (SOD, catalase) and tailor the composition for increased stability, circulation time and/or permeability across the BBB, 2) to determine permeability and transport mechanisms of the nanozymes synthesized in SA1 across the brain microvascular endothelial cells (BMVEC) in vitro and in vivo, 3) to determine whether the most promising nanozymes selected in SA2 can attenuate neuroinflammation and provide neuroprotection in an in vitro brain hypoxia and in vivo stroke models. It is anticipated that these studies will provide a novel platform for the delivery of therapeutic proteins across the BBB for regenerative therapy.
该子项目是利用资源的众多研究子项目之一
由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持
并且子项目的主要研究者可能是由其他来源提供的,
包括其他 NIH 来源。 子项目可能列出的总成本
代表子项目使用的中心基础设施的估计数量,
NCRR 赠款不直接向子项目或子项目工作人员提供资金。
该提案的长期目标是开发自由基清除剂 RedOx 酶的递送系统,以减轻缺血性中风患者的神经炎症并增强神经保护。中风的初始治疗包括消除阻塞和恢复血流。急性期结束后,治疗重点是恢复脑功能和细胞存活。在此阶段,将氧化还原酶输送到大脑以减少炎症非常重要。然而,血脑屏障(BBB)严重限制了治疗性多肽向大脑的递送,并且是成功治疗许多破坏性中枢神经系统(CNS)疾病的主要障碍。为了改善治疗性多肽向大脑的转运、保持酶活性并降低免疫原性,治疗性 RedOx 酶将与具有相反电荷的合成聚电解质交联,形成稳定的聚离子复合胶束,即“纳米酶”。我们假设:1)掺入酶的纳米容器在生理条件下是稳定的,2)将增强酶穿过体外血脑屏障的渗透性,3)将增加体内血脑屏障的循环时间和/或渗透性,4)将改善体外脑缺氧和体内中风模型的生物活性。具体目标是 1) 组装 RedOx 纳米酶(SOD、过氧化氢酶)并定制组合物,以提高稳定性、循环时间和/或穿过 BBB 的渗透性,2) 确定 SA1 中合成的纳米酶在体外和体内穿过脑微血管内皮细胞 (BMVEC) 的渗透性和转运机制,3) 确定是否最有希望 SA2 中选择的纳米酶可以减轻神经炎症,并在体外脑缺氧和体内中风模型中提供神经保护。预计这些研究将为跨血脑屏障递送治疗蛋白进行再生治疗提供一个新的平台。
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)
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{{ truncateString('ELENA BATRAKOVA', 18)}}的其他基金
Extracellular Vesicles for CNS Delivery of Therapeutic Enzymes to Treat Lysosomal Storage Disorders
细胞外囊泡用于中枢神经系统递送治疗酶以治疗溶酶体贮积症
- 批准号:
10436223 - 财政年份:2019
- 资助金额:
$ 22.31万 - 项目类别:
Extracellular Vesicles for CNS Delivery of Therapeutic Enzymes to Treat Lysosomal Storage Disorders
细胞外囊泡用于中枢神经系统递送治疗酶以治疗溶酶体贮积症
- 批准号:
10650176 - 财政年份:2019
- 资助金额:
$ 22.31万 - 项目类别:
Extracellular Vesicles for CNS Delivery of Therapeutic Enzymes to Treat Lysosomal Storage Disorders
细胞外囊泡用于中枢神经系统递送治疗酶以治疗溶酶体贮积症
- 批准号:
10005970 - 财政年份:2019
- 资助金额:
$ 22.31万 - 项目类别:
Extracellular Vesicles for CNS Delivery of Therapeutic Enzymes to Treat Lysosomal Storage Disorders
细胞外囊泡用于中枢神经系统递送治疗酶以治疗溶酶体贮积症
- 批准号:
9768769 - 财政年份:2019
- 资助金额:
$ 22.31万 - 项目类别:
Extracellular Vesicles for CNS Delivery of Therapeutic Enzymes to Treat Lysosomal Storage Disorders
细胞外囊泡用于中枢神经系统递送治疗酶以治疗溶酶体贮积症
- 批准号:
10213863 - 财政年份:2019
- 资助金额:
$ 22.31万 - 项目类别:
Cell-based Platform for Gene Delivery to the Brain
基于细胞的基因传递至大脑的平台
- 批准号:
10333329 - 财政年份:2018
- 资助金额:
$ 22.31万 - 项目类别:
NANOFORMULATIONS OF REDOX ENZYMES FOR TREATMENT OF ISCHEMIC STROKE
用于治疗缺血性中风的氧化还原酶纳米制剂
- 批准号:
8167875 - 财政年份:2010
- 资助金额:
$ 22.31万 - 项目类别:
NANOFORMULATIONS OF REDOX ENZYMES FOR TREATMENT OF ISCHEMIC STROKE
用于治疗缺血性中风的氧化还原酶纳米制剂
- 批准号:
7960469 - 财政年份:2009
- 资助金额:
$ 22.31万 - 项目类别:
Inflammatory Cells for Transport of Therapeutic Polypeptides Across the BBB
用于跨 BBB 运输治疗性多肽的炎症细胞
- 批准号:
8134749 - 财政年份:2008
- 资助金额:
$ 22.31万 - 项目类别:
Inflammatory Cells for Transport of Therapeutic Polypeptides Across the BBB
用于跨 BBB 运输治疗性多肽的炎症细胞
- 批准号:
8329677 - 财政年份:2008
- 资助金额:
$ 22.31万 - 项目类别:
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