Gene Delivery Nanoparticles to Treat Glioblastoma
基因递送纳米颗粒治疗胶质母细胞瘤
基本信息
- 批准号:10304144
- 负责人:
- 金额:$ 35.76万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-12-16 至 2023-11-30
- 项目状态:已结题
- 来源:
- 关键词:AffectAnimal Cancer ModelAstrocytesBiologicalBiological ModelsBiomedical EngineeringBiotechnologyBrainCancer ModelCationsCellsCerebrospinal FluidClinicClinicalConvectionCytosolDNA deliveryDevelopmentDiseaseDrug resistanceElectrostaticsEndosomesEngineeringEpigenetic ProcessEvaluationFormulationGene DeliveryGlioblastomaHealthHumanIn VitroLabelMalignant NeoplasmsMalignant neoplasm of brainMessenger RNAMicroRNAsMicrogliaModelingMolecularNuclearPharmaceutical PreparationsPolymersPropertyRadiationRegenerative MedicineResearch ProposalsRodRodentRodent ModelRoleSafetySiteSpecificityStructureSurfaceTechnologyTherapeuticTimeTranslatingUntranslated RNAbrain cellcancer cellcancer stem cellcancer therapycell typechemical propertychemotherapycrosslinkcytotoxicitydesignextracellularflexibilitygenetic technologyhuman diseasein vivoinnovative technologiesinterestnanobiotechnologynanoparticlenanoparticle deliverynervous system disorderneuroregulationnovelnovel therapeuticsparticlephysical propertyplasmid DNAradiation resistancestandard of carestem cell biologystem cellstechnology validationtemozolomidetherapeutically effectivetumoruptake
项目摘要
There is a need to create new biotechnology to safely and effectively deliver miRNA to target cells
of interest in the brain. We propose to develop enhanced polymeric nanoparticles designed to be
stable extracellularly and bioreducible intracellularly, to enable safe and effective delivery of
miRNA. We will validate these particles in models of brain cancer as it is a deadly disease that
is in critical need of new therapies. In particular, we will evaluate treatment of human
glioblastoma in orthotopic models compared to the standard of care. Polymer structures will be
synthesized and utilized to fabricate non-viral nanoparticles for delivery to multiple brain cell
types including healthy cells and cancer cells. Nanoparticle formulations will be developed that
remain stable in cerebrospinal fluid (CSF) and that can spread throughout the brain following
administration by convection-enhanced delivery (CED). We will investigate novel miRNA drugs
capable of overcoming known drug and radiation resistances by targeting tumor-propagating brain
cancer stem cells (BCSCs). Novel miRNA combinations will be evaluated in vitro and in vivo. The
nanoparticles will be tracked to evaluate their intracellular and extracellular delivery and cell
specificity. Transport and safety through normal and tumor- bearing rodent brains following CED
will be analyzed. Leading nanoparticles will be evaluated in an orthotopic model for human
glioblastoma using molecular and cell biological endpoints and anti-tumor efficacy will be compared
to the standard of care as well as in combination with the standard of care. We will create an
innovative technology for miRNA delivery and validate it in models of brain cancer.
需要创造新的生物技术来安全有效地将miRNA递送到靶细胞
对大脑的兴趣。我们建议开发增强的聚合物纳米颗粒,
细胞外稳定和细胞内生物可还原,从而能够安全有效地递送
小RNA。 我们将在脑癌模型中验证这些粒子,因为它是一种致命的疾病,
急需新的疗法 特别是,我们将评估人类的治疗
与标准治疗相比,原位模型中的胶质母细胞瘤。 聚合物结构将是
合成并用于制造用于递送到多个脑细胞非病毒纳米颗粒
包括健康细胞和癌细胞。将开发纳米颗粒制剂,
在脑脊液(CSF)中保持稳定,并可在
通过对流增强输送(CED)给药。 我们将研究新的miRNA药物,
能够通过靶向肿瘤传播的脑来克服已知的药物和放射抗性,
癌症干细胞(BCSC)。 新的miRNA组合将在体外和体内进行评估。的
纳米颗粒将被跟踪,以评估它们的细胞内和细胞外递送和细胞内递送。
的特异性 CED后通过正常和荷瘤啮齿动物脑的转运和安全性
将被分析。 将在人体原位模型中评价先导纳米颗粒
将使用分子和细胞生物学终点和抗肿瘤疗效对胶质母细胞瘤进行比较
标准治疗以及与标准治疗相结合。我们将创建一个
miRNA递送的创新技术,并在脑癌模型中验证它。
项目成果
期刊论文数量(0)
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Jordan Green其他文献
Jordan Green的其他文献
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{{ truncateString('Jordan Green', 18)}}的其他基金
Kinetic Assembly of Polymer-mRNA Nanoparticles Targets Circulating Monocytes to Enhance Cancer Immunotherapy
聚合物-mRNA纳米颗粒的动力学组装靶向循环单核细胞以增强癌症免疫治疗
- 批准号:
10681055 - 财政年份:2023
- 资助金额:
$ 35.76万 - 项目类别:
A Non-Viral Genetic Vaccine for Prevention and Treatment of Multiple Sclerosis
用于预防和治疗多发性硬化症的非病毒基因疫苗
- 批准号:
10374165 - 财政年份:2021
- 资助金额:
$ 35.76万 - 项目类别:
A Non-Viral Genetic Vaccine for Prevention and Treatment of Multiple Sclerosis
用于预防和治疗多发性硬化症的非病毒基因疫苗
- 批准号:
10228440 - 财政年份:2021
- 资助金额:
$ 35.76万 - 项目类别:
Gene Delivery Nanoparticles to Treat Glioblastoma
基因递送纳米颗粒治疗胶质母细胞瘤
- 批准号:
10058249 - 财政年份:2018
- 资助金额:
$ 35.76万 - 项目类别:
Gene Delivery Nanoparticles to Treat Glioblastoma
基因递送纳米颗粒治疗胶质母细胞瘤
- 批准号:
10532146 - 财政年份:2018
- 资助金额:
$ 35.76万 - 项目类别:
Nanoparticle Modified Human Fat Derived Mesenchymal Stem Cells for Brain Cancer (Change of Organization Application)
纳米颗粒修饰的人类脂肪源性间充质干细胞治疗脑癌(组织申请变更)
- 批准号:
9551197 - 财政年份:2017
- 资助金额:
$ 35.76万 - 项目类别: