Chemical, Structural, and Superstructural Determinants of Nanocarbon Toxicity
纳米碳毒性的化学、结构和上层结构决定因素
基本信息
- 批准号:7341336
- 负责人:
- 金额:$ 38.1万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-09-20 至 2011-05-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAdsorptionAnimal TestingAreaAsbestosBioavailableBiologicalBiological AssayBiological AvailabilityBiological ModelsBreathingCaliberCarbonCarbon NanotubesCellsCellular AssayChargeChemicalsChemistryChronicClassificationComplexComputer Systems DevelopmentConflict (Psychology)Cultured CellsDevelopmentDevicesDimensionsDrug Delivery SystemsElasticityEnd PointEnvironmentEnvironmental ExposureExposure toFibrosisFullerenesGranulomaHandHealthHousingHumanHydrophobicityIn VitroInflammationInjuryInterdisciplinary StudyLengthLungMacrophage ActivationMediator of activation proteinMetalsMethodsModelingMolecularMolecular ProfilingMorphologyMovementNanotechnologyNanotubesNeuronsOccupationalOsteoblastsOxidantsOxidation-ReductionPathologicPathologistPopulationPriceProcessProductionPropertyReactionReference StandardsRelative (related person)RiskRodentRoleScientistScreening procedureSepharoseShapesSimulateSite-Directed MutagenesisStressSurfaceTechniquesTestingTissuesToxic effectToxicologyTubeUniversitiesWorkbasebiomaterial compatibilitycatalystchemical propertycommercial applicationcommercializationcostcytokinecytotoxicitydesignin vivoinnovationinterstitiallung injurynanofibernanomaterialsnanoscalenanotoxicologynovelphysical propertyresponsesizetool
项目摘要
DESCRIPTION (provided by applicant)
Adverse human health effects due to occupational and environmental exposure to nanomaterials are a major concern and a potential threat to their successful commercialization and biomedical applications. Realization of their commercial potential will require a better understanding of the interactions of nanomaterials with biological systems and the development of new strategies to manage human health risk. Manufactured carbon nanomaterials are highly variable with respect to chemical and physical properties, state of aggregation, and purity. Toxicological screening is urgently needed to identify potentially hazardous nanomaterials; however, their wide variability and unique properties complicate interpretation of traditional in vitro and in vivo toxicity assays. An interdisciplinary research team at Brown University including a materials scientist, a toxicologic pathologist, and a molecular biologist has developed a panel of novel nanomaterials and innovative approaches for nanotoxicology assays. This panel of model nanomaterials will be expanded to include selected commercial materials subjected to rigorous characterization of lexicologically relevant materials properties. Novel synthesis and characterization methods will be used to carry out systematic studies (Specific Aims 1 and 2) that reveal the chemical (surface state, metals bioavailability, biopersistence), structural (size, shape, elasticity), and superstructural (aggregate size and shape) basis of carbon nanomaterial toxicity. This team will develop and validate a unique platform for cellular assays in 3- dimensional culture using formation of granulomas, persistent macrophage activation, and fibrosis as pathologic endpoints (Specific Aim 3). This platform will incorporate post-exposure characterization of nanomaterials in parallel with an acellular assay to assess biopersistence and aggregation state in simulated intracellular environments (Specific Aim 4). A cytokine expression profile will be developed to predict toxicity of carbon nanomaterials relative to standard reference materials (Specific Aim 5). It is anticipated that this validated toxicologic screening assay will provide an alternative to chronic rodent inhalation assays at lower cost and reduced burden of animal testing. Identification of specific chemical and physical properties of nanomaterials responsible for cellular toxicity will enable development of manufacturing methods and post processing steps to eliminate intrinsic toxicity.
描述(由申请人提供)
由于职业和环境接触纳米材料而对人类健康产生的不利影响是一个主要问题,也是对其成功商业化和生物医学应用的潜在威胁。实现其商业潜力将需要更好地了解纳米材料与生物系统的相互作用,并制定新的战略来管理人类健康风险。人造碳纳米材料在化学和物理性质、聚集状态和纯度方面变化很大。迫切需要进行毒理学筛选,以确定潜在的危险纳米材料;然而,其广泛的变异性和独特的性质使传统的体外和体内毒性测定的解释复杂化。布朗大学的一个跨学科研究小组,包括一名材料科学家,一名毒理学病理学家和一名分子生物学家,已经开发了一组新型纳米材料和创新的纳米毒理学检测方法。这一小组的模型纳米材料将扩大到包括选定的商业材料进行严格的表征词汇相关的材料性能。新的合成和表征方法将用于进行系统研究(具体目标1和2),揭示碳纳米材料毒性的化学(表面状态,金属生物利用度,生物持久性),结构(大小,形状,弹性)和超结构(聚集体大小和形状)基础。该团队将开发和验证一个独特的平台,用于三维培养中的细胞测定,使用肉芽肿形成、持续巨噬细胞活化和纤维化作为病理终点(具体目标3)。该平台将结合纳米材料的暴露后表征,同时进行无细胞测定,以评估模拟细胞内环境中的生物持久性和聚集状态(具体目标4)。将开发细胞因子表达谱,以预测碳纳米材料相对于标准参考材料的毒性(具体目标5)。预计这种经验证的毒理学筛选试验将以较低的成本和减轻的动物试验负担提供慢性啮齿动物吸入试验的替代方法。确定导致细胞毒性的纳米材料的特定化学和物理性质将有助于开发制造方法和后处理步骤,以消除内在毒性。
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('Agnes B Kane', 18)}}的其他基金
Chemical, Structural, and Superstructural Determinants of Nanocarbon Toxicity
纳米碳毒性的化学、结构和上层结构决定因素
- 批准号:
7814469 - 财政年份:2009
- 资助金额:
$ 38.1万 - 项目类别:
Chemical, Structural, and Superstructural Determinants of Nanocarbon Toxicity
纳米碳毒性的化学、结构和上层结构决定因素
- 批准号:
7625054 - 财政年份:2007
- 资助金额:
$ 38.1万 - 项目类别:
Chemical, Structural, and Superstructural Determinants of Nanocarbon Toxicity
纳米碳毒性的化学、结构和上层结构决定因素
- 批准号:
7498514 - 财政年份:2007
- 资助金额:
$ 38.1万 - 项目类别:
PLEURAL DOSIMETRY AND BIOMARKERS OF RESPONSE TO FIBERS
胸膜剂量测定和纤维反应的生物标志物
- 批准号:
2154543 - 财政年份:1992
- 资助金额:
$ 38.1万 - 项目类别:
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