Sytems Analysis of Nanoparticle Biocompatibility
纳米粒子生物相容性的系统分析
基本信息
- 批准号:7341333
- 负责人:
- 金额:$ 47.13万
- 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:2007-09-17 至 2011-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAdverse effectsAnimalsAntibodiesAttentionBioinformaticsBiologicalBiological AssayBiological MarkersCaliberCell Culture SystemCell membraneCellsCellular AssayCharacteristicsChargeChemicalsChemistryConditioned Culture MediaCoupledDataDatabasesDevelopmentDoseEnzyme-Linked Immunosorbent AssayExtracellular ProteinFutureGenesGoalsHistopathologyIn VitroLung Lavage FluidMass Spectrum AnalysisMeasuresMessenger RNAMicellesMicroarray AnalysisModelingModificationMusNatureOutcomeParticle SizePathway AnalysisPathway interactionsPersonal SatisfactionPlayPredictive ValueProceduresPropertyProtein IsoformsProteinsProteomicsProxyPublic HealthQuantitative Structure-Activity RelationshipRangeResearchResearch PersonnelRoentgen RaysRoleScreening procedureSeriesSiliconSilicon DioxideSiteSpectrum AnalysisStatistical ModelsSurfaceSurface PropertiesSystemTestingTissuesTranslatingWorkabsorptionbasebiomaterial compatibilityconsumer productdesigndosimetryexpectationfunctional grouphuman studyin vitro Assayin vivomacrophagenanomaterialsnanoparticlenanoscalenanotoxicologyparticleprogramsprototyperesponsesilanolsize
项目摘要
DESCRIPTION (provided by applicant)
We propose a quantitative structure activity relationship (QSAR) approach to investigate the specific physical and chemical surface properties that influence nanoparticle biocompatibility. Amorphous silica is chosen as an experimental particle due to its widespread use in consumer products, and because it is readily synthesized in a wide range of defined sizes and surface chemistries. Our recent work shows that the bioactivity of amorphous silica is greatly enhanced in particles <50 nm. We hypothesize that this is due to changes in the silanol site surface chemistry as particle diameter is decreased.
Our approach involves three aims: 1) A panel of nanoparticle-induced secreted proteins will be identified using advanced mass spectrometry-based proteomic analysis of conditioned medium from macrophages exposed to amorphous silica, coupled with our existing gene microarray data. Bioinformatic pathway analysis will be performed to select ~20 pathway biomarkers, which will be used to modify an antibody sandwich-based protein ELISA microarray platform for multiplexed response analyses. 2) A series of silicabased particles where size and surface chemistry is selectively altered with functional groups will be prepared and characterized for size, charge, aggregation state, dissolution products and silanol types. X-ray absorption near-edge spectroscopy will be used to identify surface silicon isoforms in particles adsorbed to micelles mimicking cell membranes. The biological responses of each particle will be assessed in multiwell cellular assays with macrophages, using the ELISA microarray platform to provide quantitative measures of dose-response for ~20 different pathway markers. QSAR analyses will be performed with the measured physicochemical parameters and biological response data to identify relationships that correlate most strongly. 3) Particles selected from QSAR analysis will be further tested in mice exposed by intratracheal instillation, and biological responses will be determined by histopathology along with ELISA microarray analysis of bronchial lavage fluid. Comparison of QSAR results obtained in aims 2 and 3 will determine how predictive the in vitro assay is, as well as highlight particle characteristics that are most important for dictating biocompatibility in vivo. The results will determine properties of nano-scale amorphous silica that determine its biocompatibility, and reveal general principals relevant to other types of nanomaterial. In addition, the approach and biomarkers developed from this work will provide a screening platform that can be deployed to a variety of nanomaterials in the future.
描述(由申请人提供)
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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Brian D. Thrall其他文献
356 - A General Proteomics Approach for Site-Specific Quantification of Cysteine Redox Modifications and Its Application for Profiling S-Glutathionylation in Macrophages
- DOI:
10.1016/j.freeradbiomed.2013.10.782 - 发表时间:
2013-11-01 - 期刊:
- 影响因子:
- 作者:
Dian Su;Matthew J Gaffrey;Jia Guo;Therese R.W. Clauss;Brian D. Thrall;Richard d Smith;Wei-Jun Qian - 通讯作者:
Wei-Jun Qian
Brian D. Thrall的其他文献
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{{ truncateString('Brian D. Thrall', 18)}}的其他基金
Key Events in Modulation of Lung Infection Susceptibility by Nanomaterials
纳米材料调节肺部感染易感性的关键事件
- 批准号:
9770860 - 财政年份:2016
- 资助金额:
$ 47.13万 - 项目类别:
Integrating Structive Activity, Biokinetics and Response for ENP Risk Assessment
整合结构活动、生物动力学和反应进行 ENP 风险评估
- 批准号:
8464706 - 财政年份:2010
- 资助金额:
$ 47.13万 - 项目类别:
Integrating Structive Activity, Biokinetics and Response for ENP Risk Assessment
整合结构活动、生物动力学和反应进行 ENP 风险评估
- 批准号:
8675237 - 财政年份:2010
- 资助金额:
$ 47.13万 - 项目类别:
PROTEOMIC ANALYSIS OF THE HMEC MITOGENIC RESPONSE
HMEC 有丝分裂反应的蛋白质组学分析
- 批准号:
7721391 - 财政年份:2008
- 资助金额:
$ 47.13万 - 项目类别:
Sytems Analysis of Nanoparticle Biocompatibility
纳米粒子生物相容性的系统分析
- 批准号:
7497144 - 财政年份:2007
- 资助金额:
$ 47.13万 - 项目类别:
Sytems Analysis of Nanoparticle Biocompatibility
纳米粒子生物相容性的系统分析
- 批准号:
8070832 - 财政年份:2007
- 资助金额:
$ 47.13万 - 项目类别:
Sytems Analysis of Nanoparticle Biocompatibility
纳米粒子生物相容性的系统分析
- 批准号:
8324443 - 财政年份:2007
- 资助金额:
$ 47.13万 - 项目类别:
Sytems Analysis of Nanoparticle Biocompatibility
纳米粒子生物相容性的系统分析
- 批准号:
7673833 - 财政年份:2007
- 资助金额:
$ 47.13万 - 项目类别:
PROTEOMIC ANALYSIS OF THE HMEC MITOGENIC RESPONSE
HMEC 有丝分裂反应的蛋白质组学分析
- 批准号:
7602867 - 财政年份:2007
- 资助金额:
$ 47.13万 - 项目类别:
PROTEOMIC ANALYSIS OF THE HMEC MITOGENIC RESPONSE
HMEC 有丝分裂反应的蛋白质组学分析
- 批准号:
7359107 - 财政年份:2006
- 资助金额:
$ 47.13万 - 项目类别:
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