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ONTOLOGY SOURCE REFERENCE
Term Source NameMONPONPOCHEBI
Term Source File
Term Source Versionv1.xv1.xv1.x
Term Source DescriptionMGED OntologyNanoparticle OntologyNanoparticle OntologyChebi Entity of Biological Interest
INVESTIGATION
Investigation IdentifierNCL200612A
Investigation TitleDendrimer-Based MRI Contrast Agents
Investigation DescriptionThe objective of the Dendritic Nanotechnologies, Inc. - NCL collaboration is to characterize a PAMAM dendrimer with an associated gadolinium chelate MRI contrast agent. The nanomaterials submitted for testing at the NCL were (NCL20) G4 tris (hydroxyl) terminated PAMAM dendrimer, (NCL21) G4 pyrrolidinone terminated PAMAM dendrimer, (NCL22) G4.5 COONa terminated PAMAM dendrimer, (NCL23) G4.5 COONa terminated PAMAM dendrimer-MagnevistÆ complex, (NCL25) G4 tris (hydroxyl) terminated PAMAM dendrimer-MagnevistÆ complex, and (NCL26) G4 pyrrolidinone terminated PAMAM dendrimer-MagnevistÆ complex. Commercially available MagnevistÆ (NCL24) was used as a control. NCL studies addressed in this report can be divided into three main categories: physicochemical characterization; immunotoxicology; in vitro toxicology.
Investigation Submission DateDec-06
Investigation Public Release DateDec-06
INVESTIGATION PUBLICATIONS
Investigation PubMed ID18095846
Investigation Publication DOI10.2217/17435889.2.6.789
Investigation Publication Author listHall JB, Dobrovolskaia MA, Patri AK, McNeil SE
Investigation Publication TitleCharacterization of nanoparticles for therapeutics
Investigation Publication Statuspeer reviewed
Investigation Publication Status Term Accession Number
Investigation Publication Status Term Source REFNPO
INVESTIGATION CONTACTS
Investigation Person Last NameMcNeilPatriPatriDobrovolskaia
Investigation Person First NameScottAnilAnilMarina
Investigation Person Mid Initials
Investigation Person Emailmcneils@mail.nih.govpatria@mail.nih.govpatria@mail.nih.govmarina@mail.nih.gov
Investigation Person Phone3018466939301846523730184652373018466352
Investigation Person Fax
Investigation Person AddressMSC 1050 Boyles Street, Frederick, MD 21702MSC 1050 Boyles Street, Frederick, MD 21702MSC 1050 Boyles Street, Frederick, MD 21702MSC 1050 Boyles Street, Frederick, MD 21702
Investigation Person AffiliationNanotechnology Characterization LaboratoryNanotechnology Characterization LaboratoryNanotechnology Characterization LaboratoryNanotechnology Characterization Laboratory
Investigation Person Rolesinvestigatorinvestigatorinvestigatorinvestigator
Investigation Person Roles Term Accession Number
Investigation Person Roles Term Source REFMOMOMOMO
STUDY
Study Identifier
Study TitlePhysical Chemical Characterization
Study Submission DateDec-06
Study Public Release DateDec-06
Study DescriptionDynamic light scattering (DLS) technique was used to measure the hydrodynamic size of this dendritic nanomaterial. The effects of sample concentration, buffer, and temperature on the hydrodynamic size (stability) also were measured. Purity was analyzed by HPLC and Capillary Electrophoresis. MALDI-TOF Mass spectrometry was used to obtain the molecular weight information and to determine the purity, existence of dimers, trimers, and trailing generations in the sample. Gadolinium quantitation, which is important to determine the relaxivity as a MRI contrast agent, was carried out by Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). Fractionation methods such as Size Exclusion Chromatography (SEC) and Asymmetric-flow Field Flow Fractionation (AFFF) were used to determine the molecular weight information as well as purity. Finally, a 3T clinical MRI machine was used to obtain relaxivity measurements on this sample to compare with free MagnevistÆ. No significant relaxivity change was observed upon association of MagnevistÆ with the dendrimer.
Study File Names_Sample-Material.txt
STUDY DESIGN DESCRIPTORS
Study Design Typecomparison
Study Design Type Term Accession Number
Study Design Type Term Source REF
STUDY PUBLICATIONS
Study PubMed ID
Study Publication DOI
Study Publication Author list
Study Publication Title
Study Publication Status
Study Publication Status Term Accession Number
Study Publication Status Term Source REF
STUDY FACTORS
Study Factor Namemedia solventconcentration
Study Factor Typeconditioncondition
Study Factor Type Term Accession Number
Study Factor Type Term Source REFNPO
STUDY ASSAYS
Study Assay Measurement Type% hemolysis; is hemolytic
Study Assay Measurement Type Term Accession Number
Study Assay Measurement Type Term Source REFNPO
Study Assay Technology Type
Study Assay Technology Type Term Accession Number
Study Assay Technology Type Term Source REFNPO
Study Assay Technology Platform
Study Assay File Name
STUDY PROTOCOLS
Study Protocol NameAnalysis of Nanoparticle Hemolytic Properties
Study Protocol Typesize
Study Protocol Type Term Accession Number
Study Protocol Type Term Source REFNPO
Study Protocol DescriptionAnalysis of Nanoparticle Hemolytic Properties
Study Protocol URI
Study Protocol Version1.00
Study Protocol Parameters Name
Study Protocol Parameters Name Term Accession Number
Study Protocol Parameters Name Term Source REF
Study Protocol Components Name
Study Protocol Components Type
Study Protocol Components Type Term Accession Number
Study Protocol Components Type Term Source REF
STUDY CONTACTS
Study Person Last Namepatri
Study Person First Nameanil
Study Person Mid Initial
Study Person Emailpatria@mail.nih.gov
Study Person Phone3018465237
Study Person Fax
Study Person AddressMSC 1050 Boyles Street, Frederick, MD 21702
Study Person AffiliationNanotechnology Characterization Laboratory
Study Person Rolesinvestigator
Study Person Roles Term Accession Number
Study Person Roles Term Source REFMO
STUDY
Study Identifier
Study TitleCytotoxicity Characterization
Study Submission DateDec-06
Study Public Release DateDec-06
Study DescriptionEvaluation of nanoparticle blood contact properties included study of the effects on coagulation pathways and the integrity of blood cellular components. NCL22, NCL23 and NCL24 were free of hemolytic and platelet aggregation effects, though a mild increase in collagen-induced platelet aggregation was noted at high NCL23 and NCL24 concentrations.Important findings included potential interference of NCL22, NCL23 and NCL24 with plasma coagulation factors, and complement activation by NCL23 and NCL24. Particle effects on in vitro immune function were also evaluated. NCL22, NCL23 and NCL24 were not internalized via phagocytic uptake, and did not alter leukocyte proliferation, macrophage oxidative burst or macrophage chemotaxis. None of the test materials were capable of inducing cytokines in human peripheral blood mononuclear cells, and minimal effects on natural killer cell activity were observed. Of potential clinical relevance, NCL23
Study File Names_Sample-Material.txt
STUDY DESIGN DESCRIPTORS
Study Design Typecomparison
Study Design Type Term Accession Number
Study Design Type Term Source REF
STUDY PUBLICATIONS
Study PubMed ID
Study Publication DOI
Study Publication Author list
Study Publication Title
Study Publication Status
Study Publication Status Term Accession Number
Study Publication Status Term Source REF
STUDY FACTORS
Study Factor Nametimeconcentrationconcentration
Study Factor Typeconditionconditioncondition
Study Factor Type Term Accession Number
Study Factor Type Term Source REF
STUDY ASSAYS
Study Assay Measurement Typecell viability
Study Assay Measurement Type Term Accession Number
Study Assay Measurement Type Term Source REFNPO
Study Assay Technology Type
Study Assay Technology Type Term Accession Number
Study Assay Technology Type Term Source REF
Study Assay Technology Platform
Study Assay File Namea_MTT-Cytoxicity.txt
STUDY PROTOCOLS
Study Protocol NameLLC-PK1 Kidney Cytotoxicity Assay
Study Protocol Typecytotoxicity
Study Protocol Type Term Accession Number
Study Protocol Type Term Source REFNPO
Study Protocol Description MTT Cytotoxicity Assay in LLC-PK1 Cells
Study Protocol URI
Study Protocol Version1.0
Study Protocol Parameters Namecell type
Study Protocol Parameters Name Term Accession Number
Study Protocol Parameters Name Term Source REF
Study Protocol Components Name
Study Protocol Components Type
Study Protocol Components Type Term Accession Number
Study Protocol Components Type Term Source REFNPO
STUDY CONTACTS
Study Person Last NameDobrovolskaia
Study Person First NameMarina
Study Person Mid Initial
Study Person Emailmarina@mail.nih.gov
Study Person Phone3018466352
Study Person Fax
Study Person AddressMSC 1050 Boyles Street, Frederick, MD 21702
Study Person AffiliationNanotechnology Characterization Laboratory
Study Person Rolesinvestigator
Study Person Roles Term Accession Number
Study Person Roles Term Source REFMO
STUDY
Study Identifier
Study TitleIn Vitro Immunotoxicology Characterization
Study Submission Date
Study Public Release Date
Study DescriptionToxicologyNanoparticle biocompatibility was evaluated in porcine renal proximal tubule and human hepatocarcinoma cell lines. NCL22, NCL23 and NCL24 were found to be minimally cytotoxic to these cells lines, under the experimental conditions utilized. Further in vitro mechanistic toxicology studies were not warranted at this time.In summary, in vitro evaluation of the dendrimer-MagnevistÆ complex demonstrated a high degree of biocompatibility, with minimal negative effects on cell viability, immune function and blood components. Future studies will examine the in vivo tumor imaging capabilities of the contrast agents in animal models.
Study File Name
STUDY DESIGN DESCRIPTORS
Study Design Typecomparison
Study Design Type Term Accession Number
Study Design Type Term Source REF
STUDY PUBLICATIONS
Study PubMed ID
Study Publication DOI
Study Publication Author list
Study Publication Title
Study Publication Status
Study Publication Status Term Accession Number
Study Publication Status Term Source REF
STUDY FACTORS
Study Factor Nameconcentration
Study Factor Typecondition
Study Factor Type Term Accession Number
Study Factor Type Term Source REFNPO
STUDY ASSAYS
Study Assay Measurement Type# of CFU-GM colonies
Study Assay Measurement Type Term Accession Number
Study Assay Measurement Type Term Source REFNPO
Study Assay Technology Type
Study Assay Technology Type Term Accession Number
Study Assay Technology Type Term Source REF
Study Assay Technology Platform
Study Assay File Namea_CFU_GM.txt
STUDY PROTOCOL
Study Protocol NameMouse Granulocyte-Macrophage Colony-Forming Unit Assay
Study Protocol Typeimmune cell function
Study Protocol Type Term Accession Number
Study Protocol Type Term Source REF
Study Protocol DescriptionQuantitative analysis of granulocyte-macrophage colony forming units
Study Protocol URI
Study Protocol Version1.0
Study Protocol Parameters Name
Study Protocol Parameters Name Term Accession Number
Study Protocol Parameters Name Term Source REF
Study Protocol Components Name
Study Protocol Components Type
Study Protocol Components Type Term Accession Number
Study Protocol Components Type Term Source REF
STUDY CONTACTS
Study Person Last NameDobrovolskaia
Study Person First NameMarina
Study Person Mid Initial
Study Person Emailmarina@mail.nih.gov
Study Person Phone3018466352
Study Person Fax
Study Person AddressMSC 1050 Boyles Street, Frederick, MD 21702
Study Person AffiliationNanotechnology Characterization Laboratory
Study Person Rolesinvestigator
Study Person Roles Term Accession Number
Study Person Roles Term Source REFMO