Functionalized carbon nanotubes in the brain: cellular internalization and neuroinflammatory responses
The potential use of functionalized carbon nanotubes (f-CNTs) for drug and gene delivery to the central nervous system (CNS) and as neural substrates makes the understanding of their in vivo interactions with the neural tissue essential. The aim of this study was to investigate the interactions betw...
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| Veröffentlicht in: | PloS one 2013-11, Vol.8 (11), p.e80964 |
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| description | The potential use of functionalized carbon nanotubes (f-CNTs) for drug and gene delivery to the central nervous system (CNS) and as neural substrates makes the understanding of their in vivo interactions with the neural tissue essential. The aim of this study was to investigate the interactions between chemically functionalized multi-walled carbon nanotubes (f-MWNTs) and the neural tissue following cortical stereotactic administration. Two different f-MWNT constructs were used in these studies: shortened (by oxidation) amino-functionalized MWNT (oxMWNT-NH3(+)) and amino-functionalized MWNT (MWNT-NH3(+)). Parenchymal distribution of the stereotactically injected f-MWNTs was assessed by histological examination. Both f-MWNT were uptaken by different types of neural tissue cells (microglia, astrocytes and neurons), however different patterns of cellular internalization were observed between the nanotubes. Furthermore, immunohistochemical staining for specific markers of glial cell activation (GFAP and CD11b) was performed and secretion of inflammatory cytokines was investigated using real-time PCR (qRT-PCR). Injections of both f-MWNT constructs led to a local and transient induction of inflammatory cytokines at early time points. Oxidation of nanotubes seemed to induce significant levels of GFAP and CD11b over-expression in areas peripheral to the f-MWNT injection site. These results highlight the importance of nanotube functionalization on their interaction with brain tissue that is deemed critical for the development nanotube-based vector systems for CNS applications. |
| doi_str_mv | 10.1371/journal.pone.0080964 |
| format | Article |
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The aim of this study was to investigate the interactions between chemically functionalized multi-walled carbon nanotubes (f-MWNTs) and the neural tissue following cortical stereotactic administration. Two different f-MWNT constructs were used in these studies: shortened (by oxidation) amino-functionalized MWNT (oxMWNT-NH3(+)) and amino-functionalized MWNT (MWNT-NH3(+)). Parenchymal distribution of the stereotactically injected f-MWNTs was assessed by histological examination. Both f-MWNT were uptaken by different types of neural tissue cells (microglia, astrocytes and neurons), however different patterns of cellular internalization were observed between the nanotubes. Furthermore, immunohistochemical staining for specific markers of glial cell activation (GFAP and CD11b) was performed and secretion of inflammatory cytokines was investigated using real-time PCR (qRT-PCR). Injections of both f-MWNT constructs led to a local and transient induction of inflammatory cytokines at early time points. Oxidation of nanotubes seemed to induce significant levels of GFAP and CD11b over-expression in areas peripheral to the f-MWNT injection site. These results highlight the importance of nanotube functionalization on their interaction with brain tissue that is deemed critical for the development nanotube-based vector systems for CNS applications.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0080964</identifier><identifier>PMID: 24260521</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Ammonia ; Animals ; Astrocytes ; Astrocytes - drug effects ; Astrocytes - metabolism ; Astrocytes - pathology ; Biological Transport ; Biomarkers - metabolism ; Brain ; Brain - drug effects ; Brain - metabolism ; Brain - pathology ; Carbon ; CD11b antigen ; CD11b Antigen - genetics ; CD11b Antigen - metabolism ; Cell activation ; Central nervous system ; Chemical Sciences ; Cortex ; Cytokines ; Cytokines - genetics ; Cytokines - metabolism ; Disease ; Drug delivery systems ; Female ; Gene Expression ; Gene transfer ; Glial cells ; Glial Fibrillary Acidic Protein ; Immunohistochemistry ; In vivo methods and tests ; Inflammation ; Inflammation - chemically induced ; Inflammation - metabolism ; Inflammation - pathology ; Injections, Intraventricular ; Internalization ; Laboratories ; Localization ; Medical imaging ; Medicinal Chemistry ; Mice ; Mice, Inbred C57BL ; Microglia ; Microglia - drug effects ; Microglia - metabolism ; Microglia - pathology ; Multi wall carbon nanotubes ; Nanotechnology ; Nanotubes ; Nanotubes, Carbon - chemistry ; Nanotubes, Carbon - toxicity ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Neurons - drug effects ; Neurons - metabolism ; Neurons - pathology ; Neurophysiology ; Neurosciences ; Overexpression ; Oxidation ; Oxidation-Reduction ; Pharmacy ; Physiology ; Stereotaxic Techniques ; Studies ; Substrates</subject><ispartof>PloS one, 2013-11, Vol.8 (11), p.e80964</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Bardi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/3.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>2013 Bardi et al 2013 Bardi et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c726t-1decd4520cecc1ab4f3857e1b8e096039ab458b5eca9ca866c1c405f2d8b60973</citedby><cites>FETCH-LOGICAL-c726t-1decd4520cecc1ab4f3857e1b8e096039ab458b5eca9ca866c1c405f2d8b60973</cites><orcidid>0000-0002-1090-296X ; 0000-0002-0630-510X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832421/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832421/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24260521$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-02558894$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Bardi, Giuseppe</creatorcontrib><creatorcontrib>Nunes, Antonio</creatorcontrib><creatorcontrib>Gherardini, Lisa</creatorcontrib><creatorcontrib>Bates, Katie</creatorcontrib><creatorcontrib>Al-Jamal, Khuloud T</creatorcontrib><creatorcontrib>Gaillard, Claire</creatorcontrib><creatorcontrib>Prato, Maurizio</creatorcontrib><creatorcontrib>Bianco, Alberto</creatorcontrib><creatorcontrib>Pizzorusso, Tommaso</creatorcontrib><creatorcontrib>Kostarelos, Kostas</creatorcontrib><title>Functionalized carbon nanotubes in the brain: cellular internalization and neuroinflammatory responses</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The potential use of functionalized carbon nanotubes (f-CNTs) for drug and gene delivery to the central nervous system (CNS) and as neural substrates makes the understanding of their in vivo interactions with the neural tissue essential. The aim of this study was to investigate the interactions between chemically functionalized multi-walled carbon nanotubes (f-MWNTs) and the neural tissue following cortical stereotactic administration. Two different f-MWNT constructs were used in these studies: shortened (by oxidation) amino-functionalized MWNT (oxMWNT-NH3(+)) and amino-functionalized MWNT (MWNT-NH3(+)). Parenchymal distribution of the stereotactically injected f-MWNTs was assessed by histological examination. Both f-MWNT were uptaken by different types of neural tissue cells (microglia, astrocytes and neurons), however different patterns of cellular internalization were observed between the nanotubes. Furthermore, immunohistochemical staining for specific markers of glial cell activation (GFAP and CD11b) was performed and secretion of inflammatory cytokines was investigated using real-time PCR (qRT-PCR). Injections of both f-MWNT constructs led to a local and transient induction of inflammatory cytokines at early time points. Oxidation of nanotubes seemed to induce significant levels of GFAP and CD11b over-expression in areas peripheral to the f-MWNT injection site. These results highlight the importance of nanotube functionalization on their interaction with brain tissue that is deemed critical for the development nanotube-based vector systems for CNS applications.</description><subject>Ammonia</subject><subject>Animals</subject><subject>Astrocytes</subject><subject>Astrocytes - drug effects</subject><subject>Astrocytes - metabolism</subject><subject>Astrocytes - pathology</subject><subject>Biological Transport</subject><subject>Biomarkers - metabolism</subject><subject>Brain</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Brain - pathology</subject><subject>Carbon</subject><subject>CD11b antigen</subject><subject>CD11b Antigen - genetics</subject><subject>CD11b Antigen - metabolism</subject><subject>Cell activation</subject><subject>Central nervous system</subject><subject>Chemical Sciences</subject><subject>Cortex</subject><subject>Cytokines</subject><subject>Cytokines - genetics</subject><subject>Cytokines - metabolism</subject><subject>Disease</subject><subject>Drug delivery systems</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Gene transfer</subject><subject>Glial cells</subject><subject>Glial Fibrillary Acidic Protein</subject><subject>Immunohistochemistry</subject><subject>In vivo methods and tests</subject><subject>Inflammation</subject><subject>Inflammation - chemically induced</subject><subject>Inflammation - metabolism</subject><subject>Inflammation - pathology</subject><subject>Injections, Intraventricular</subject><subject>Internalization</subject><subject>Laboratories</subject><subject>Localization</subject><subject>Medical imaging</subject><subject>Medicinal Chemistry</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microglia</subject><subject>Microglia - drug effects</subject><subject>Microglia - metabolism</subject><subject>Microglia - pathology</subject><subject>Multi wall carbon nanotubes</subject><subject>Nanotechnology</subject><subject>Nanotubes</subject><subject>Nanotubes, Carbon - chemistry</subject><subject>Nanotubes, Carbon - toxicity</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Neurons - pathology</subject><subject>Neurophysiology</subject><subject>Neurosciences</subject><subject>Overexpression</subject><subject>Oxidation</subject><subject>Oxidation-Reduction</subject><subject>Pharmacy</subject><subject>Physiology</subject><subject>Stereotaxic Techniques</subject><subject>Studies</subject><subject>Substrates</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk22L1DAQx4so3rn6DUQLgnAvdk2a9CG-EJbD8xYWDnx6G6bpdDdLNzmT9PD89Ka3vWMrCtIXLdPf_z-ZmUySvKRkQVlJ3-1s7wx0i2trcEFIRUTBHyWnVLBsXmSEPT76Pkmeeb8jJGdVUTxNTjKeFSTP6GnSXvRGBW2jk_6FTarA1dakBowNfY0-1SYNW0xrB9q8TxV2Xd-Bi-GA7k4EgzoF06QGe2e1aTvY7yFYd5s69PF4Hv3z5EkLnccX43uWfLv4-PX8cr6--rQ6X67nqsyKMKcNqobnGVGoFIWat6zKS6R1hbE8wkQM5VWdowKhINaiqOIkb7OmqgsiSjZLXh98rzvr5dgiLynPBSd8aMAsWR2IxsJOXju9B3crLWh5F7BuI8EFrTqULSMCEeIZQHElhFAUWQ5UqVLUNTTR68OYra_32Cg0wUE3MZ3-MXorN_ZGsorFEdBocHYw2P4hu1yu5RAjWZ5XleA3A_tmTObsjx59-Ed5I7WBWEEcho2J1V57JZe8rDIquBCRWvyFik-De63ihWp1jE8EZxNBZAL-DBvovZerL5__n736PmXfHrFbhC5sve364U75KcgPoHLWe4ftQ7sokcM-3HdDDvsgx32IslfHE3oQ3S8A-w2XAQgz</recordid><startdate>20131118</startdate><enddate>20131118</enddate><creator>Bardi, Giuseppe</creator><creator>Nunes, Antonio</creator><creator>Gherardini, Lisa</creator><creator>Bates, Katie</creator><creator>Al-Jamal, Khuloud T</creator><creator>Gaillard, Claire</creator><creator>Prato, Maurizio</creator><creator>Bianco, Alberto</creator><creator>Pizzorusso, Tommaso</creator><creator>Kostarelos, Kostas</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-1090-296X</orcidid><orcidid>https://orcid.org/0000-0002-0630-510X</orcidid></search><sort><creationdate>20131118</creationdate><title>Functionalized carbon nanotubes in the brain: cellular internalization and neuroinflammatory responses</title><author>Bardi, Giuseppe ; Nunes, Antonio ; Gherardini, Lisa ; Bates, Katie ; Al-Jamal, Khuloud T ; Gaillard, Claire ; Prato, Maurizio ; Bianco, Alberto ; Pizzorusso, Tommaso ; Kostarelos, Kostas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c726t-1decd4520cecc1ab4f3857e1b8e096039ab458b5eca9ca866c1c405f2d8b60973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Ammonia</topic><topic>Animals</topic><topic>Astrocytes</topic><topic>Astrocytes - 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bardi, Giuseppe</au><au>Nunes, Antonio</au><au>Gherardini, Lisa</au><au>Bates, Katie</au><au>Al-Jamal, Khuloud T</au><au>Gaillard, Claire</au><au>Prato, Maurizio</au><au>Bianco, Alberto</au><au>Pizzorusso, Tommaso</au><au>Kostarelos, Kostas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functionalized carbon nanotubes in the brain: cellular internalization and neuroinflammatory responses</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-11-18</date><risdate>2013</risdate><volume>8</volume><issue>11</issue><spage>e80964</spage><pages>e80964-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The potential use of functionalized carbon nanotubes (f-CNTs) for drug and gene delivery to the central nervous system (CNS) and as neural substrates makes the understanding of their in vivo interactions with the neural tissue essential. The aim of this study was to investigate the interactions between chemically functionalized multi-walled carbon nanotubes (f-MWNTs) and the neural tissue following cortical stereotactic administration. Two different f-MWNT constructs were used in these studies: shortened (by oxidation) amino-functionalized MWNT (oxMWNT-NH3(+)) and amino-functionalized MWNT (MWNT-NH3(+)). Parenchymal distribution of the stereotactically injected f-MWNTs was assessed by histological examination. Both f-MWNT were uptaken by different types of neural tissue cells (microglia, astrocytes and neurons), however different patterns of cellular internalization were observed between the nanotubes. Furthermore, immunohistochemical staining for specific markers of glial cell activation (GFAP and CD11b) was performed and secretion of inflammatory cytokines was investigated using real-time PCR (qRT-PCR). Injections of both f-MWNT constructs led to a local and transient induction of inflammatory cytokines at early time points. Oxidation of nanotubes seemed to induce significant levels of GFAP and CD11b over-expression in areas peripheral to the f-MWNT injection site. These results highlight the importance of nanotube functionalization on their interaction with brain tissue that is deemed critical for the development nanotube-based vector systems for CNS applications.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24260521</pmid><doi>10.1371/journal.pone.0080964</doi><tpages>e80964</tpages><orcidid>https://orcid.org/0000-0002-1090-296X</orcidid><orcidid>https://orcid.org/0000-0002-0630-510X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-11, Vol.8 (11), p.e80964 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1459404005 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Ammonia Animals Astrocytes Astrocytes - drug effects Astrocytes - metabolism Astrocytes - pathology Biological Transport Biomarkers - metabolism Brain Brain - drug effects Brain - metabolism Brain - pathology Carbon CD11b antigen CD11b Antigen - genetics CD11b Antigen - metabolism Cell activation Central nervous system Chemical Sciences Cortex Cytokines Cytokines - genetics Cytokines - metabolism Disease Drug delivery systems Female Gene Expression Gene transfer Glial cells Glial Fibrillary Acidic Protein Immunohistochemistry In vivo methods and tests Inflammation Inflammation - chemically induced Inflammation - metabolism Inflammation - pathology Injections, Intraventricular Internalization Laboratories Localization Medical imaging Medicinal Chemistry Mice Mice, Inbred C57BL Microglia Microglia - drug effects Microglia - metabolism Microglia - pathology Multi wall carbon nanotubes Nanotechnology Nanotubes Nanotubes, Carbon - chemistry Nanotubes, Carbon - toxicity Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Neurons - drug effects Neurons - metabolism Neurons - pathology Neurophysiology Neurosciences Overexpression Oxidation Oxidation-Reduction Pharmacy Physiology Stereotaxic Techniques Studies Substrates |
| title | Functionalized carbon nanotubes in the brain: cellular internalization and neuroinflammatory responses |
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