IN VITRO CHARACTERIZATION OF A TARGETED, DYE-LOADED NANODEVICE FOR INTRAOPERATIVE TUMOR DELINEATION
Abstract OBJECTIVE To synthesize and complete in vitro characterization of a novel, tumor-targeted nanodevice for visible intraoperative delineation of brain tumors. METHODS The ability of dye-loaded polyacrylamide nanoparticles (NP) containing methylene blue, Coomassie blue, or indocyanine green to...
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| Veröffentlicht in: | Neurosurgery 2009-05, Vol.64 (5), p.965-972 |
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| creator | Orringer, Daniel A. Koo, Yong-Eun L. Chen, Thomas Kim, Gwangseong Hah, Hoe Jin Xu, Hao Wang, Shouyan Keep, Richard Philbert, Martin A. Kopelman, Raoul Sagher, Oren |
| description | Abstract
OBJECTIVE
To synthesize and complete in vitro characterization of a novel, tumor-targeted nanodevice for visible intraoperative delineation of brain tumors.
METHODS
The ability of dye-loaded polyacrylamide nanoparticles (NP) containing methylene blue, Coomassie blue, or indocyanine green to cause color change in the 9L glioma cell lines was evaluated. Cells were incubated with dye-loaded NPs, photographed, and analyzed colorimetrically. Confocal microscopy was used to determine subcellular localization of NPs in treated cells.
RESULTS
Incubation of glioma cell lines with dye-loaded NPs resulted in clearly visible, quantifiable cell tagging in a dose- and time-dependent manner. Dye-loaded NPs were observed to bind to the surface and become internalized by glioma cells. Coating the NP surface with F3, a peptide that binds to the tumor cell surface receptor nucleolin, significantly increased NP affinity for glioma cells. F3 targeting also significantly increased the rate of cell tagging by dye-loaded NPs. Finally, F3-targeted NPs demonstrated specificity for targeting various cancer cell lines based on their surface expression of cell surface nucleolin.
CONCLUSION
F3-targeted dye-loaded NPs efficiently cause definitive color change in glioma cells. This report represents the first use of targeted NPs to cause a visible color change in tumor cell lines. Similar nanodevices may be used in the future to enable visible intraoperative tumor delineation during tumor resection. |
| doi_str_mv | 10.1227/01.NEU.0000344150.81021.AA |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2701445</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1227/01.NEU.0000344150.81021.AA</oup_id><sourcerecordid>1985699742</sourcerecordid><originalsourceid>FETCH-LOGICAL-c528t-40f5a1a81ba87f015038e73c1215dd3cfe7d220bb990076bc793db61f5f9c98f3</originalsourceid><addsrcrecordid>eNqVkUGP0zAUhC0EYsvCX0AWiBsNfo4dxxyQrMTdjVQSFKUVcLEcJ4auuk1JWiT-PWZb7cIRXyzZ38wbexB6BSQCSsU7AlGpVxEJK2YMOIlSIBQipR6hGXDK5oww8hjNCLB0Hsvk8wV6Nk03hEDCRPoUXYAMBPBkhlxR4nXR1BXOrlWtskbXxVfVFFWJqwVWuFH1lW50_hbnX_R8Walc57hUZZXrdZFpvKhqXJRNrapPug66tcbN6mM4zPWyKPWd03P0xNvt1L8475dotdBNdh3sropMLeeO0_QQQntuwabQ2lR4Et4Vp72IHVDgXRc734uOUtK2UhIiktYJGXdtAp576WTq40v04eS7P7a3fef63WG0W7MfN7d2_GUGuzH_3uw238234aehIvwU48Hg9dlgHH4c--lgbobjuAuZDciUJ1IKRgP1_kS5cZimsff3E4CYPwUZAiYUZB4KMncFGaWC-OXfGR-k50YC8OYM2MnZrR_tzm2me44CS2LJZeD4iRuO-_8J8Bvfs6Ch</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1985699742</pqid></control><display><type>article</type><title>IN VITRO CHARACTERIZATION OF A TARGETED, DYE-LOADED NANODEVICE FOR INTRAOPERATIVE TUMOR DELINEATION</title><source>MEDLINE</source><source>Journals@Ovid Complete</source><creator>Orringer, Daniel A. ; Koo, Yong-Eun L. ; Chen, Thomas ; Kim, Gwangseong ; Hah, Hoe Jin ; Xu, Hao ; Wang, Shouyan ; Keep, Richard ; Philbert, Martin A. ; Kopelman, Raoul ; Sagher, Oren</creator><creatorcontrib>Orringer, Daniel A. ; Koo, Yong-Eun L. ; Chen, Thomas ; Kim, Gwangseong ; Hah, Hoe Jin ; Xu, Hao ; Wang, Shouyan ; Keep, Richard ; Philbert, Martin A. ; Kopelman, Raoul ; Sagher, Oren</creatorcontrib><description>Abstract
OBJECTIVE
To synthesize and complete in vitro characterization of a novel, tumor-targeted nanodevice for visible intraoperative delineation of brain tumors.
METHODS
The ability of dye-loaded polyacrylamide nanoparticles (NP) containing methylene blue, Coomassie blue, or indocyanine green to cause color change in the 9L glioma cell lines was evaluated. Cells were incubated with dye-loaded NPs, photographed, and analyzed colorimetrically. Confocal microscopy was used to determine subcellular localization of NPs in treated cells.
RESULTS
Incubation of glioma cell lines with dye-loaded NPs resulted in clearly visible, quantifiable cell tagging in a dose- and time-dependent manner. Dye-loaded NPs were observed to bind to the surface and become internalized by glioma cells. Coating the NP surface with F3, a peptide that binds to the tumor cell surface receptor nucleolin, significantly increased NP affinity for glioma cells. F3 targeting also significantly increased the rate of cell tagging by dye-loaded NPs. Finally, F3-targeted NPs demonstrated specificity for targeting various cancer cell lines based on their surface expression of cell surface nucleolin.
CONCLUSION
F3-targeted dye-loaded NPs efficiently cause definitive color change in glioma cells. This report represents the first use of targeted NPs to cause a visible color change in tumor cell lines. Similar nanodevices may be used in the future to enable visible intraoperative tumor delineation during tumor resection.</description><identifier>ISSN: 0148-396X</identifier><identifier>EISSN: 1524-4040</identifier><identifier>DOI: 10.1227/01.NEU.0000344150.81021.AA</identifier><identifier>PMID: 19404156</identifier><identifier>CODEN: NRSRDY</identifier><language>eng</language><publisher>Hagerstown, MD: Oxford University Press</publisher><subject>Acrylic Resins - administration & dosage ; Acrylic Resins - metabolism ; Biological and medical sciences ; Brain cancer ; Cell Line, Tumor ; Colorimetry - methods ; Dose-Response Relationship, Drug ; Dyes ; Epitopes ; Fluorescent Dyes ; Glioma ; Glioma - metabolism ; Glioma - pathology ; Glioma - ultrastructure ; Humans ; Medical sciences ; Microscopy, Confocal ; Microscopy, Electron, Scanning - methods ; Nanoparticles - administration & dosage ; Neurosurgery ; Nucleolin ; Phosphoproteins - metabolism ; RNA-Binding Proteins - metabolism ; Subcellular Fractions - metabolism ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Time Factors</subject><ispartof>Neurosurgery, 2009-05, Vol.64 (5), p.965-972</ispartof><rights>Copyright © 2009 by the Congress of Neurological Surgeons</rights><rights>2009 INIST-CNRS</rights><rights>Copyright © Congress of Neurological Surgeons</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c528t-40f5a1a81ba87f015038e73c1215dd3cfe7d220bb990076bc793db61f5f9c98f3</citedby><cites>FETCH-LOGICAL-c528t-40f5a1a81ba87f015038e73c1215dd3cfe7d220bb990076bc793db61f5f9c98f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21463959$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19404156$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Orringer, Daniel A.</creatorcontrib><creatorcontrib>Koo, Yong-Eun L.</creatorcontrib><creatorcontrib>Chen, Thomas</creatorcontrib><creatorcontrib>Kim, Gwangseong</creatorcontrib><creatorcontrib>Hah, Hoe Jin</creatorcontrib><creatorcontrib>Xu, Hao</creatorcontrib><creatorcontrib>Wang, Shouyan</creatorcontrib><creatorcontrib>Keep, Richard</creatorcontrib><creatorcontrib>Philbert, Martin A.</creatorcontrib><creatorcontrib>Kopelman, Raoul</creatorcontrib><creatorcontrib>Sagher, Oren</creatorcontrib><title>IN VITRO CHARACTERIZATION OF A TARGETED, DYE-LOADED NANODEVICE FOR INTRAOPERATIVE TUMOR DELINEATION</title><title>Neurosurgery</title><addtitle>Neurosurgery</addtitle><description>Abstract
OBJECTIVE
To synthesize and complete in vitro characterization of a novel, tumor-targeted nanodevice for visible intraoperative delineation of brain tumors.
METHODS
The ability of dye-loaded polyacrylamide nanoparticles (NP) containing methylene blue, Coomassie blue, or indocyanine green to cause color change in the 9L glioma cell lines was evaluated. Cells were incubated with dye-loaded NPs, photographed, and analyzed colorimetrically. Confocal microscopy was used to determine subcellular localization of NPs in treated cells.
RESULTS
Incubation of glioma cell lines with dye-loaded NPs resulted in clearly visible, quantifiable cell tagging in a dose- and time-dependent manner. Dye-loaded NPs were observed to bind to the surface and become internalized by glioma cells. Coating the NP surface with F3, a peptide that binds to the tumor cell surface receptor nucleolin, significantly increased NP affinity for glioma cells. F3 targeting also significantly increased the rate of cell tagging by dye-loaded NPs. Finally, F3-targeted NPs demonstrated specificity for targeting various cancer cell lines based on their surface expression of cell surface nucleolin.
CONCLUSION
F3-targeted dye-loaded NPs efficiently cause definitive color change in glioma cells. This report represents the first use of targeted NPs to cause a visible color change in tumor cell lines. Similar nanodevices may be used in the future to enable visible intraoperative tumor delineation during tumor resection.</description><subject>Acrylic Resins - administration & dosage</subject><subject>Acrylic Resins - metabolism</subject><subject>Biological and medical sciences</subject><subject>Brain cancer</subject><subject>Cell Line, Tumor</subject><subject>Colorimetry - methods</subject><subject>Dose-Response Relationship, Drug</subject><subject>Dyes</subject><subject>Epitopes</subject><subject>Fluorescent Dyes</subject><subject>Glioma</subject><subject>Glioma - metabolism</subject><subject>Glioma - pathology</subject><subject>Glioma - ultrastructure</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Microscopy, Confocal</subject><subject>Microscopy, Electron, Scanning - methods</subject><subject>Nanoparticles - administration & dosage</subject><subject>Neurosurgery</subject><subject>Nucleolin</subject><subject>Phosphoproteins - metabolism</subject><subject>RNA-Binding Proteins - metabolism</subject><subject>Subcellular Fractions - metabolism</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Time Factors</subject><issn>0148-396X</issn><issn>1524-4040</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqVkUGP0zAUhC0EYsvCX0AWiBsNfo4dxxyQrMTdjVQSFKUVcLEcJ4auuk1JWiT-PWZb7cIRXyzZ38wbexB6BSQCSsU7AlGpVxEJK2YMOIlSIBQipR6hGXDK5oww8hjNCLB0Hsvk8wV6Nk03hEDCRPoUXYAMBPBkhlxR4nXR1BXOrlWtskbXxVfVFFWJqwVWuFH1lW50_hbnX_R8Walc57hUZZXrdZFpvKhqXJRNrapPug66tcbN6mM4zPWyKPWd03P0xNvt1L8475dotdBNdh3sropMLeeO0_QQQntuwabQ2lR4Et4Vp72IHVDgXRc734uOUtK2UhIiktYJGXdtAp576WTq40v04eS7P7a3fef63WG0W7MfN7d2_GUGuzH_3uw238234aehIvwU48Hg9dlgHH4c--lgbobjuAuZDciUJ1IKRgP1_kS5cZimsff3E4CYPwUZAiYUZB4KMncFGaWC-OXfGR-k50YC8OYM2MnZrR_tzm2me44CS2LJZeD4iRuO-_8J8Bvfs6Ch</recordid><startdate>20090501</startdate><enddate>20090501</enddate><creator>Orringer, Daniel A.</creator><creator>Koo, Yong-Eun L.</creator><creator>Chen, Thomas</creator><creator>Kim, Gwangseong</creator><creator>Hah, Hoe Jin</creator><creator>Xu, Hao</creator><creator>Wang, Shouyan</creator><creator>Keep, Richard</creator><creator>Philbert, Martin A.</creator><creator>Kopelman, Raoul</creator><creator>Sagher, Oren</creator><general>Oxford University Press</general><general>Lippincott Williams & Wilkins</general><general>Wolters Kluwer Health, Inc</general><scope>IQODW</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20090501</creationdate><title>IN VITRO CHARACTERIZATION OF A TARGETED, DYE-LOADED NANODEVICE FOR INTRAOPERATIVE TUMOR DELINEATION</title><author>Orringer, Daniel A. ; Koo, Yong-Eun L. ; Chen, Thomas ; Kim, Gwangseong ; Hah, Hoe Jin ; Xu, Hao ; Wang, Shouyan ; Keep, Richard ; Philbert, Martin A. ; Kopelman, Raoul ; Sagher, Oren</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c528t-40f5a1a81ba87f015038e73c1215dd3cfe7d220bb990076bc793db61f5f9c98f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Acrylic Resins - administration & dosage</topic><topic>Acrylic Resins - metabolism</topic><topic>Biological and medical sciences</topic><topic>Brain cancer</topic><topic>Cell Line, Tumor</topic><topic>Colorimetry - methods</topic><topic>Dose-Response Relationship, Drug</topic><topic>Dyes</topic><topic>Epitopes</topic><topic>Fluorescent Dyes</topic><topic>Glioma</topic><topic>Glioma - metabolism</topic><topic>Glioma - pathology</topic><topic>Glioma - ultrastructure</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Microscopy, Confocal</topic><topic>Microscopy, Electron, Scanning - methods</topic><topic>Nanoparticles - administration & dosage</topic><topic>Neurosurgery</topic><topic>Nucleolin</topic><topic>Phosphoproteins - metabolism</topic><topic>RNA-Binding Proteins - metabolism</topic><topic>Subcellular Fractions - metabolism</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Orringer, Daniel A.</creatorcontrib><creatorcontrib>Koo, Yong-Eun L.</creatorcontrib><creatorcontrib>Chen, Thomas</creatorcontrib><creatorcontrib>Kim, Gwangseong</creatorcontrib><creatorcontrib>Hah, Hoe Jin</creatorcontrib><creatorcontrib>Xu, Hao</creatorcontrib><creatorcontrib>Wang, Shouyan</creatorcontrib><creatorcontrib>Keep, Richard</creatorcontrib><creatorcontrib>Philbert, Martin A.</creatorcontrib><creatorcontrib>Kopelman, Raoul</creatorcontrib><creatorcontrib>Sagher, Oren</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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>PubMed Central (Full Participant titles)</collection><jtitle>Neurosurgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Orringer, Daniel A.</au><au>Koo, Yong-Eun L.</au><au>Chen, Thomas</au><au>Kim, Gwangseong</au><au>Hah, Hoe Jin</au><au>Xu, Hao</au><au>Wang, Shouyan</au><au>Keep, Richard</au><au>Philbert, Martin A.</au><au>Kopelman, Raoul</au><au>Sagher, Oren</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IN VITRO CHARACTERIZATION OF A TARGETED, DYE-LOADED NANODEVICE FOR INTRAOPERATIVE TUMOR DELINEATION</atitle><jtitle>Neurosurgery</jtitle><addtitle>Neurosurgery</addtitle><date>2009-05-01</date><risdate>2009</risdate><volume>64</volume><issue>5</issue><spage>965</spage><epage>972</epage><pages>965-972</pages><issn>0148-396X</issn><eissn>1524-4040</eissn><coden>NRSRDY</coden><abstract>Abstract
OBJECTIVE
To synthesize and complete in vitro characterization of a novel, tumor-targeted nanodevice for visible intraoperative delineation of brain tumors.
METHODS
The ability of dye-loaded polyacrylamide nanoparticles (NP) containing methylene blue, Coomassie blue, or indocyanine green to cause color change in the 9L glioma cell lines was evaluated. Cells were incubated with dye-loaded NPs, photographed, and analyzed colorimetrically. Confocal microscopy was used to determine subcellular localization of NPs in treated cells.
RESULTS
Incubation of glioma cell lines with dye-loaded NPs resulted in clearly visible, quantifiable cell tagging in a dose- and time-dependent manner. Dye-loaded NPs were observed to bind to the surface and become internalized by glioma cells. Coating the NP surface with F3, a peptide that binds to the tumor cell surface receptor nucleolin, significantly increased NP affinity for glioma cells. F3 targeting also significantly increased the rate of cell tagging by dye-loaded NPs. Finally, F3-targeted NPs demonstrated specificity for targeting various cancer cell lines based on their surface expression of cell surface nucleolin.
CONCLUSION
F3-targeted dye-loaded NPs efficiently cause definitive color change in glioma cells. This report represents the first use of targeted NPs to cause a visible color change in tumor cell lines. Similar nanodevices may be used in the future to enable visible intraoperative tumor delineation during tumor resection.</abstract><cop>Hagerstown, MD</cop><pub>Oxford University Press</pub><pmid>19404156</pmid><doi>10.1227/01.NEU.0000344150.81021.AA</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Neurosurgery, 2009-05, Vol.64 (5), p.965-972 |
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| subjects | Acrylic Resins - administration & dosage Acrylic Resins - metabolism Biological and medical sciences Brain cancer Cell Line, Tumor Colorimetry - methods Dose-Response Relationship, Drug Dyes Epitopes Fluorescent Dyes Glioma Glioma - metabolism Glioma - pathology Glioma - ultrastructure Humans Medical sciences Microscopy, Confocal Microscopy, Electron, Scanning - methods Nanoparticles - administration & dosage Neurosurgery Nucleolin Phosphoproteins - metabolism RNA-Binding Proteins - metabolism Subcellular Fractions - metabolism Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Time Factors |
| title | IN VITRO CHARACTERIZATION OF A TARGETED, DYE-LOADED NANODEVICE FOR INTRAOPERATIVE TUMOR DELINEATION |
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