Treatment of Invasive Brain Tumors Using a Chain-like Nanoparticle
Glioblastoma multiforme is generally recalcitrant to current surgical and local radiotherapeutic approaches. Moreover, systemic chemotherapeutic approaches are impeded by the blood-tumor barrier. To circumvent limitations in the latter area, we developed a multicomponent, chain-like nanoparticle tha...
Uloženo v:
| Vydáno v: | Cancer research (Chicago, Ill.) Ročník 75; číslo 7; s. 1356 |
|---|---|
| Hlavní autoři: | , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
United States
01.04.2015
|
| Témata: | |
| ISSN: | 1538-7445, 1538-7445 |
| On-line přístup: | Zjistit podrobnosti o přístupu |
| Tagy: |
Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
|
| Abstract | Glioblastoma multiforme is generally recalcitrant to current surgical and local radiotherapeutic approaches. Moreover, systemic chemotherapeutic approaches are impeded by the blood-tumor barrier. To circumvent limitations in the latter area, we developed a multicomponent, chain-like nanoparticle that can penetrate brain tumors, composed of three iron oxide nanospheres and one drug-loaded liposome linked chemically into a linear chain-like assembly. Unlike traditional small-molecule drugs or spherical nanotherapeutics, this oblong-shaped, flexible nanochain particle possessed a unique ability to gain access to and accumulate at glioma sites. Vascular targeting of nanochains to the αvβ3 integrin receptor resulted in a 18.6-fold greater drug dose administered to brain tumors than standard chemotherapy. By 2 hours after injection, when nanochains had exited the blood stream and docked at vascular beds in the brain, the application of an external low-power radiofrequency field was sufficient to remotely trigger rapid drug release. This effect was produced by mechanically induced defects in the liposomal membrane caused by the oscillation of the iron oxide portion of the nanochain. In vivo efficacy studies conducted in two different mouse orthotopic models of glioblastoma illustrated how enhanced targeting by the nanochain facilitates widespread site-specific drug delivery. Our findings offer preclinical proof-of-concept for a broadly improved method for glioblastoma treatment. |
|---|---|
| AbstractList | Glioblastoma multiforme is generally recalcitrant to current surgical and local radiotherapeutic approaches. Moreover, systemic chemotherapeutic approaches are impeded by the blood-tumor barrier. To circumvent limitations in the latter area, we developed a multicomponent, chain-like nanoparticle that can penetrate brain tumors, composed of three iron oxide nanospheres and one drug-loaded liposome linked chemically into a linear chain-like assembly. Unlike traditional small-molecule drugs or spherical nanotherapeutics, this oblong-shaped, flexible nanochain particle possessed a unique ability to gain access to and accumulate at glioma sites. Vascular targeting of nanochains to the αvβ3 integrin receptor resulted in a 18.6-fold greater drug dose administered to brain tumors than standard chemotherapy. By 2 hours after injection, when nanochains had exited the blood stream and docked at vascular beds in the brain, the application of an external low-power radiofrequency field was sufficient to remotely trigger rapid drug release. This effect was produced by mechanically induced defects in the liposomal membrane caused by the oscillation of the iron oxide portion of the nanochain. In vivo efficacy studies conducted in two different mouse orthotopic models of glioblastoma illustrated how enhanced targeting by the nanochain facilitates widespread site-specific drug delivery. Our findings offer preclinical proof-of-concept for a broadly improved method for glioblastoma treatment. Glioblastoma multiforme is generally recalcitrant to current surgical and local radiotherapeutic approaches. Moreover, systemic chemotherapeutic approaches are impeded by the blood-tumor barrier. To circumvent limitations in the latter area, we developed a multicomponent, chain-like nanoparticle that can penetrate brain tumors, composed of three iron oxide nanospheres and one drug-loaded liposome linked chemically into a linear chain-like assembly. Unlike traditional small-molecule drugs or spherical nanotherapeutics, this oblong-shaped, flexible nanochain particle possessed a unique ability to gain access to and accumulate at glioma sites. Vascular targeting of nanochains to the αvβ3 integrin receptor resulted in a 18.6-fold greater drug dose administered to brain tumors than standard chemotherapy. By 2 hours after injection, when nanochains had exited the blood stream and docked at vascular beds in the brain, the application of an external low-power radiofrequency field was sufficient to remotely trigger rapid drug release. This effect was produced by mechanically induced defects in the liposomal membrane caused by the oscillation of the iron oxide portion of the nanochain. In vivo efficacy studies conducted in two different mouse orthotopic models of glioblastoma illustrated how enhanced targeting by the nanochain facilitates widespread site-specific drug delivery. Our findings offer preclinical proof-of-concept for a broadly improved method for glioblastoma treatment.Glioblastoma multiforme is generally recalcitrant to current surgical and local radiotherapeutic approaches. Moreover, systemic chemotherapeutic approaches are impeded by the blood-tumor barrier. To circumvent limitations in the latter area, we developed a multicomponent, chain-like nanoparticle that can penetrate brain tumors, composed of three iron oxide nanospheres and one drug-loaded liposome linked chemically into a linear chain-like assembly. Unlike traditional small-molecule drugs or spherical nanotherapeutics, this oblong-shaped, flexible nanochain particle possessed a unique ability to gain access to and accumulate at glioma sites. Vascular targeting of nanochains to the αvβ3 integrin receptor resulted in a 18.6-fold greater drug dose administered to brain tumors than standard chemotherapy. By 2 hours after injection, when nanochains had exited the blood stream and docked at vascular beds in the brain, the application of an external low-power radiofrequency field was sufficient to remotely trigger rapid drug release. This effect was produced by mechanically induced defects in the liposomal membrane caused by the oscillation of the iron oxide portion of the nanochain. In vivo efficacy studies conducted in two different mouse orthotopic models of glioblastoma illustrated how enhanced targeting by the nanochain facilitates widespread site-specific drug delivery. Our findings offer preclinical proof-of-concept for a broadly improved method for glioblastoma treatment. |
| Author | Doolittle, Elizabeth Abramowski, Aaron Bauer, Lisa Gopalakrishnan, Ramamurthy Karathanasis, Efstathios Ghaghada, Ketan B Basilion, James P Mcginnity, James Shah, Shruti Brady-Kalnay, Susann M Griswold, Mark A Peiris, Pubudu M Toy, Randall Hoimes, Christopher |
| Author_xml | – sequence: 1 givenname: Pubudu M surname: Peiris fullname: Peiris, Pubudu M organization: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio. Department of Radiology, Case Western Reserve University, Cleveland, Ohio. Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio – sequence: 2 givenname: Aaron surname: Abramowski fullname: Abramowski, Aaron organization: Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio. Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio – sequence: 3 givenname: James surname: Mcginnity fullname: Mcginnity, James organization: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio. Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio – sequence: 4 givenname: Elizabeth surname: Doolittle fullname: Doolittle, Elizabeth organization: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio. Department of Radiology, Case Western Reserve University, Cleveland, Ohio. Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio – sequence: 5 givenname: Randall surname: Toy fullname: Toy, Randall organization: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio. Department of Radiology, Case Western Reserve University, Cleveland, Ohio. Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio – sequence: 6 givenname: Ramamurthy surname: Gopalakrishnan fullname: Gopalakrishnan, Ramamurthy organization: Department of Radiology, Case Western Reserve University, Cleveland, Ohio. Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio – sequence: 7 givenname: Shruti surname: Shah fullname: Shah, Shruti organization: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio. Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio – sequence: 8 givenname: Lisa surname: Bauer fullname: Bauer, Lisa organization: Department of Radiology, Case Western Reserve University, Cleveland, Ohio. Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio. Department of Physics, Case Western Reserve University, Cleveland, Ohio – sequence: 9 givenname: Ketan B surname: Ghaghada fullname: Ghaghada, Ketan B organization: Edward B. Singleton Department of Pediatric Radiology, Texas Children's Hospital, Houston, Texas. Department of Radiology, Baylor College of Medicine, Houston, Texas – sequence: 10 givenname: Christopher surname: Hoimes fullname: Hoimes, Christopher organization: University Hospitals Case Medical Center, Cleveland, Ohio. Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio – sequence: 11 givenname: Susann M surname: Brady-Kalnay fullname: Brady-Kalnay, Susann M organization: Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio. Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio – sequence: 12 givenname: James P surname: Basilion fullname: Basilion, James P organization: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio. Department of Radiology, Case Western Reserve University, Cleveland, Ohio. Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio. Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio – sequence: 13 givenname: Mark A surname: Griswold fullname: Griswold, Mark A organization: Department of Radiology, Case Western Reserve University, Cleveland, Ohio. Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio. Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio – sequence: 14 givenname: Efstathios surname: Karathanasis fullname: Karathanasis, Efstathios email: stathis@case.edu organization: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio. Department of Radiology, Case Western Reserve University, Cleveland, Ohio. Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio. Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio. stathis@case.edu |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25627979$$D View this record in MEDLINE/PubMed |
| BookMark | eNpNT1tLwzAYDTJxF_0JSh59yUzSfrk8bmXqYMyX7bmkaarRNp1NO_DfO3GCT-dwbnCmaBTa4BC6ZXTOGKgHSqkikEo-zxZbwlLCIKUXaMIgUUSmKYz-8TGaxvh-qgCjcIXGHASXWuoJWu46Z_rGhR63FV6Ho4n-6PCyMz7g3dC0XcT76MMrNjh7O4mk9h8Ob01oD6brva3dNbqsTB3dzRlnaP-42mXPZPPytM4WG2JTKXvCtEwYFAUYVQoJztqKVoLaJDEnpwReWVExm_BCCCtLKAUI0MYpa6RQWvMZuv_dPXTt5-Binzc-WlfXJrh2iDkTQqtESP4TvTtHh6JxZX7ofGO6r_zvN_8GQONb9w |
| CitedBy_id | crossref_primary_10_3390_molecules24030409 crossref_primary_10_1002_adfm_201600642 crossref_primary_10_1002_wnan_1387 crossref_primary_10_1016_j_addr_2016_09_006 crossref_primary_10_1016_j_biomaterials_2021_121359 crossref_primary_10_1039_C7NR02370G crossref_primary_10_1016_j_ejpb_2019_10_004 crossref_primary_10_1155_2018_4341580 crossref_primary_10_1007_s13346_020_00880_8 crossref_primary_10_1016_j_bmc_2020_115823 crossref_primary_10_1002_smll_201801022 crossref_primary_10_2147_IJN_S247985 crossref_primary_10_1109_JERM_2022_3149685 crossref_primary_10_1080_17435889_2025_2534324 crossref_primary_10_1002_adfm_201601369 crossref_primary_10_1002_wnan_1439 crossref_primary_10_1016_j_nano_2020_102216 crossref_primary_10_1080_17425247_2017_1316262 crossref_primary_10_1016_j_addr_2020_06_010 crossref_primary_10_1016_j_bioactmat_2016_03_003 crossref_primary_10_1371_journal_pone_0220474 crossref_primary_10_1002_smll_201802563 crossref_primary_10_1186_s12987_017_0061_6 crossref_primary_10_1016_j_addr_2015_12_001 crossref_primary_10_3390_ijms231911134 crossref_primary_10_3390_life14010132 crossref_primary_10_3390_nano6010003 crossref_primary_10_1002_adfm_201504185 crossref_primary_10_1371_journal_pone_0204296 crossref_primary_10_3390_pharmaceutics15122658 crossref_primary_10_1016_j_lfs_2021_119326 crossref_primary_10_1021_acsbiomaterials_6b00438 crossref_primary_10_2217_nnm_2020_0066 crossref_primary_10_1016_j_jconrel_2019_01_022 crossref_primary_10_1002_wnan_1571 crossref_primary_10_1016_j_biomaterials_2018_01_044 crossref_primary_10_1016_j_jddst_2024_106322 crossref_primary_10_3390_pharmaceutics13081262 crossref_primary_10_1016_j_nano_2015_12_375 crossref_primary_10_3390_bioengineering5040088 crossref_primary_10_1016_j_jconrel_2015_09_039 crossref_primary_10_1002_adtp_201900118 crossref_primary_10_1016_j_jconrel_2015_09_038 crossref_primary_10_1038_s41467_019_09856_w crossref_primary_10_1021_acsbiomaterials_8b01173 crossref_primary_10_1039_C9NR02876E crossref_primary_10_1002_adhm_202001044 crossref_primary_10_1159_000488145 crossref_primary_10_1007_s11051_016_3719_0 crossref_primary_10_1007_s11481_016_9687_4 |
| ContentType | Journal Article |
| Copyright | 2015 American Association for Cancer Research. |
| Copyright_xml | – notice: 2015 American Association for Cancer Research. |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1158/0008-5472.CAN-14-1540 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1538-7445 |
| ExternalDocumentID | 25627979 |
| Genre | Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NCI NIH HHS grantid: P30CA043703 – fundername: NCI NIH HHS grantid: R25 CA148052 – fundername: NCI NIH HHS grantid: R01 CA177716 – fundername: NCATS NIH HHS grantid: UL1 TR000439 – fundername: NCI NIH HHS grantid: P30 CA043703 – fundername: NCATS NIH HHS grantid: UL1TR000439 – fundername: NCI NIH HHS grantid: K12 CA076917 – fundername: NIBIB NIH HHS grantid: T32 EB007509 – fundername: NCI NIH HHS grantid: R01CA177716 – fundername: NCI NIH HHS grantid: R25CA148052 |
| GroupedDBID | --- -ET 18M 29B 2WC 34G 39C 53G 5GY 5RE 5VS 6J9 AAFWJ AAJMC ABOCM ACGFO ACIWK ACPRK ADBBV ADCOW ADNWM AENEX AETEA AFHIN AFRAH ALMA_UNASSIGNED_HOLDINGS BAWUL BTFSW CGR CS3 CUY CVF DIK DU5 EBS ECM EIF EJD F5P FRP GX1 H13 IH2 KQ8 L7B LSO NPM OK1 P0W P2P PQQKQ RCR RHI RNS SJN TR2 W2D W8F WH7 WOQ YKV YZZ 7X8 |
| ID | FETCH-LOGICAL-c477t-197315bb5a8d675eccf0f60c33a973d52fc6f1c32b66c7d5d65659ae8ca768992 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 63 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000351948900022&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1538-7445 |
| IngestDate | Fri Sep 05 09:06:45 EDT 2025 Mon Aug 18 01:30:34 EDT 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 7 |
| Language | English |
| License | 2015 American Association for Cancer Research. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c477t-197315bb5a8d675eccf0f60c33a973d52fc6f1c32b66c7d5d65659ae8ca768992 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | http://doi.org/10.1158/0008-5472.CAN-14-1540 |
| PMID | 25627979 |
| PQID | 1669836729 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_1669836729 pubmed_primary_25627979 |
| PublicationCentury | 2000 |
| PublicationDate | 2015-04-01 |
| PublicationDateYYYYMMDD | 2015-04-01 |
| PublicationDate_xml | – month: 04 year: 2015 text: 2015-04-01 day: 01 |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Cancer research (Chicago, Ill.) |
| PublicationTitleAlternate | Cancer Res |
| PublicationYear | 2015 |
| SSID | ssj0005105 |
| Score | 2.418817 |
| Snippet | Glioblastoma multiforme is generally recalcitrant to current surgical and local radiotherapeutic approaches. Moreover, systemic chemotherapeutic approaches are... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 1356 |
| SubjectTerms | Animals Antineoplastic Agents - administration & dosage Antineoplastic Agents - chemistry Blood-Brain Barrier Brain Neoplasms - drug therapy Brain Neoplasms - metabolism Brain Neoplasms - pathology Doxorubicin - administration & dosage Drug Carriers - administration & dosage Drug Carriers - chemistry Ferric Compounds - chemistry Glioblastoma - drug therapy Glioblastoma - metabolism Glioblastoma - pathology Integrin alphaVbeta3 - metabolism Mice, Nude Nanoparticles - chemistry Neoplasm Invasiveness Xenograft Model Antitumor Assays |
| Title | Treatment of Invasive Brain Tumors Using a Chain-like Nanoparticle |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/25627979 https://www.proquest.com/docview/1669836729 |
| Volume | 75 |
| WOSCitedRecordID | wos000351948900022&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LSwMxEA5qRbz4ftQXEbxGu9k8T6JFUbClhyq9lSSbYFF3a2v9_U52t_QkCF72sMsuYXYy-WbmSz6ELnhIqBfcEqmpJUw5TVTmGYGVijJhjWmVdciXJ9ntqsFA9-qC27SmVc5jYhmos8LFGvlVIoRWqQAseD3-JFE1KnZXawmNZdRIAcpESpccLE4L5xWFsZzUkjFe7-BJuIobGBThTNLL9k2XJDC4sv7xG8osV5v7zf-Ocwtt1DgT31SOsY2WfL6D1jp1J30X3fbnDHNcBPyYf5vIY8e3UTEC92cfxWSKSzoBNrj9CjfJ--jNYwjGkGVXH91Dz_d3_fYDqfUUiGNSfpEkylRxa7lRGeQJ8PNCK4iWS1MDTzJOgxMhcSm1QjiZ8QywHtfGK2cgKdGa7qOVvMj9IcICYqjgaQA8EhhAXqMss0ZQm3rIer1rovO5dYbgr7EJYXJfzKbDhX2a6KAy8XBcHawxBPhFpZb66A9vH6N1wC68ItGcoEaA2epP0ar7_hpNJ2elI8C12-v8AAU1upw |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Treatment+of+Invasive+Brain+Tumors+Using+a+Chain-like+Nanoparticle&rft.jtitle=Cancer+research+%28Chicago%2C+Ill.%29&rft.au=Peiris%2C+Pubudu+M&rft.au=Abramowski%2C+Aaron&rft.au=Mcginnity%2C+James&rft.au=Doolittle%2C+Elizabeth&rft.date=2015-04-01&rft.issn=1538-7445&rft.eissn=1538-7445&rft.volume=75&rft.issue=7&rft.spage=1356&rft_id=info:doi/10.1158%2F0008-5472.CAN-14-1540&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1538-7445&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1538-7445&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1538-7445&client=summon |