Systemic RALA/iNOS nanoparticles: a potent gene therapy for metastatic breast cancer coupled as a biomarker of treatment

Show simple item record

dc.contributor.author McCrudden, Cian M.
dc.contributor.author McBride, John W.
dc.contributor.author McCaffrey, Joanne
dc.contributor.author Ali, Ahlam A.
dc.contributor.author Dunne, Nicholas J.
dc.contributor.author Kett, Vicky L.
dc.contributor.author Coulter, Jonathan A.
dc.contributor.author Robson, Tracy
dc.contributor.author McCarthy, Helen O.
dc.date.accessioned 2017-09-26T11:39:18Z
dc.date.available 2017-09-26T11:39:18Z
dc.date.issued 2017
dc.identifier.citation McCrudden, C. M., McBride, J. W., McCaffrey, J., Ali, A. A., Dunne, N. J., Kett, V. L., Coulter, J. A., Robson, T. and McCarthy, H. O. (2017) 'Systemic RALA/iNOS nanoparticles: a potent gene therapy for metastatic breast cancer coupled as a biomarker of treatment', Molecular Therapy - Nucleic Acids, 6, (10pp). doi: 10.1016/j.omtn.2016.12.010 en
dc.identifier.volume 6
dc.identifier.startpage 249
dc.identifier.endpage 258
dc.identifier.issn 2162-2531
dc.identifier.uri http://hdl.handle.net/10468/4780
dc.identifier.doi 10.1016/j.omtn.2016.12.010
dc.description.abstract This study aimed to determine the therapeutic benefit of a nanoparticular formulation for the delivery of inducible nitric oxide synthase (iNOS) gene therapy in a model of breast cancer metastasis. Nanoparticles comprising a cationic peptide vector, RALA, and plasmid DNA were formulated and characterized using a range of physiochemical analyses. Nanoparticles complexed using iNOS plasmids and RALA approximated 60 nm in diameter with a charge of 25 mV. A vector neutralization assay, performed to determine the immunogenicity of nanoparticles in immunocompetent C57BL/6 mice, revealed that no vector neutralization was evident. Nanoparticles harboring iNOS plasmids (constitutively active cytomegalovirus [ CMV]driven or transcriptionally regulated human osteocalcin [ hOC]-driven) evoked iNOS protein expression and nitrite accumulation and impaired clonogenicity in the highly aggressive MDA-MB-231 human breast cancer model. Micrometastases of MDA-MB-231-luc-D3H1 cells were established in female BALB/c SCID mice by intracardiac delivery. Nanoparticulate RALA/CMV-iNOS or RALA/hOC-iNOS increased median survival in mice bearing micrometastases by 27% compared with controls and also provoked elevated blood nitrite levels. Additionally, iNOS gene therapy sensitized MDA-MB-231-lucD3H1 tumors to docetaxel treatment. Studies demonstrated that systemically delivered RALA-iNOS nanoparticles have therapeutic potential for the treatment of metastatic breast cancer. Furthermore, detection of nitrite levels in the blood serves as a reliable biomarker of treatment. en
dc.description.sponsorship Cancer Research UK (C17372/A14271, C17372/A18475) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Cell Press en
dc.relation.uri http://www.sciencedirect.com/science/article/pii/S216225311630378X?via%3Dihub
dc.rights © 2017, the Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) en
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject Nitric oxide synthase en
dc.subject Prostate cancer en
dc.subject Tumor cells en
dc.subject Mesenchymal transition en
dc.subject Amphipathic peptide en
dc.subject Human osteocalcin en
dc.subject Carcinoma en
dc.subject Radiation en
dc.subject Promoter en
dc.subject Delivery en
dc.title Systemic RALA/iNOS nanoparticles: a potent gene therapy for metastatic breast cancer coupled as a biomarker of treatment en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Joanne McCaffrey, Phamacology and Therapeutics, University College Cork, Cork, Ireland. +353-21-490-3000 Email: joanne.mccaffrey@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.internal.wokid WOS:000397092100022
dc.contributor.funder Cancer Research UK
dc.description.status Peer reviewed en
dc.identifier.journaltitle Molecular Therapy - Nucleic Acids en
dc.internal.IRISemailaddress joanne.mccaffrey@ucc.ie en


Files in this item

This item appears in the following Collection(s)

Show simple item record

© 2017, the Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) Except where otherwise noted, this item's license is described as © 2017, the Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
This website uses cookies. By using this website, you consent to the use of cookies in accordance with the UCC Privacy and Cookies Statement. For more information about cookies and how you can disable them, visit our Privacy and Cookies statement