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Aurora kinase inhib...
Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutic index in vivo
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- Ashton, Susan (author)
- AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.
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- Song, Young Ho (author)
- BIND Therapeut, 325 Vassar St, Cambridge, MA 02139 USA.
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- Nolan, Jim (author)
- BIND Therapeut, 325 Vassar St, Cambridge, MA 02139 USA.
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- Cadogan, Elaine (author)
- AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.
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- Murray, Jim (author)
- AstraZeneca, Pharmaceut Dev, Macclesfield SK10 2NX, Cheshire, England.
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- Odedra, Rajesh (author)
- AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.
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- Foster, John (author)
- AstraZeneca R&D, Drug Safety & Metab, Innovat Med, Alderley Pk, Macclesfield SK10 4TG, Cheshire, England.
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- Hall, Peter A. (author)
- AstraZeneca R&D, Drug Safety & Metab, Innovat Med, Alderley Pk, Macclesfield SK10 4TG, Cheshire, England.
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- Low, Susan (author)
- BIND Therapeut, 325 Vassar St, Cambridge, MA 02139 USA.
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- Taylor, Paula (author)
- AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.
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- Ellston, Rebecca (author)
- AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.
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- Polanska, Urszula M. (author)
- AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.
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- Wilson, Joanne (author)
- AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.
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- Howes, Colin (author)
- AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.
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- Smith, Aaron (author)
- AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.
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- Goodwin, Richard J. A. (author)
- AstraZeneca R&D, Drug Safety & Metab, Innovat Med, Alderley Pk, Macclesfield SK10 4TG, Cheshire, England.
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- Swales, John G. (author)
- AstraZeneca R&D, Drug Safety & Metab, Innovat Med, Alderley Pk, Macclesfield SK10 4TG, Cheshire, England.
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- Strittmatter, Nicole (author)
- Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London SW7 2AZ, England.
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- Takats, Zoltan (author)
- Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London SW7 2AZ, England.
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- Nilsson, Anna (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Andrén, Per (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Trueman, Dawn (author)
- AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.
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- Walker, Mike (author)
- AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.
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- Reimer, Corinne L. (author)
- AstraZeneca, Oncol iMED, Gatehouse Pk, Boston, MA 02451 USA.
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- Troiano, Greg (author)
- BIND Therapeut, 325 Vassar St, Cambridge, MA 02139 USA.
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- Parsons, Donald (author)
- BIND Therapeut, 325 Vassar St, Cambridge, MA 02139 USA.
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- De Witt, David (author)
- BIND Therapeut, 325 Vassar St, Cambridge, MA 02139 USA.
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- Ashford, Marianne (author)
- AstraZeneca, Pharmaceut Dev, Macclesfield SK10 2NX, Cheshire, England.
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- Hrkach, Jeff (author)
- BIND Therapeut, 325 Vassar St, Cambridge, MA 02139 USA.
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- Zale, Stephen (author)
- BIND Therapeut, 325 Vassar St, Cambridge, MA 02139 USA.
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- Jewsbury, Philip J. (author)
- AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.
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- Barry, Simon T. (author)
- AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.
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AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England BIND Therapeut, 325 Vassar St, Cambridge, MA 02139 USA. (creator_code:org_t)
- American Association for the Advancement of Science (AAAS), 2016
- 2016
- English.
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In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 8:325
- Related links:
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http://hdl.handle.ne...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Efforts to apply nanotechnology in cancer have focused almost exclusively on the delivery of cytotoxic drugs to improve therapeutic index. There has been little consideration of molecularly targeted agents, in particular kinase inhibitors, which can also present considerable therapeutic index limitations. We describe the development of Accurin polymeric nanoparticles that encapsulate the clinical candidate AZD2811, an Aurora B kinase inhibitor, using an ion pairing approach. Accurins increase biodistribution to tumor sites and provide extended release of encapsulated drug payloads. AZD2811 nanoparticles containing pharmaceutically acceptable organic acids as ion pairing agents displayed continuous drug release for more than 1 week in vitro and a corresponding extended pharmacodynamic reduction of tumor phosphorylated histone H3 levels in vivo for up to 96 hours after a single administration. A specific AZD2811 nanoparticle formulation profile showed accumulation and retention in tumors with minimal impact on bone marrow pathology, and resulted in lower toxicity and increased efficacy in multiple tumor models at half the dose intensity of AZD1152, a water-soluble prodrug of AZD2811. These studies demonstrate that AZD2811 can be formulated in nanoparticles using ion pairing agents to give improved efficacy and tolerability in preclinical models with less frequent dosing. Accurins specifically, and nanotechnology in general, can increase the therapeutic index of molecularly targeted agents, including kinase inhibitors targeting cell cycle and oncogenic signal transduction pathways, which have to date proved toxic in humans.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Ashton, Susan
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Song, Young Ho
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Nolan, Jim
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Cadogan, Elaine
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Murray, Jim
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Odedra, Rajesh
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show more...
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Foster, John
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Hall, Peter A.
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Low, Susan
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Taylor, Paula
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Ellston, Rebecca
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Polanska, Urszul ...
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Wilson, Joanne
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Howes, Colin
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Smith, Aaron
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Goodwin, Richard ...
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Swales, John G.
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Strittmatter, Ni ...
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Takats, Zoltan
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Nilsson, Anna
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Andrén, Per
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Trueman, Dawn
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Walker, Mike
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Reimer, Corinne ...
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Troiano, Greg
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Parsons, Donald
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De Witt, David
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Ashford, Mariann ...
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Hrkach, Jeff
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Zale, Stephen
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Jewsbury, Philip ...
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Barry, Simon T.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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Science Translat ...
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Uppsala University