Journal article
Docetaxel-Loaded PLGA Nanoparticles Improve Efficacy in Taxane-Resistant Triple-Negative Breast Cancer
Nano letters, Vol.17(1), pp.242-248
01/11/2017
DOI: 10.1021/acs.nanolett.6b03971
PMCID: PMC5404392
PMID: 27966988
Abstract
Novel treatment strategies, including nanomedicine, are needed for improving management of triple-negative breast cancer. Patients with triple-negative breast cancer, when considered as a group, have a worse outcome after chemotherapy than patients with breast cancers of other subtypes, a finding that reflects the intrinsically adverse prognosis associated with the disease. The aim of this study was to improve the efficacy of docetaxel by incorporation into a novel nanoparticle platform for the treatment of taxane-resistant triple-negative breast cancer. Rod-shaped nanoparticles encapsulating docetaxel were fabricated using an imprint lithography based technique referred to as Particle Replication in Nonwetting Templates (PRINT). These rod-shaped PLGA-docetaxel nanoparticles were tested in the C3(1)-T-antigen (C3Tag) genetically engineered mouse model (GEMM) of breast cancer that represents the basal-like subtype of triple-negative breast cancer and is resistant to therapeutics from the taxane family. This GEMM recapitulates the genetics of the human disease and is reflective of patient outcome and, therefore, better represents the clinical impact of new therapeutics. Pharmacokinetic analysis showed that delivery of these PLGA-docetaxel nanoparticles increased docetaxel circulation time and provided similar docetaxel exposure to tumor compared to the clinical formulation of docetaxel, Taxotere. These PLGA-docetaxel nanoparticles improved tumor growth inhibition and significantly increased median survival time. This study demonstrates the potential of nanotechnology to improve the therapeutic index of chemotherapies and rescue therapeutic efficacy to treat nonresponsive cancers.
Details
- Title: Subtitle
- Docetaxel-Loaded PLGA Nanoparticles Improve Efficacy in Taxane-Resistant Triple-Negative Breast Cancer
- Creators
- Charles J Bowerman - University of North Carolina at Chapel HillJames D Byrne - University of North Carolina at Chapel HillKevin S Chu - University of North Carolina at Chapel HillAllison N Schorzman - University of North Carolina at Chapel HillAmanda W Keeler - University of North Carolina at Chapel HillCandice A Sherwood - University of North Carolina at Chapel HillJillian L Perry - University of North Carolina at Chapel HillJames C Luft - University of North Carolina at Chapel HillDavid B Darr - University of North Carolina at Chapel HillAllison M Deal - University of North Carolina at Chapel HillMary E Napier - University of North Carolina at Chapel HillWilliam C Zamboni - University of North Carolina at Chapel HillNorman E Sharpless - University of North Carolina at Chapel HillCharles M Perou - University of North Carolina at Chapel HillJoseph M DeSimone - University of North Carolina at Chapel Hill
- Resource Type
- Journal article
- Publication Details
- Nano letters, Vol.17(1), pp.242-248
- DOI
- 10.1021/acs.nanolett.6b03971
- PMID
- 27966988
- PMCID
- PMC5404392
- NLM abbreviation
- Nano Lett
- ISSN
- 1530-6984
- eISSN
- 1530-6992
- Grant note
- R01 CA163896 / NCI NIH HHS U54 CA119343 / NCI NIH HHS U54 CA151652 / NCI NIH HHS P30 CA016086 / NCI NIH HHS P50 CA058223 / NCI NIH HHS
- Language
- English
- Date published
- 01/11/2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiation Oncology
- Record Identifier
- 9984274755502771
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