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Docetaxel-Loaded PLGA Nanoparticles Improve Efficacy in Taxane-Resistant Triple-Negative Breast Cancer.
- Source :
-
Nano letters [Nano Lett] 2017 Jan 11; Vol. 17 (1), pp. 242-248. Date of Electronic Publication: 2016 Dec 22. - Publication Year :
- 2017
-
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.
- Subjects :
- A549 Cells
Animals
Antineoplastic Agents pharmacokinetics
Bridged-Ring Compounds metabolism
Cell Survival
Docetaxel
Drug Carriers chemistry
Drug Liberation
Drug Resistance, Neoplasm
Female
Humans
Mice, Nude
Particle Size
Polylactic Acid-Polyglycolic Acid Copolymer
Surface Properties
Taxoids chemistry
Taxoids metabolism
Taxoids pharmacokinetics
Triple Negative Breast Neoplasms genetics
Antineoplastic Agents administration & dosage
Antineoplastic Agents chemistry
Lactic Acid chemistry
Nanoparticles chemistry
Polyglycolic Acid chemistry
Taxoids administration & dosage
Triple Negative Breast Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1530-6992
- Volume :
- 17
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nano letters
- Publication Type :
- Academic Journal
- Accession number :
- 27966988
- Full Text :
- https://doi.org/10.1021/acs.nanolett.6b03971