Docetaxel-loaded PLGA nanoparticles improve efficacy in taxane-resistant triple-negative breast cancer

Charles J. Bowerman, James D. Byrne, Kevin S. Chu, Allison N. Schorzman, Amanda W. Keeler, Candice A. Sherwood, Jillian L. Perry, James C. Luft, David B. Darr, Allison M. Deal, Mary E. Napier, William C. Zamboni, Norman E. Sharpless, Charles M. Perou, Joseph M. DeSimone

Research output: Research - peer-reviewArticle

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.

LanguageEnglish (US)
Pages242-248
Number of pages7
JournalNano Letters
Volume17
Issue number1
DOIs
StatePublished - 2017

Fingerprint

breast
cancer
nanoparticles
docetaxel
Nanoparticles
taxane
polylactic acid-polyglycolic acid copolymer
Chemotherapy
Tumors
chemotherapy
mice
rods
tumors
Medical nanotechnology
Pharmacokinetics
Antigens
Nanotechnology
Lithography
Genetics
encapsulating

Keywords

  • Chemoresistance
  • Docetaxel
  • Genetically engineered mouse model
  • Nanoparticles
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanical Engineering

Cite this

Bowerman, C. J., Byrne, J. D., Chu, K. S., Schorzman, A. N., Keeler, A. W., Sherwood, C. A., ... DeSimone, J. M. (2017). Docetaxel-loaded PLGA nanoparticles improve efficacy in taxane-resistant triple-negative breast cancer. Nano Letters, 17(1), 242-248. DOI: 10.1021/acs.nanolett.6b03971

Docetaxel-loaded PLGA nanoparticles improve efficacy in taxane-resistant triple-negative breast cancer. / Bowerman, Charles J.; Byrne, James D.; Chu, Kevin S.; Schorzman, Allison N.; Keeler, Amanda W.; Sherwood, Candice A.; Perry, Jillian L.; Luft, James C.; Darr, David B.; Deal, Allison M.; Napier, Mary E.; Zamboni, William C.; Sharpless, Norman E.; Perou, Charles M.; DeSimone, Joseph M.

In: Nano Letters, Vol. 17, No. 1, 2017, p. 242-248.

Research output: Research - peer-reviewArticle

Bowerman, CJ, Byrne, JD, Chu, KS, Schorzman, AN, Keeler, AW, Sherwood, CA, Perry, JL, Luft, JC, Darr, DB, Deal, AM, Napier, ME, Zamboni, WC, Sharpless, NE, Perou, CM & DeSimone, JM 2017, 'Docetaxel-loaded PLGA nanoparticles improve efficacy in taxane-resistant triple-negative breast cancer' Nano Letters, vol 17, no. 1, pp. 242-248. DOI: 10.1021/acs.nanolett.6b03971
Bowerman CJ, Byrne JD, Chu KS, Schorzman AN, Keeler AW, Sherwood CA et al. Docetaxel-loaded PLGA nanoparticles improve efficacy in taxane-resistant triple-negative breast cancer. Nano Letters. 2017;17(1):242-248. Available from, DOI: 10.1021/acs.nanolett.6b03971
Bowerman, Charles J. ; Byrne, James D. ; Chu, Kevin S. ; Schorzman, Allison N. ; Keeler, Amanda W. ; Sherwood, Candice A. ; Perry, Jillian L. ; Luft, James C. ; Darr, David B. ; Deal, Allison M. ; Napier, Mary E. ; Zamboni, William C. ; Sharpless, Norman E. ; Perou, Charles M. ; DeSimone, Joseph M./ Docetaxel-loaded PLGA nanoparticles improve efficacy in taxane-resistant triple-negative breast cancer. In: Nano Letters. 2017 ; Vol. 17, No. 1. pp. 242-248
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