Triple-hit therapeutic approach for triple negative breast cancers using docetaxel nanoparticles, EN1-iPeps and RGD

Anabel Sorolla1, Edina Wang1, Tristan D Clemons2

  • 1Cancer Epigenetics, Harry Perkins Institute of Medical Research Nedlands, WA 6009, Australia; School of Human Sciences, The University of Western Australia Crawley, WA 6009, Australia.

Insights

This study introduces novel nanoparticles targeting chemotherapy-resistant triple-negative breast cancer (TNBC). The targeted delivery system effectively reduces tumor growth and induces apoptosis with minimal toxicity, offering a promising new therapeutic strategy.

Area of Science:

  • Oncology
  • Nanotechnology
  • Molecular Biology

Background:

  • Triple-negative breast cancer (TNBC) is aggressive and often develops resistance to chemotherapy, including docetaxel.
  • Overexpression of transcription factor ENGRAILED1 (EN1) is linked to docetaxel resistance in TNBC.

Purpose of the Study:

  • To develop and evaluate a targeted nanoformulation for docetaxel delivery to chemoresistant TNBC.
  • To investigate the efficacy of inhibiting EN1 using interference peptides (EN1-iPeps) conjugated to nanoparticles.

Main Methods:

  • Development of docetaxel-loaded nanoparticles functionalized with EN1-inhibiting peptides (EN1-iPeps) and RGD sequences for enhanced tumor targeting.
  • Assessment of EN1-RGD-iPeps' effect on TNBC cell viability and apoptosis in vitro.
  • Evaluation of nanoparticle internalization via integrins and tumor accumulation after intravenous injection.
  • In vitro and in vivo assessment of the nanoformulation's efficacy in reducing TNBC growth and toxicity.

Main Results:

  • EN1-RGD-iPeps reduced TNBC cell viability and induced apoptosis with minimal impact on normal cells.
  • Nanoparticle uptake in breast cancer cells was mediated by integrins, and intravenous administration increased tumor accumulation.
  • The docetaxel-loaded nanoparticles functionalized with EN1-RGD-iPeps significantly inhibited TNBC growth in vitro and in vivo.
  • The nanoformulation demonstrated no significant toxicity.

Conclusions:

  • Targeted inhibition of EN1 using RGD-functionalized nanoparticles offers a novel therapeutic strategy for chemoresistant TNBC.
  • This nanoformulation shows potential as a safe and effective treatment for TNBC by overcoming chemotherapy resistance.

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