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Antibody/siRNA Nanocarriers Against Wnt Signaling Suppress Oncogenic and Stem-Like Behavior in Triple-Negative Breast

Elise C Hoover1, Emily S Day1,2,3

  • 1Department of Biomedical Engineering, University of Delaware, Newark, Delaware, USA.

Journal of Biomedical Materials Research. Part A
|January 6, 2025
PubMed

Insights

New nanoparticles targeting the Wnt pathway in triple-negative breast cancer (TNBC) effectively suppressed cancer growth. This Wnt-targeted therapy reduced proliferation and drug resistance, offering a promising treatment strategy for TNBC.

Area of Science:

  • Oncology
  • Nanotechnology
  • Molecular Biology

Background:

  • Triple-negative breast cancer (TNBC) presents an aggressive phenotype with limited therapeutic options due to the absence of targeted receptors.
  • The Wnt signaling pathway is frequently activated in TNBC, driving cancer progression and contributing to poor patient prognosis.

Purpose of the Study:

  • To develop and evaluate novel polymer nanoparticles (NPs) designed to inhibit the Wnt signaling pathway specifically in TNBC cells.
  • To investigate the efficacy of these Wnt-targeted NPs in reducing oncogenic and stem-like properties of TNBC cells.

Main Methods:

  • Development of polymer nanoparticles (NPs) functionalized with anti-Frizzled7 (FZD7) antibodies and β-catenin small interfering RNAs (siRNAs).
  • Assessment of the impact of Wnt-targeted NPs on Wnt oncogene suppression and downstream effects in TNBC cells compared to control NPs.

Main Results:

  • Wnt-targeted NPs demonstrated superior suppression of Wnt oncogenes compared to control NPs.
  • Treatment with Wnt-targeted NPs significantly inhibited key oncogenic and stem-like phenotypes, including cell proliferation, drug resistance, and spheroid formation.

Conclusions:

  • Targeting the Wnt signaling pathway via FZD7 and β-catenin offers a promising therapeutic strategy for triple-negative breast cancer.
  • The developed Wnt-targeted nanoparticles effectively counteract the aggressive cellular behaviors driving TNBC progression, suggesting potential for improved patient outcomes.
Keywords:
Frizzled7RNA interferenceantibodiesnanomedicineoncologytargeted therapyβ‐catenin

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