10.57647/jnsc.2025.1506.22

Chitosan Nanoparticle-Mediated Dual Delivery of Quercetin and Paclitaxel Attenuates EMT and Angiogenesis Via ZEB1 and TIMP-3 Regulation in Triple-Negative Breast Cancer

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  • Hamed Dadashi1,
  • Amirreza Nazemiyeh1,
  • Niloufar Ahdeno1,
  • Parniya Kehtari1,
  • Samar Mahari1,
  • Yadollah Omidi2,
  • Somayeh Vandghanooni3,
  • Morteza Eskandani1,
  1. Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
  2. Department of Pharmaceutical Sciences, Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, United States
  3. Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Received: 01-08-2025

Revised: 15-09-2025

Accepted: 28-09-2025

Published in Issue 31-12-2025

Copyright (c) 2025 Hamed Dadashi, Amirreza Nazemiyeh, Niloufar Ahdeno, Parniya Kehtari, Samar Mahari, Yadollah Omidi, Somayeh Vandghanooni, Morteza Eskandani (Author)

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This work is licensed under a Creative Commons Attribution 4.0 International License.

How to Cite

Dadashi, H., Nazemiyeh, A., Ahdeno, N., Kehtari, P., Mahari, S., Omidi, Y., Vandghanooni, S., & Eskandani, M. (2025). Chitosan Nanoparticle-Mediated Dual Delivery of Quercetin and Paclitaxel Attenuates EMT and Angiogenesis Via ZEB1 and TIMP-3 Regulation in Triple-Negative Breast Cancer. Journal of Nanostructure in Chemistry, 15(06). https://doi.org/10.57647/jnsc.2025.1506.22
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Abstract

This study investigates the therapeutic potential of chitosan nanoparticles (Cs NPs) loaded with quercetin (Que) and paclitaxel (PTX) against triple-negative breast cancer (TNBC), focusing on their impact on epithelial-mesenchymal transition (EMT), a critical driver of metastasis, using MDA-MB-231 cells in vitro and in vivo models. Characterized by an average size of 82–91 nm, a positive zeta potential (+21–27 mV), and high encapsulation efficiencies, the Cs NPs demonstrated potent anti-tumor efficacy. Que-/PTX-loaded NPs significantly enhanced in vitro cytotoxicity by inducing late apoptosis. Furthermore, they suppressed cell migration and inhibited mammosphere formation in 3D cultures, effectively countering the invasiveness associated with EMT. Notably, the NPs downregulated ZEB1, a key EMT-promoting transcription factor, and upregulated TIMP-3, an inhibitor of extracellular matrix degradation, thereby attenuating EMT-driven metastasis. The chorioallantoic membrane (CAM) assay revealed a significant reduction in angiogenesis, further supporting their anti-metastatic potential. In vivo, BALB/c nude mice with MDA-MB-231 xenografts treated with Que-/PTX-Cs NPs exhibited 71.79% tumor growth inhibition and reduced metastatic spread, with 64.27% NP accumulation in tumors. These results underscore Que-/PTX-Cs NPs as a promising nanotherapeutic strategy for TNBC, effectively targeting tumor growth, EMT-driven metastasis, and angiogenesis through ZEB1 and TIMP-3 regulation.

Keywords

  • Chitosan nanoparticles,
  • Epithelial-Mesenchymal Transition (EMT),
  • Paclitaxel,
  • Quercetin,
  • Triple-Negative Breast Cancer
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