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2000
Volume 13, Issue 5
  • ISSN: 2211-7385
  • E-ISSN: 2211-7393

Abstract

Background

HER2-positive breast cancer is an aggressive subtype characterized by the overexpression of the HER2 receptor, a transmembrane glycoprotein critical for tumor progression. Current therapies often face challenges like drug resistance and systemic toxicity, necessitating the development of advanced drug delivery systems.

Objective

This study aimed to fabricate and determine the cytotoxicity of pH-sensitive PLA nanoparticles dual-loaded with docetaxel and each of the small molecule tyrosine kinase inhibitors (STKIs) (tucatinib, neratinib, lapatinib) in HER2-positive breast cancer cells.

Methods

Nanoparticles were synthesized by a dispersion polymerization method using an acid-labile crosslinking agent, PEG and lactide macromonomers. They were characterized for structure (TEM), surface morphology (SEM), particle size, polydispersity index, zeta potential, and drug loading capacity. Cytotoxicity was assessed on SKBR3 and MCF7 breast cancer cell lines, with IC values compared across formulations.

Results

The nanoparticles were spherical with nanoscale sizes and negative zeta potential values. studies demonstrated enhanced antiproliferative effects of the drug-loaded nanoparticles, with synergistic activity observed between docetaxel and the STKIs. The drug concentrations were halved in combination formulations and resulted in better cytotoxicity compared to single-drug treatments, particularly against SKBR3 cells. The IC values were lower in SKBR3 cells than in MCF7 cells, highlighting the role of HER2 expression in the activity of TKIs.

Conclusion

The pH-sensitive PLA nanoparticles effectively co-delivered docetaxel and STKIs and demonstrated enhanced efficacy and reduced drug dosages in HER2-positive breast cancer models. This study provides a foundation for further exploration of nanoparticle-based combination therapies with potential applications in treating other aggressive cancer types.

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/content/journals/pnt/10.2174/0122117385373466250219070753
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Nanotechnology Platform for the Delivery of Docetaxel and Tyrosine Kinase Inhibitors for HER2-Positive Breast Cancer Therapy
Pharm. Nanotechnol. 13, 1017 (2025); https://doi.org/10.2174/0122117385373466250219070753
/content/journals/pnt/10.2174/0122117385373466250219070753
/content/journals/pnt/10.2174/0122117385373466250219070753
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  • Article Type:     Research Article
Keyword(s): breast cancer; Cancer nanotechnology; combination chemotherapy; nanoparticles; site-specific drug delivery; STKIs

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