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Selective and Synergistic Targeting of ErbB2-Positive Cancer Cells with ErbB2 Transmembrane Peptide-Ionic Liquid

Helal Abujubara1,2,3, Pankaj Bharmoria4,5, Dorota Raj6,2

  • 1Department of Chemistry and Molecular Biology, Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Natrium, Medicinaregatan 7B, Gothenburg41390, Sweden.

ACS Applied Materials & Interfaces
|August 19, 2026
PubMed

Insights

We developed a novel dual-action nanoformulation for ErbB2-positive cancers. This targeted therapy shows enhanced selectivity and potency compared to existing treatments, offering a promising new approach for aggressive tumors.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • ErbB2-positive cancers are aggressive and challenging to treat due to therapy limitations like poor selectivity and toxicity.
  • Current treatments often lack sufficient delivery mechanisms and can harm healthy tissues.
  • Developing targeted therapies is crucial for improving outcomes in ErbB2-positive cancers.

Purpose of the Study:

  • To develop a dual-action nanoformulation for selective targeting of ErbB2-positive cancer cells.
  • To combine surface-active ionic liquid (SAIL) nanocarriers with an ErbB2-derived transmembrane (TM) peptide.
  • To evaluate the efficacy and selectivity of the novel nanoformulation in preclinical cancer models.

Main Methods:

  • Synthesis and characterization of novel prolinium-based surface-active ionic liquids (SAILs) and hydrophobic TM-peptides.
  • Assembly of SAIL nanocarriers and conjugation with TM-peptides to create dual-action nanoformulations.
  • Assessment of antiproliferative activity, ErbB2 expression correlation, synergy analysis (Chou-Talalay), mechanistic studies (cellular uptake, signaling pathways), and comparative efficacy against standard chemotherapies and trastuzumab.

Main Results:

  • The V3-BAIL nanoformulation demonstrated potent antiproliferative activity specifically in ErbB2-positive cancer cell lines (breast, lung, pancreatic), with minimal effect on low-ErbB2 cells.
  • Activity strongly correlated with ErbB2 expression levels, confirming target-related selectivity.
  • Synergistic effects were observed between the SAIL nanocarrier and TM peptide.
  • V3-BAIL suppressed key cancer signaling pathways (PI3K/Akt, MAPK/ERK) and showed greater selectivity and faster action than doxorubicin, cisplatin, and trastuzumab.

Conclusions:

  • TM peptide-decorated SAIL nanocarriers represent a promising strategy for targeted cancer therapy.
  • The developed nanoformulation offers enhanced selectivity and synergistic effects for ErbB2-positive cancers.
  • This approach holds potential for improving treatment outcomes by overcoming limitations of current therapies.
Keywords:
ErbB2 cancerepidermal growth factor receptorionic liquidnanocarriertransmembrane peptide

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