Overcoming Epithelial-Mesenchymal Transition Challenges in Cancer Detection through a Dual-Targeting Strategy.

Area of Science:

• Biotechnology
• Molecular Biology
• Cancer Research

Background:

• Epithelial cellular adhesion molecules (EpCAM) are key cancer biomarkers, but their downregulation during epithelial-mesenchymal transition (EMT) and cancer type variability limit current targeting strategies.
• Existing EpCAM-targeting technologies face challenges due to antigen expression variability and loss during EMT.

Purpose of the Study:

• To engineer a novel molecular cancer recognition probe (BAptP) for enhanced tumor targeting by simultaneously recognizing EpCAM and CD71.
• To overcome the limitations of EpCAM downregulation and variability in cancer diagnosis and therapy.

Main Methods:

• Development of bispecific aptamers (BAptP) engineered to bind to both EpCAM and CD71.
• In vitro validation of BAptP binding specificity and complex formation with various cancer cells in physiological environments.
• In vivo fluorescence imaging to assess tumor accumulation and retention of BAptP compared to monovalent aptamers.

Main Results:

• BAptP demonstrated stable binding to diverse cancer cells and formed effective targeting ligand-receptor complexes at low concentrations.
• In vitro studies confirmed specific recognition of different tumor cell types within complex biological settings.
• In vivo imaging showed superior tumor accumulation and prolonged retention of bispecific BAptP over monovalent aptamers.

Conclusions:

• The engineered bispecific aptamer probe (BAptP) offers a robust solution for recognizing cancer cells despite EpCAM expression variability.
• BAptP shows significant potential as a molecular diagnostic tool for clinical investigations.
• The enhanced tumor targeting and retention of BAptP highlight its promise for precision cancer therapy.