Cyanine 5-huwentoxin-IV as a novel imaging probe to detect hNa$_v$1.7 channel overexpressed in non-small cell lung cancer
Résumé
Currently, tools for detecting cancer cells belonging to the non-small cell lung cancer (NSCLC) are lacking. As overexpression of human voltage-gated sodium channel subtype 1.7 (hNav1.7) channels was identified as a promising marker in NSCLC, we investigated whether huwentoxin-IV (HwTx-IV), known to interact preferentially with this sodium channel subtype at nanomolar concentrations, may serve as a practical tool for detecting NSCLC. To achieve this goal, we coupled HwTx-IV to the cyanine 5 fluorophore and evaluated the potential of cyanine 5-HwTx-IV (Cy5-HwTx-IV) as an imaging agent to improve the detection of this cancer type. Increased messager ribonucleic acid (mRNA) expression levels of hNav1.7 were confirmed in the A549 and H460 NSCLC cell lines, but not in the Beas-2B healthy lung cell line. Moreover, electrophysiological recordings validated the presence of functional hNav1.7 in the metastatic H460 cell line, the recorded Na+ current in this cell line being completely abolished in the presence of nanomolar concentrations of Cy5-HwTx-IV and HwTx-IV. In contrast, functional hNav1.7 was not detected in the non-metastatic A549 and healthy lung Beas-2B cell lines. Finally, confocal laser scanning microscopy allowed localisation of hNav1.7 at the plasma membranes of cells labelled with Cy5-HwTx-IV. In conclusion, this work establishes Cy5-HwTx-IV as a promising tool for NSCLC imaging, thereby enhancing diagnostic precision for this cancer type.
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