Mixed Silane Monolayers Reveal the Disparity of Biotin and Folate in Targeting Cancer Cells

Two small molecular ligands, vitamins biotin and folic acid, were used in selective targeting of cancerous cell attachment to flat surfaces. Such an approach allows assessment of the targeting effect separately from endocytosis that typically accompanies a similar analysis for targeted drug delivery systems employing nanocarriers. In both cases, mixed monolayers with a small (1%) amount of either vitamin on a long poly­(ethylene glycol) (PEG) linker with the remaining 99% covered by a short oligo­(ethylene glycol) show significant discriminative targeting with greater attachment of cancerous HeLa and MCF7 cells than noncancerous MCF10A. Beyond that, a drastically different behavior was observed for competition with free vitamins for the two scenarios: free folic acid caused inhibition of cell attachment but, surprisingly, free biotin induced anti-inhibition or enhancement of targeted cell attachment. The sodium dependence in binding to biotinylated surfaces was established, but no correlation with the potential candidates proposed in the literature, monocarboxylate transporter 1 (MCT1) and sodium mediated vitamin transporter (SMVT) proteins, was found. With nonenzymatic cell dissociation, both effects are observed even at 4 °C suggesting that the receptors are not recruited from the cytosol during cell attachment. The targeting effects are confirmed with a drug delivery formulation based on halloysite nanotubes with a hydrophobic interior and 1% PEG–Biot or 1% PEG–FA exterior modifications.