Exploiting the lactose-GM3 interaction for drug delivery.

Protein-protein and protein-carbohydrate interactions as a means to target the cell surface for therapeutic applications have been extensively investigated. However, carbohydrate-carbohydrate interactions (CCIs) have largely been overlooked. Here, we investigate the concept of CCI-mediated drug delivery. Lactose-functionalized β-cyclodextrin (L-β-CD) hosting doxorubicin (Dox) was evaluated for site-specific delivery to cancer cells via interaction with GM3 , a cell-surface carbohydrate. The host-guest complex was evaluated in B16 melanoma cells, which express exceptionally high levels of GM3 , and acute monocytic leukemia (THP-1) and mouse fibroblast (NIH-3T3) cells, which lack GM3 on the cell surface. Doxorubicin (Dox) was delivered more efficiently into B16 cells compared with NIH-3T3 and THP-1 cells. In B16 cells pretreated with sialidase or sodium periodate, thus preventing CCI formation, drug uptake was significantly decreased. Taken together, the results of these studies strongly support CCI-mediated uptake via the GM3 -lactose interaction as the mechanism of controlled drug delivery.