title: Exploiting the lactose-GM3 interaction for drug delivery.
abstract: 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.
authors: Department of Chemistry, Indian Institute of Science Education and Research (IISER), Pune, Dr. Homi Bhabha Road, Pashan Pune, 411021 (India).
authors: Raghavendra Vasudeva
authors: RV
authors: Murthy
authors: Harikrishna
authors: H
authors: Bavireddi
authors: Madhuri
authors: M
authors: Gade
authors: Raghavendra
authors: R
authors: Kikkeri
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry* / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D005679:G(M3) Ganglioside / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007785:Lactose / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008968:Molecular Conformation; D041681:NIH 3T3 Cells; D013329:Structure-Activity Relationship
chemical_list: D005679:G(M3) Ganglioside; D004317:Doxorubicin; D007785:Lactose
keywords: cancer; carbohydrates; cyclodextrin; doxorubicin; host-guest complexes; targeted drug delivery