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Exploiting the Lactose–GM 3 Interaction for Drug Delivery
Author(s) -
Murthy Raghavendra Vasudeva,
Bavireddi Harikrishna,
Gade Madhuri,
Kikkeri Raghavendra
Publication year - 2015
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201500046
Subject(s) - chemistry , drug delivery , doxorubicin , cancer cell , acute monocytic leukemia , lactose , sodium periodate , targeted drug delivery , cell , carbohydrate , pharmacology , biochemistry , cancer research , leukemia , cancer , biology , chemotherapy , immunology , genetics , organic chemistry
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 GM 3 , a cell‐surface carbohydrate. The host–guest complex was evaluated in B16 melanoma cells, which express exceptionally high levels of GM 3 , and acute monocytic leukemia (THP‐1) and mouse fibroblast (NIH‐3T3) cells, which lack GM 3 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 GM 3 –lactose interaction as the mechanism of controlled drug delivery.