Murthy Raghavendra Vasudeva, Bavireddi Harikrishna, Gade Madhuri, Kikkeri Raghavendra
Department of Chemistry, Indian Institute of Science Education and Research (IISER), Pune, Dr. Homi Bhabha Road, Pashan Pune, 411021 (India).
ChemMedChem. 2015 May;10(5):792-6. doi: 10.1002/cmdc.201500046. Epub 2015 Mar 20.
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.
蛋白质-蛋白质和蛋白质-碳水化合物相互作用作为一种将细胞表面作为治疗应用靶点的手段已得到广泛研究。然而，碳水化合物-碳水化合物相互作用（CCIs）在很大程度上被忽视了。在此，我们研究了CCI介导的药物递送概念。评估了负载阿霉素（Dox）的乳糖功能化β-环糊精（L-β-CD）通过与细胞表面碳水化合物GM3相互作用向癌细胞进行位点特异性递送的情况。在高表达GM3的B16黑色素瘤细胞以及细胞表面缺乏GM3的急性单核细胞白血病（THP-1）细胞和小鼠成纤维细胞（NIH-3T3）中对宿主-客体复合物进行了评估。与NIH-3T3和THP-细胞相比，阿霉素（Dox）更有效地递送至B16细胞中。在用唾液酸酶或高碘酸钠预处理以阻止CCI形成的B16细胞中，药物摄取显著降低。综上所述，这些研究结果有力地支持了通过GM3-乳糖相互作用介导的CCI摄取作为可控药物递送的机制。
