ORGN 67 |
| We launched a research program on the discovery and development of new taxane-based anticancer agents possessing tumor-targeting ability and efficacy against various cancer types, especially multi-drug resistant tumors. These new tumor-targeting anticancer agents (TTACs) are conjugates of the second-generation taxoid anticancer agents with tumor-targeting molecules through mechanism-based cleavable linkers. TTACs are specifically delivered to tumors, internalized into tumor cells, and the potent taxoid anticancer agents are released from the linker into the cytoplasm. We have successfully used monoclonal antibodies (for EGFR) and omega-3 polyunsaturated fatty acids, in particular DHA, as tumor-targeting molecules for drug conjugates, which exhibited excellent efficacy against human tumor xenografts in mouse models. We have also been exploring the use of biotin, folate, and aptamers as tumor-targeting molecules. In order to monitor and elucidate the mechanism of tumor-targeting, internalization and drug release, several fluorescent and fluorogenic probes were developed and we have successfully monitored the receptor-mediated endocytosis and drug release by means of confocal fluorescence microscopy. The use of functionalized single-wall carbon nanotubes (SWCNT) as a template for multiple warhead drug conjugates has been studied and exciting preliminary results are obtained. This lecture will summarize our approaches to efficacious tumor-targeting drug delivery using unique cleavable linkers and second-generation taxoids as the warheads. |
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New Molecular Strategies for Tumor-Targeting Drug Delivery
1:25 PM-5:20 PM, Sunday, August 19, 2007 BCEC -- 253 A/B/C, Oral
Division of Organic Chemistry |