Cancer has become the leading cause of death in the U.S. for people under the age of 85. Current cancer chemotherapy relies on the premise that tumor cells are more likely to be killed by the cytotoxic agents because of their rapidly proliferating. Unfortunately, many anticancer drugs cannot differentiate normal cells from tumor cells, which would cause severe undesirable side effects. Accordingly, tumor-targeting drug delivery systems of anticancer agents have attracted extensive attention in cancer chemotherapy.

A novel molecular missile, where biotin was applied as a tumor-targeting ligand for receptor-mediated endocytosis, was explored for the efficient delivery of the anticancer agent, 2^nd-generation taxoid SB-T-1214. To further investigate the tumor-targeting process and drug release mechanism, several fluorescence-labeled drug conjugates were designed and synthesized. The cellular uptakes of these conjugates were assayed in a leukemia cancer cell line “L1210FR” by confocal fluorescence microscopy (CFM). The cytotoxicity of the tumor-targeting drug conjugate was also assayed against several different types of cells.

Additionally, single-walled carbon nanotube (SWNT) was introduced to this biotin-mediated drug delivery system. Functionalized SWNT can serve as efficient drug delivery platform for potential application to tumor-targeting chemotherapy, taking advantage of enhanced permeability and retention (EPR) effect associated with nanomaterials. We have unambiguously demonstrated the occurrence of the designed cancer-specific receptor-mediated endocytosis of the whole conjugate, followed by efficient drug release and binding of the drug to the target protein by confocal fluorescence microscopy (CFM) in the leukemia cell line “L1210FR”. The cytotoxicity of these functionalized SWNT conjugates were assayed against several different types of cells. The results have unambiguously demonstrated the occurrence of the designed cancer-specific receptor-mediated endocytosis of the whole conjugate, followed by efficient drug release and binding of the drug to the target microtubules. The conjugate shows the specificity to the cells with their surface over-expressed with the biotin receptor. The cytotoxicity of the conjugate comes from the released taxoid molecues inside the cells.