Development of nanodiamond-conjugated paclitaxel for drug delivery and cancer therapy

• Main Authors: Wang, Chi-Ching, 王繼慶
• Other Authors: Chao, Jui-I
• Format: Others
• Language: en_US
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/37722798632102310280

碩士 === 國立交通大學 === 生物科技學系 === 98 === Nanoparticle-conjugated anticancer drugs provide novel opportunities for cancer therapy. In this study, we evaluated nanodiamond (ND), a carbon nanomaterial, to covalently bind paclitaxel for drug delivery and cancer therapy. Paclitaxel was bound to the ND’s surface through a succession of chemical modification. Treatment with 0.1-50 μg/mL ND-paclitaxel for 48h significantly reduced the cell viability in A549 human lung cancer cells. However, ND alone or denatured ND-paclitaxel (after treatment with strong alkaline solution, 1M NaOH) did not induce the damage effects on A549 cells. The ND-paclitaxel was taken into cell and located in the microtubules and cytoplasm of A549 cells observed by confocal microscopy. Moreover, ND-paclitaxel still reserves the anticancer activity of paclitaxel. ND-paclitaxel was attributed both mitotic blockage and apoptotic induction in cancer cells. The protein levels of CDC2, phosphorylated CDC2, and cyclin B1 were decreased by treatment with ND-paclitaxel. Besides, ND-paclitaxel inhibited the tumorigenesis of xenograft human lung tumor in SCID mice. Moreover, we also found ND-paclitaxel was significantly induced cytotoxicity and apoptosis in other cancer cells including colon cancer cells (RKO and HCT116) and bladder cancer cells (BFTC 905). ND-paclitaxel induced the caspase-3 activation and the protein cleavage of PARP. In summary, we have developed a functional covalent ND-paclitaxel, which still preserves its anticancer activities on the mitotic blockage, apoptosis induction and anti-tumorigenesis.