標題: Co-delivery of paclitaxel and cetuximab by nanodiamond enhances mitotic catastrophe and tumor inhibition
作者: Lin, Yu-Wei
Raj, Emmanuel Naveen
Liao, Wei-Siang
Lin, Johnson
Liu, Kuang-Kai
Chen, Ting-Hua
Cheng, Hsiao-Chun
Wang, Chi-Ching
Li, Lily Yi
Chen, Chinpiao
Chao, Jui-I
生物科技學系
分子醫學與生物工程研究所
Department of Biological Science and Technology
Institute of Molecular Medicine and Bioengineering
公開日期: 29-Aug-2017
摘要: The poor intracellular uptake and non-specific binding of anticancer drugs into cancer cells are the bottlenecks in cancer therapy. Nanocarrier platforms provide the opportunities to improve the drug efficacy. Here we show a carbon-based nanomaterial nanodiamond (ND) that carried paclitaxel (PTX), a microtubule inhibitor, and cetuximab (Cet), a specific monoclonal antibody against epidermal growth factor receptor (EGFR), inducing mitotic catastrophe and tumor inhibition in human colorectal cancer (CRC). ND-PTX blocked the mitotic progression, chromosomal separation, and induced apoptosis in the CRC cells; however, NDs did not induce these effects. Conjugation of ND-PTX with Cet (ND-PTX-Cet) was specifically binding to the EGFR-positive CRC cells and enhanced the mitotic catastrophe and apoptosis induction. Besides, ND-PTX-Cet markedly decreased tumor size in the xenograft EGFR-expressed human CRC tumors of nude mice. Moreover, ND-PTX-Cet induced the mitotic marker protein phospho-histone 3 (Ser10) and apoptotic protein active-caspase 3 for mitotic catastrophe and apoptosis. Taken together, this study demonstrated that the co-delivery of PTX and Cet by ND enhanced the effects of mitotic catastrophe and apoptosis in vitro and in vivo, which may be applied in the human CRC therapy.
URI: http://dx.doi.org/10.1038/s41598-017-09983-8
http://hdl.handle.net/11536/145981
ISSN: 2045-2322
DOI: 10.1038/s41598-017-09983-8
期刊: SCIENTIFIC REPORTS
Volume: 7
起始頁: 0
結束頁: 0
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