Co-delivery of paclitaxel and cetuximab by nanodiamond enhances mitotic catastrophe and tumor inhibition

Yu Wei Lin, Emmanuel Naveen Raj, Wei Siang Liao, Johnson Lin, Kuang Kai Liu, Ting Hua Chen, Hsiao Chun Cheng, Chi Ching Wang, Lily Yi Li, Chinpiao Chen, Jui-I Chao*

*此作品的通信作者

研究成果: Article同行評審

33 引文 斯高帕斯(Scopus)

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.

原文English
文章編號9814
期刊Scientific reports
7
發行號1
DOIs
出版狀態Published - 1 12月 2017

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