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dc.contributor.authorLiao, Wei-Siangen_US
dc.contributor.authorHo, Yuen_US
dc.contributor.authorLin, Yu-Weien_US
dc.contributor.authorRaj, Emmanuel Naveenen_US
dc.contributor.authorLiu, Kuang-Kaien_US
dc.contributor.authorChen, Chinpiaoen_US
dc.contributor.authorZhou, Xiao-Zhenen_US
dc.contributor.authorLu, Kun-Pingen_US
dc.contributor.authorChao, Jui-Ien_US
dc.date.accessioned2019-04-02T05:58:20Z-
dc.date.available2019-04-02T05:58:20Z-
dc.date.issued2019-03-01en_US
dc.identifier.issn1742-7061en_US
dc.identifier.urihttp://dx.doi.org/10.1016/j.actbio.2019.01.025en_US
dc.identifier.urihttp://hdl.handle.net/11536/148936-
dc.description.abstractBreast cancer is the most common malignancy and a leading cause of cancer-related mortality among women worldwide. Triple-negative breast cancer (TNBC) is characterized by the lack of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2). However, epidermal growth factor receptor (EGFR) is highly expressed in most of the TNBCs, which may provide a potential target for EGFR targeting therapy. Nanodiamond (ND) is a carbon-based nanomaterial with several advantages, including fluorescence emission, biocompatibility, and drug delivery applications. In this study, we designed a nanocomposite by using ND conjugated with paclitaxel (PTX) and cetuximab (Cet) for targeting therapy on the EGFR-positive TNBC cells. ND-PTX inhibited cell viability and induced mitotic catastrophe in various human breast cancer cell lines (MDA-MB-231, MCF-7, and BT474); in contrast, ND alone did not induce cell death. ND-PTX inhibited the xenografted human breast tumors in nude mice. We further investigated ND-PTX-Cet drug efficacy on the TNBC of MDA-MB-231 breast cancer cells. ND-PTX-Cet could specifically bind to EGFR and enhanced the anticancer effects including drug uptake levels, mitotic catastrophe, and apoptosis in the EGFR-expressed MDA-MB-231 cells but not in the EGFR-negative MCF-7 cells. In addition, ND-PTX-Cet increased the protein levels of active caspase-3 and phospho-histone H3 (Ser10). Furthermore, ND-PTX-Cet showed more effective on the reduction of TNBC tumor volume by comparison with ND-PTX. Taken together, these results demonstrated that ND-PTX-Cet nanocomposite enhanced mitotic catastrophe and apoptosis by targeting EGFR of TNBC cells, which can provide a feasible strategy for TNBC therapy. Statement of significance Current TNBC treatment is ineffective against the survival rate of TNBC patients. Therefore, the development of new treatment strategies for TNBC patients is urgently needed. Here, we have designed a nanocomposite by targeting on the EGFR of TNBC to enhance therapeutic efficacy by ND-conjugated PTX and Cet (ND-PTX-Cet). Interestingly, we found that the co-delivery of Cet and PTX by ND enhanced the apoptosis, mitotic catastrophe and tumor inhibition in the EGFR-expressed TNBC in vitro and in vivo. Consequently, this nanocomposite ND-PTX-Cet can be applied for targeting EGFR of human TNBC therapy. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.en_US
dc.language.isoen_USen_US
dc.subjectCetuximaben_US
dc.subjectEGFRen_US
dc.subjectPaclitaxelen_US
dc.subjectNanodiamonden_US
dc.subjectTriple-negative breast canceren_US
dc.titleTargeting EGFR of triple-negative breast cancer enhances the therapeutic efficacy of paclitaxel- and cetuximab-conjugated nanodiamond nanocompositeen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.actbio.2019.01.025en_US
dc.identifier.journalACTA BIOMATERIALIAen_US
dc.citation.volume86en_US
dc.citation.spage395en_US
dc.citation.epage405en_US
dc.contributor.department交大名義發表zh_TW
dc.contributor.department生物科技學系zh_TW
dc.contributor.department分子醫學與生物工程研究所zh_TW
dc.contributor.departmentNational Chiao Tung Universityen_US
dc.contributor.departmentDepartment of Biological Science and Technologyen_US
dc.contributor.departmentInstitute of Molecular Medicine and Bioengineeringen_US
dc.identifier.wosnumberWOS:000459842600032en_US
dc.citation.woscount0en_US
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