Abstract
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.
Highlights
Colorectal cancer (CRC) is one of the leading causes of morbidity and mortality worldwide[1, 2]
Epidermal growth factor receptor (EGFR) of colorectal cancer (CRC) cells is a crucial target for cancer therapy
The use of nanocarriers as drug delivery systems provide the opportunities to improve the efficacy of cancer therapy[44,45,46]
Summary
Colorectal cancer (CRC) is one of the leading causes of morbidity and mortality worldwide[1, 2]. Chemotherapeutic drugs and targeting antibodies can be used in treating CRC patients[5, 6]. Epidermal growth factor receptor (EGFR) of CRC cells is a crucial target for cancer therapy. Cetuximab (Cet) is a human/murine chimeric monoclonal antibody of EGFR with an immunoglobulin G1 Fc isotype[7] that was treated in the metastatic CRC with the EGFR expression[8]. The mitotic catastrophe in cancer cells induced by anticancer drugs contributed tumor suppression[16,17,18]. ND covalently linked with PTX was effective in drug delivery and tumor inhibition in human lung cancer[35, 40].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
