Development of Antibody as Carrier incorporating Platinum-Based Agent for targeted therapy of Colorectal Cancer
Date Issued
2016
Date
2016
Author(s)
Pan, Chao-Hsuan
Abstract
Using the combination of Panitumumab, a monoclonal antibody, and oxaliplatin, a Pt-based drug, to treat patient with colorectal cancers (CRC) is known to be effective in clinical. It is thought that Panitumumab can efficiently bind to EGFR, inhibiting cell growth. Pt-based drug can cause DNA damage, inducing cell death. Synergistic effect is found when Panitumuamb and Pt-based drug are combined. However, new strategy to cure patients with CRC is to be explored. Therefore, In this study, to cure patient with EGFR-overexpressed CRC, our research team designed and created a novel nanoparticle, named Pt-Pan(N). Pt-Pan(N) is self-aggregated from Panitumumab conjugated Dichloro(1,2-diaminocyclohexane) platinum(II) (DACHPt), named Pt-Pan. It is noted that panitumumab in Pt-Pan(N) can serve as tumor-targeted drug delivery vehicles, efficiently facilitating EGFR-overexpressed CRC cells to take up Pt-based drug. After evaluation of in vitro cytotoxicity, cellular uptake and cellular binding, it is proven that Pt-Pan(N) has good ability to bind to EGFR-overexpressed colorectal cancer cells , resulting in more cancer cell death. Pt-Pan(N) could kill colorectal cancer cells more efficiently when compared with the results achieved by combination of Panitumuamb and oxaliplatin. In addition, evaluating the in vivo tumor inhibition, it is found that Pt-Pan(N) could help achieve outstanding antitumor efficacy. In sum, our findings suggest that Pt-Pan(N) could replace the use of combination of Panitumuamb and oxaliplatin and help achieve optimal anticancer efficacy for colorectal cancer treatment in clinical.
Subjects
Panitumumab
DACHPt
Oxaliplatin
colorectal cancers (CRC)
SDGs
Type
thesis