Abstract 3701: A targeted delivery system for anticancer drugs based on functionalized carbon nanotubes

Cancer Research(2010)

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Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Carbon nanotubes have emerged as a promising nanomaterial for the development of customizable drug delivery system due to their ability to penetrate cell membranes and to attach high loads of drugs and targeting agents on their surface. In the field of oncology, this promotes the development of therapies with improved effectivity and fewer side effects by assisting the targeting of therapeutic agents to the desired site of action. Our work focuses on the targeted delivery of the anthracycline and anthracenedione anticancer drugs doxorubicin and mitoxantrone to human colon cancer cells (WiDr) by means of a carbon nanotube-based drug delivery system. The drugs are attached to the nanotube surface in a non-covalent manner, resulting in a weight ratio (drug: CNTs) of 4:1 owing to the high surface area of CNTs. As drug binding is higher at physiological pH than at a slightly acidic pH, this method allows for the release of the drug from the nanotubes in such environments, for example late endosomes and lysosomes. In a previous study, we have shown that doxorubicin-loaded carbon nanotubes are are taken up by WiDr colon cancer cells and release their drug payload upon cellular internalization, which then translocates to the nucleus [1]. Current work is focusing on the targeting aspect: to increase the specificity of our system, we further attach a monoclonal antibody to the nanotube carrier that recognizes/binds to carcinoembryonic antigen (CEA), a target structure overexpressed by WiDr colon cancer cells. In vitro cytotoxicity studies show that the targeted drug-CNT complexes indeed have a greater therapeutic effect on WiDr cells than on MCF7 breast cancer cells, which do not express CEA. Future work will include in vivo studies on mice bearing tumor xenographs to evaluate the feasibility and behavior of our system in a setting of clinical relevance. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3701.
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